COLUMVI- glofitamab concentrate COLUMVI- glofitamab solution, concentrate

Columvi by

Drug Labeling and Warnings

Columvi by is a Prescription medication manufactured, distributed, or labeled by Genentech, Inc., Roche Diagnostics, Genentech, Inc. (Oceanside), Roche Diagnostics GmbH, F. Hoffmann-La Roche Ltd.. Drug facts, warnings, and ingredients follow.

Drug Details [pdf]

  • BOXED WARNING (What is this?)

    WARNING: CYTOKINE RELEASE SYNDROME

    Cytokine Release Syndrome (CRS), including serious or fatal reactions, can occur in patients receiving COLUMVI. Premedicate before each dose, and initiate treatment with the COLUMVI step-up dosing schedule to reduce the risk of CRS. Withhold COLUMVI until CRS resolves or permanently discontinue based on severity [see Dosage and Administration (2.1, 2.2, 2.3, and 2.4) and Warnings and Precautions (5.1)].

  • 1 INDICATIONS AND USAGE

    COLUMVI in combination with gemcitabine and oxaliplatin is indicated for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma, not otherwise specified (DLBCL, NOS) who are not candidates for autologous stem cell transplant (ASCT).

    COLUMVI is indicated for the treatment of adult patients with relapsed or refractory DLBCL, NOS or large B-cell lymphoma (LBCL) arising from follicular lymphoma, after two or more lines of systemic therapy.

  • 2 DOSAGE AND ADMINISTRATION

    2.1 Important Dosing Information

    • Administer only as an intravenous infusion through a dedicated infusion line that includes a sterile 0.2-micron in-line filter.
    • COLUMVI should only be administered by a healthcare professional with immediate access to appropriate medical support, including supportive medications to manage severe CRS [see Dosage and Administration (2.4)].
    • Ensure adequate hydration before administering COLUMVI.
    • Premedicate before each dose [see Dosage and Administration (2.3)].
    • Following pretreatment with obinutuzumab, administer COLUMVI according to the step-up dosing schedule in Table 1 with appropriate premedication, including dexamethasone, to reduce the incidence and severity of CRS [see Dosage and Administration (2.3)].

    COLUMVI Monotherapy

    • Due to the risk of CRS, patients should be hospitalized during and for 24 hours after completion of infusion of step-up dose 1 (2.5 mg on Cycle 1 Day 8) [see Dosage and Administration (2.2) and Warnings and Precautions (5.1)].
    • Patients who experienced any grade CRS during step-up dose 1 should be hospitalized during and for 24 hours after completion of step-up dose 2 (10 mg on Cycle 1 Day 15). CRS with step-up dose 2 can occur in patients who did not experience CRS with step-up dose 1 [see Dosage and Administration (2.2) and Warnings and Precautions (5.1)].
    • For subsequent doses, patients who experienced Grade ≥ 2 CRS with their previous infusion should be hospitalized during and for 24 hours after the completion of the next COLUMVI infusion.

    COLUMVI in Combination with Gemcitabine and Oxaliplatin

    2.2 Recommended Dosage

    Pretreatment with Obinutuzumab

    Pretreat all patients with a single 1,000 mg dose of obinutuzumab administered as an intravenous infusion on Cycle 1 Day 1, 7 days prior to initiation of COLUMVI (see Table 1) to deplete the circulating and lymphoid tissue B cells.

    Obinutuzumab should be administered as an intravenous infusion at 50 mg/hour. The rate of infusion can be escalated in 50 mg/hour increments every 30 minutes to a maximum of 400 mg/hour. Refer to the obinutuzumab prescribing information for complete dosing information.

    COLUMVI Step-up Dose Schedule

    Recommended dosage for COLUMVI monotherapy

    COLUMVI dosing begins with a step-up dose schedule. Following completion of pretreatment with obinutuzumab on Cycle 1 Day 1, administer COLUMVI as an intravenous infusion according to the step-up dose schedule in Table 1. Administer premedications for each dose of COLUMVI as described in Table 4 [see Dosage and Administration (2.3)].

    Table 1: COLUMVI Monotherapy Dosing Schedule (21-Day Treatment Cycles)
    Treatment cycleDayDose of COLUMVIDuration of infusion
  • * Refer to "Pretreatment with obinutuzumab" described above.
  • † For patients who experience CRS with their previous dose of COLUMVI, the time of infusion may be extended up to 8 hours.
  • ‡ If the patient experienced CRS with the previous dose, the duration of infusion should be maintained at 4 hours.
    		•
    Cycle 1Day 1Obinutuzumab 1,000 mg*
    Day 8Step-up dose 12.5 mg4 hours†
    Day 15Step-up dose 210 mg
    Cycle 2Day 130 mg4 hours†
    Cycle 3 to 12Day 130 mg2 hours‡

    Continue COLUMVI for a maximum of 12 cycles (inclusive of Cycle 1 step-up dosing) or until disease progression or unacceptable toxicity, whichever occurs first.

    Recommended dosage for COLUMVI in combination with gemcitabine and oxaliplatin

    COLUMVI dosing begins with a step-up dose schedule. Following completion of pretreatment with obinutuzumab on Cycle 1 Day 1, administer COLUMVI as an intravenous infusion according to the step-up dose schedule in Table 2.

    COLUMVI is given in combination with gemcitabine and oxaliplatin at Cycles 1-8 and as monotherapy at Cycles 9-12. Dose schedule is shown in Table 2. Administer premedications for each dose of COLUMVI as described in Table 4 [see Dosage and Administration (2.3)].

    Table 2: COLUMVI Dosing Schedule in Combination with Gemcitabine and Oxaliplatin (21-Day Treatment Cycles)
    Treatment cycleDayDose of COLUMVI
    (duration of infusion)    		Dose of gemcitabineDose of oxaliplatin
  • * Refer to "Pretreatment with obinutuzumab" described above.
  • † Cycle 1: Gemcitabine and oxaliplatin can be administered in any order.
  • ‡ For patients who experience CRS with their previous dose of COLUMVI, the time of infusion may be extended up to 8 hours.
  • § Cycles 2-8: COLUMVI, gemcitabine and oxaliplatin can be administered in any order. Gemcitabine and oxaliplatin may be given on Day 1 or 2.
  • If the patient experienced CRS with the previous dose, the duration of infusion should be maintained at 4 hours.
    		•
    Cycle 1Day 1Obinutuzumab 1,000 mg*
    Day 2--1,000 mg/m2 †100 mg/m2 †
    Day 82.5 mg (4 hours)‡----
    Day 1510 mg (4 hours)‡
    Cycle 2Day 130 mg (4 hours)‡,§1,000 mg/m2 §100 mg/m2 §
    Cycle 3 to 8Day 130 mg (2 hours)§,1,000 mg/m2 §100 mg/m2 §
    Cycle 9 to 12Day 130 mg (2 hours)----

    Continue COLUMVI in combination with gemcitabine and oxaliplatin for 8 cycles (inclusive of Cycle 1 step-up dosing), followed by an additional 4 cycles of COLUMVI monotherapy to a maximum of 12 cycles in total or until disease progression or unmanageable toxicity, whichever occurs first.

    Monitoring for Cytokine Release Syndrome [see Warnings and Precautions (5.1)]

    • Administer the COLUMVI infusions intravenously in a healthcare setting with immediate access to medical support to manage CRS, including severe CRS.

    COLUMVI monotherapy

    • For the first COLUMVI step-up dose (2.5 mg on Cycle 1 Day 8), patients should be hospitalized during and for 24 hours after completion of the COLUMVI infusion.
    • Patients who experienced any grade CRS during step-up dose 1 should be hospitalized during and for 24 hours after completion of step-up dose 2 (10 mg on Cycle 1 Day 15). CRS with step-up dose 2 can occur in patients who did not experience CRS with step-up dose 1.
    • For subsequent infusions (30 mg on Day 1 of Cycle 2 or subsequent cycles), patients who experienced Grade ≥ 2 CRS with their previous infusion should be hospitalized during and for 24 hours after completion of the next COLUMVI infusion.

    COLUMVI in combination with gemcitabine and oxaliplatin

    • For the first COLUMVI step-up dose (2.5 mg on Cycle 1 Day 8), patients should be monitored during and after completion of the COLUMVI infusion for a combined total of 8 hours.
    • Patients who experienced Grade ≥ 2 CRS with their previous infusion should be monitored after completion of the infusion.

    Delayed or Missed Doses

    If a dose of COLUMVI is delayed, restart therapy based on the recommendations made in Table 3, then resume the treatment schedule accordingly.

    When COLUMVI is given as monotherapy, for repeat of the 2.5 mg dose patients should be hospitalized during and for 24 hours after completion of the COLUMVI infusion. For the repeat of the 10 mg dose, patients should be hospitalized during and for 24 hours after completion of the COLUMVI infusion if any grade CRS occurred during the most recent 2.5 mg dose.

    When COLUMVI is given in combination with gemcitabine and oxaplatin, for repeat of the 2.5 mg dose patients should be monitored during and after completion of the COLUMVI infusion for a combined total of 8 hours. For the repeat of the 10 mg dose, patients should be monitored after completion of the COLUMVI infusion if Grade ≥ 2 CRS occurred during the most recent 2.5 mg dose.

    Table 3: Recommendations for Restarting COLUMVI After Dose Delay
    Last Dose AdministeredTime Since Last Dose AdministeredAction for Next Dose(s)*
  • * Administer premedication as per Table 4 for all patients.
  • † Patients receiving COLUMVI monotherapy should be hospitalized during and for 24 hours after completing infusion of the 2.5 mg dose. Patients receiving Columvi in combination should be monitored during and after completing infusion of the 2.5 mg dose, for a combined total of 8 hours.
  • ‡ Patients receiving COLUMVI monotherapy should be hospitalized during and for 24 hours after completing infusion of the 10 mg dose if CRS occurred during the most recent 2.5 mg dose. Patients receiving COLUMVI in combination should be monitored after completing infusion of the 10 mg dose if Grade ≥ 2 CRS occurred during the most recent 2.5 mg dose.
    		•
    Obinutuzumab pretreatment (Cycle 1 Day 1)≤ 2 weeks
    • Administer COLUMVI 2.5 mg (Cycle 1 Day 8)†, then resume the planned treatment schedule.
    > 2 weeks
    • Repeat obinutuzumab 1,000 mg pretreatment (Cycle 1 Day 1).
    • Then administer COLUMVI 2.5 mg (Cycle 1 Day 8)† and resume the planned treatment schedule.
    COLUMVI 2.5 mg
    (Cycle 1 Day 8)    		≤ 2 weeks
    • Administer COLUMVI 10 mg (Cycle 1 Day 15)‡, then resume the planned treatment schedule.
    > 2 to ≤ 4 weeks
    • Repeat COLUMVI 2.5 mg (Cycle 1 Day 8)†.
    • Then administer COLUMVI 10 mg (Cycle 1 Day 15)‡ and resume the planned treatment schedule.
    > 4 weeks
    • Repeat obinutuzumab 1,000 mg pretreatment (Cycle 1 Day 1) and COLUMVI 2.5 mg (Cycle 1 Day 8)†.
    • Then administer COLUMVI 10 mg (Cycle 1 Day 15)‡ and resume the planned treatment schedule.
    COLUMVI 10 mg
    (Cycle 1 Day 15)    		≤ 2 weeks
    • Administer COLUMVI 30 mg (Cycle 2 Day 1), then resume the planned treatment schedule.
    > 2 to ≤ 6 weeks
    • Repeat COLUMVI 10 mg (Cycle 1 Day 15).‡
    • Then administer COLUMVI 30 mg (Cycle 2 Day 1) and resume the planned treatment schedule.
    > 6 weeks
    • Repeat obinutuzumab 1,000 mg pretreatment (Cycle 1 Day 1), COLUMVI 2.5 mg (Cycle 1 Day 8)†, and COLUMVI 10 mg (Cycle 1 Day 15)‡.
    • Then administer COLUMVI 30 mg (Cycle 2 Day 1) and resume the planned treatment schedule.
    COLUMVI 30 mg
    (Cycle 2 onwards)    		≤ 6 weeks
    • Administer COLUMVI 30 mg, then resume the planned treatment schedule.
    > 6 weeks
    • Repeat the Cycle 1 regimen described in Table 1: obinutuzumab 1,000 mg pretreatment (Day 1), COLUMVI 2.5 mg (Day 8)†, and COLUMVI 10 mg (Day 15)‡.
    • Then administer COLUMVI 30 mg (Day 1 of next cycle) and resume the planned treatment schedule.

    2.3 Recommended Premedication and Prophylactic Medications

    Premedication

    Administer the following premedications to reduce the risk of CRS and infusion-related reactions [see Warnings and Precautions (5.1)].

    Table 4: Premedications to be Administered for COLUMVI Infusion
    Day of Treatment CyclePatients requiring premedicationPremedicationAdministration
  • * If dexamethasone is not available, administer prednisone 100 mg, prednisolone 100 mg, or methylprednisolone 80 mg intravenously.
    • Cycle 1, Day 8 and Day 15; Cycle 2; Cycle 3 Dexamethasone 20 mg intravenously*Completed at least 1 hour prior to COLUMVI infusion.
    All patientsAcetaminophen 500 mg to 1,000 mg orally At least 30 minutes before COLUMVI infusion.
    Antihistamine (diphenhydramine 50 mg orally or intravenously or equivalent)Completed at least 30 minutes before COLUMVI infusion.
    All subsequent infusionsAll patients Acetaminophen 500 mg to 1,000 mg orallyAt least 30 minutes before COLUMVI infusion.
    Antihistamine (diphenhydramine 50 mg orally or intravenously or equivalent)Completed at least 30 minutes before COLUMVI infusion.
    Patients who experienced any grade CRS with the previous dose Dexamethasone 20 mg intravenously*Completed at least 1 hour prior to COLUMVI infusion.

    Tumor Lysis Syndrome Prophylaxis

    Before starting COLUMVI, administer anti-hyperuricemics to patients at risk of tumor lysis syndrome, ensure adequate hydration status, and monitor as appropriate [see Adverse Reactions (6.1)].

    Antiviral Prophylaxis

    Before starting COLUMVI, consider initiation of antiviral prophylaxis to prevent herpes virus reactivation. Consider prophylaxis for cytomegalovirus infection in patients at increased risk [see Warnings and Precautions (5.3)].

    Pneumocystis jirovecii Pneumonia (PJP)

    Consider PJP prophylaxis prior to starting COLUMVI in patients at increased risk [see Warnings and Precautions (5.3)].

    2.4 Dosage Modifications for Adverse Reactions

    No dosage reduction for COLUMVI is recommended.

    Cytokine Release Syndrome

    Identify CRS based on clinical presentation [see Warnings and Precautions (5.1)]. Evaluate for and treat other causes of fever, hypoxia, and hypotension.

    If CRS is suspected, withhold COLUMVI and manage according to the recommendations in Table 5 and current practice guidelines. Administer supportive care for CRS, which may include intensive care for severe or life-threatening cases.

    Table 5: Recommendations for Management of Cytokine Release Syndrome
    Grade*Presenting SymptomsActions
  • * American Society for Transplantation and Cellular Therapy (ASTCT) 2019 consensus grading criteria.
  • † Premedication may mask fever. Therefore if clinical presentation is consistent with CRS, follow these management guidelines.
  • ‡ Duration of infusion may be extended up to 8 hours, as appropriate for that cycle (see Table 1 and Table 2).
  • § Refer to Table 3 for information on restarting COLUMVI after dose delays [see Dosage and Administration (2.2)].
  • Low-flow oxygen defined as oxygen delivered at < 6 L/minute, high-flow oxygen defined as oxygen delivered at ≥ 6 L/minute.
    		•
    Grade 1Temperature ≥ 100.4°F (38°C)†
    • Withhold COLUMVI and manage per current practice guidelines.
      • If symptoms resolve, restart infusion at a slower rate.‡
    • Ensure CRS symptoms are resolved for at least 72 hours before next dose.§
    • Consider slower infusion rate for next dose.
    Grade 2Temperature ≥ 100.4°F (38°C)† with:
    Hypotension not requiring vasopressors
    and/or
    Hypoxia requiring low-flow oxygen by nasal cannula or blow-by
    • Withhold COLUMVI and manage per current practice guidelines.
      • If symptoms resolve, restart infusion at a slower rate.‡
    • Ensure CRS symptoms are resolved for at least 72 hours before next dose.§
    • For the next dose, consider a slower infusion rate, monitor more frequently, and consider hospitalization.
    • For recurrent Grade 2 CRS, manage per Grade 3 CRS.
    Grade 3Temperature ≥ 100.4°F (38°C)† with:
    Hypotension requiring vasopressor (with or without vasopressin)
    and/or
    Hypoxia requiring high-flow oxygen by nasal cannula, face mask, non-rebreather mask, or Venturi mask
    • Withhold COLUMVI and manage per current practice guidelines, which may include intensive care.
    • Ensure CRS symptoms are resolved for at least 72 hours before next dose.§
    • Hospitalize for the next dose, monitor more frequently, and consider a slower infusion rate.‡
    • For recurrent Grade 3 CRS, permanently discontinue COLUMVI.
    Grade 4Temperature ≥ 100.4°F (38°C)† with:
    Hypotension requiring multiple vasopressors (excluding vasopressin)
    and/or
    Hypoxia requiring oxygen by positive pressure (e.g., CPAP, BiPAP, intubation, and mechanical ventilation)
    • Permanently discontinue COLUMVI and manage per current practice guidelines, which may include intensive care.

    Neurologic Toxicity, Including ICANS

    Management recommendations for neurologic toxicity, including ICANS, is summarized in Table 6. At the first sign of neurologic toxicity, including ICANS, consider neurology evaluation and withholding COLUMVI based on the type and severity of neurotoxicity. Rule out other causes of neurologic symptoms. Provide supportive therapy, which may include intensive care.

    Table 6: Recommended Dosage Modification for Neurologic Toxicity (Including ICANS)
    Adverse ReactionSeverity*,†Actions
  • * Based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 4.03.
  • † Based on ASTCT 2019 grading for ICANS.
  • ‡ Consider the type of neurologic toxicity before deciding to withhold COLUMVI.
  • § See Dosage and Administration (2.2) on restarting COLUMVI after dose delays.
  • Evaluate benefit-risk before restarting COLUMVI.
    		•
    Grade 1
    • Continue COLUMVI and monitor neurologic toxicity symptoms.
    • If ICANS, manage per current practice guidelines.
    Grade 2
    • Withhold COLUMVI until neurologic toxicity symptoms improve to Grade 1 or baseline.‡, §
    • Provide supportive therapy, and consider neurologic evaluation.
    • If ICANS, manage per current practice guidelines.
    Neurologic Toxicity* (including ICANS†) [see Warnings and Precautions (5.2)]Grade 3
    • Withhold COLUMVI until neurologic toxicity symptoms improve to Grade 1 or baseline for at least 7 days.§,
    • For Grade 3 neurologic events lasting more than 7 days, consider permanently discontinuing COLUMVI.
    • Provide supportive therapy, and consider neurology evaluation.
    • If ICANS, manage per current practice guidelines.
    Grade 4
    • Permanently discontinue COLUMVI.
    • Provide supportive therapy, which may include intensive care, and consider neurology evaluation.
    • If ICANS, manage per current practice guidelines.

    Other Adverse Reactions

    Table 7: Recommended Dosage Modifications for Other Adverse Reactions
    Adverse Reactions*Severity*Actions
  • * Based on NCI CTCAE, version 4.03.
  • † See Dosage and Administration (2.2) on restarting COLUMVI after dose delays.
    • Infections [see Warnings and Precautions (5.3)]Grades 1 – 4
    • Withhold COLUMVI in patients with active infection until the infection resolves.†
    • For Grade 4, consider permanent discontinuation of COLUMVI.
    Grade 1
    • Monitor for signs and symptoms of compression or obstruction due to mass effect secondary to tumor flare.
    Tumor flare [see Warnings and Precautions (5.4)]Grades 2 – 4
    • Monitor for signs and symptoms of compression or obstruction due to mass effect secondary to tumor flare, and institute appropriate treatment including antihistamine and corticosteroids.
    • Withhold COLUMVI until tumor flare resolves.†
    Neutropenia
    (when COLUMVI is given as monotherapy)    		Absolute neutrophil count less than 0.5 × 109/L
    • Withhold COLUMVI until absolute neutrophil count is 0.5 × 109/L or higher.†
    Neutropenia
    (when COLUMVI is given in combination)    		Absolute neutrophil count less than 0.75 × 109/L
    • Withhold COLUMVI until absolute neutrophil count is 0.75 × 109/L or higher.†
    ThrombocytopeniaPlatelet count less than 50 × 109/L
    • Withhold COLUMVI until platelet count is 50 × 109/L or higher.†
    Other Adverse Reactions [see Adverse Reactions (6.1)]Grade 3 or higher
    • Withhold COLUMVI until the toxicity resolves to Grade 1 or baseline.†

    2.5 Preparation and Administration

    Preparation

    • Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. COLUMVI is a colorless clear solution. Discard the vial if the solution is cloudy, discolored, or contains visible particles.
    • Use aseptic technique when preparing the COLUMVI diluted solution for intravenous infusion.
    • Determine the dose, total volume of COLUMVI solution, and the number of COLUMVI vials needed (see Table 8).

    Dilution

    • Withdraw the volume of 0.9% Sodium Chloride Injection or 0.45% Sodium Chloride Injection from the infusion bag according to Table 8 and discard.
    • Withdraw the required volume of COLUMVI from vial(s) using a sterile needle and syringe and dilute into the infusion bag of 0.9% Sodium Chloride Injection or 0.45% Sodium Chloride Injection according to Table 8 to a final concentration of 0.1 mg/mL to 0.6 mg/mL. Discard any unused portion left in the vial.
    Table 8: Dilution of COLUMVI for infusion
    Dose of COLUMVISize of infusion bagVolume of 0.9% Sodium Chloride Injection or 0.45% Sodium Chloride Injection to be withdrawn and discardedVolume of COLUMVI to be added in the infusion bag
    2.5 mg50 mL27.5 mL2.5 mL
    10 mg50 mL10 mL10 mL
    100 mL10 mL10 mL
    30 mg50 mL30 mL30 mL
    100 mL30 mL30 mL
    • Gently invert infusion bag to mix the solution, in order to avoid excessive foaming. Do not shake.
    • Immediately use diluted COLUMVI solution. If not used immediately, the diluted solution can be stored:
      • Refrigerated at 2°C to 8°C (36°F to 46°F) for up to 64 hours, or
      • At room temperature up to 25°C (77°F) for up to 4 hours.
      • Do not freeze the diluted infusion solution.
      • Discard diluted infusion solution if storage time exceeds these limits.

    COLUMVI diluted with 0.9% Sodium Chloride Injection is compatible with intravenous infusion bags composed of polyvinyl chloride (PVC), polyethylene (PE), polypropylene (PP) or non-PVC polyolefin. When diluted with 0.45% Sodium Chloride Injection, COLUMVI is compatible with intravenous infusion bags composed of PVC.

    No incompatibilities have been observed with infusion sets with product-contacting surfaces of polyurethane (PUR), PVC, or PE, and in-line filter membranes composed of polyethersulfone (PES) or polysulfone.

    COLUMVI Administration

    • Administer COLUMVI as an intravenous infusion only through a dedicated infusion line that includes a sterile 0.2-micron in-line filter.
    • See Table 1 and Table 2 for duration of infusion. The maximum time for the administration of the diluted infusion solution may be extended up to 8 hours.
    • Do not mix COLUMVI with other drugs.
  • 3 DOSAGE FORMS AND STRENGTHS

    Injection:

    • 2.5 mg/2.5 mL (1 mg/mL) clear, colorless solution in a single-dose vial.
    • 10 mg/10 mL (1 mg/mL) clear, colorless solution in a single-dose vial.
  • 4 CONTRAINDICATIONS

    None.

  • 5 WARNINGS AND PRECAUTIONS

    5.1 Cytokine Release Syndrome

    COLUMVI can cause serious and fatal cytokine release syndrome (CRS) [see Adverse Reactions (6.1)].

    Administer COLUMVI in a facility equipped to monitor and manage CRS. Initiate therapy according to the COLUMVI step-up dosing schedule to reduce the risk of CRS, administer pretreatment medications, and ensure adequate hydration [Dosage and Administration (2.3)].

    At the first sign of CRS, immediately evaluate patients for hospitalization, manage per current practice guidelines, and administer supportive care; withhold or permanently discontinue COLUMVI based on severity [see Dosage and Administration (2.4)].

    In Study NP30179, among 145 patients who received COLUMVI, CRS occurred in 70%, with Grade 1 CRS developing in 52% of all patients, Grade 2 in 14%, Grade 3 in 2.8%, and Grade 4 in 1.4%. The most common manifestations of CRS included fever, tachycardia, hypotension, chills, and hypoxia.

    CRS occurred in 56% of patients after the 2.5 mg dose of COLUMVI, 35% after the 10 mg dose, 29% after the initial 30 mg target dose, and 2.8% after subsequent doses. With the first step-up dose of COLUMVI, the median time to onset of CRS (from the start of infusion) was 14 hours (range: 5 to 74 hours). CRS after any dose resolved in 98% of cases, with a median duration of first CRS of 2 days (range: 1 to 14 days). Recurrent CRS occurred in 34% of all patients. CRS can first occur with the 10 mg dose; of 135 patients treated with the 10 mg dose of COLUMVI, 15 patients (11%) experienced their first CRS event with the 10 mg dose, of which 13 events were Grade 1, 1 event was Grade 2, and 1 event was Grade 3.

    Patients should be hospitalized during and for 24 hours after completing infusion of the 2.5 mg step-up dose. Patients who experienced any grade CRS during the 2.5 mg step-up dose should be hospitalized during and for 24 hours after completion of the 10 mg step-up dose. For subsequent doses, patients who experienced Grade ≥ 2 CRS with the previous infusion should be hospitalized during and for 24 hours after the next COLUMVI infusion [see Dosage and Administration (2.1 and 2.2)].

    In STARGLO, among 172 patients who received COLUMVI in combination with gemcitabine and oxaliplatin, CRS occurred in 44%, with Grade 1 CRS developing in 31% of all patients, Grade 2 in 10%, and Grade 3 in 2.3%. The most common manifestations of CRS included pyrexia, hypotension, chills, and hypoxia.

    CRS occurred in 35% of patients after the 2.5 mg dose of COLUMVI, 14% after the 10 mg dose, 9% after the initial 30 mg target dose, and 12% after subsequent doses. With the first step-up dose of COLUMVI, the median time to onset of CRS (from the start of infusion) was 13 hours (range: 4.4 to 55 hours). The majority (14/18) of patients who experienced Grade ≥ 2 CRS had onset of CRS within 8 hours of the start of the first COLUMVI dose (2.5 mg). CRS after any dose resolved in 99% of cases, with a median duration of first CRS of 2 days (range: 1 to 19 days). Recurrent CRS occurred in 22% of all patients. CRS can first occur with the 10 mg dose; of 167 patients treated with the 10 mg dose of COLUMVI, 5 patients (3%) experienced their first CRS event with the 10 mg dose, of which all 5 events were Grade 1.

    Patients receiving COLUMVI in combination with gemcitabine and oxaliplatin should be monitored during and after completing infusion of the 2.5 mg step-up dose for a combined total of 8 hours. Patients who experienced Grade ≥ 2 CRS with the previous infusion should be monitored after completion of the infusion [see Dosage and Administration (2.1 and 2.2)].

    5.2 Neurologic Toxicity

    COLUMVI can cause serious and fatal neurologic toxicity, including Immune Effector Cell-Associated Neurotoxicity (ICANS) [see Adverse Reactions (6.1)].

    Coadministration of COLUMVI with other products that cause dizziness or mental status changes may increase the risk of neurologic toxicity. Optimize concomitant medications and hydration to avoid dizziness or mental status changes. Institute fall precautions as appropriate.

    Monitor patients for signs and symptoms of neurologic toxicity, evaluate, and provide supportive therapy; withhold or permanently discontinue COLUMVI based on severity [see Dosage and Administration (2.4)].

    Evaluate patients who experience neurologic toxicity such as tremors, dizziness, or adverse reactions that may impair cognition or consciousness promptly, including potential neurology evaluation. Advise affected patients to refrain from driving and/or engaging in hazardous occupations or activities, such as operating heavy or potentially dangerous machinery, until the neurologic toxicity fully resolves.

    In Study NP30179, among 145 patients who received COLUMVI, the most frequent neurologic toxicities of any grade were headache (10%), peripheral neuropathy (8%), dizziness or vertigo (7%), and mental status changes (4.8%, including confusional state, cognitive disorder, disorientation, somnolence, and delirium). Grade 3 or higher neurologic adverse reactions occurred in 2.1% of patients and included somnolence, delirium, and myelitis. Cases of ICANS of any grade occurred in 4.8% of patients.

    In STARGLO, among 172 patients who received COLUMVI in combination with gemcitabine and oxaliplatin, the most frequent neurologic toxicities of any grade were peripheral neuropathy (37%), insomnia (12%), headache (9%), dizziness (7%), and dysgeusia (5%). Grade 3 or higher neurologic adverse reactions occurred in 6% of patients and included peripheral sensory neuropathy, syncope, extrapyramidal disorder, confusional state, delirium, herpes zoster, meningitis aseptic, subdural hematoma, and cerebral hemorrhage. Cases of ICANS of any grade occurred in 2.3% of patients.

    5.3 Serious Infections

    COLUMVI can cause serious or fatal infections [see Adverse Reactions (6.1)].

    COLUMVI should not be administered to patients with an active infection. Administer antimicrobial prophylaxis according to guidelines. Monitor patients before and during COLUMVI treatment for infection and treat appropriately. Withhold or consider permanent discontinuation of COLUMVI based on severity [see Dosage and Administration (2.4)].

    In Study NP30179, serious infections were reported in 16% of patients, including Grade 3 or 4 infections in 10%, and fatal infections in 4.8% of patients. Grade 3 or higher infections reported in ≥ 2% of patients were COVID-19 infection (6%), including COVID-19 pneumonia, and sepsis (4.1%). Febrile neutropenia occurred in 3.4% of patients.

    In STARGLO, serious infections were reported in 23% of patients who received COLUMVI in combination with gemcitabine and oxaliplatin, including Grade 3 infections in 15%, no Grade 4 infections, and fatal infections in 3.5% of patients. Grade 3 or higher infections reported in ≥ 2% of patients were pneumonia (5%) and COVID-19 infections (4%). Febrile neutropenia occurred in 2.3% of patients.

    5.4 Tumor Flare

    COLUMVI can cause serious tumor flare [see Adverse Reactions (6.1)]. Manifestations include localized pain and swelling at the sites of the lymphoma lesions and/or dyspnea from new pleural effusions.

    Patients with bulky tumors or disease located in close proximity to airways or a vital organ should be monitored closely during initial therapy. Monitor for signs and symptoms of compression or obstruction due to mass effect secondary to tumor flare, and institute appropriate treatment. Withhold COLUMVI until tumor flare resolves [see Dosage and Administration (2.4)].

    In Study NP30179, tumor flare was reported in 12% of patients who received COLUMVI, including Grade 2 tumor flare in 4.8% of patients and Grade 3 tumor flare in 2.8%. Recurrent tumor flare occurred in two (12%) of the affected patients. Most tumor flare events occurred during Cycle 1, with a median time to first onset of 2 days (range: 1 to 16 days) after the first dose of COLUMVI. The median duration was 3.5 days (range: 1 to 35 days).

    In STARGLO, tumor flare was reported in 2.3% of patients who received COLUMVI in combination with gemcitabine and oxaliplatin. No Grade 3 or higher events were reported. Recurrent tumor flare did not occur. Only one tumor flare event occurred after COLUMVI treatment with a median time to onset of 2 days and median duration of 2 days.

    5.5 Embryo-Fetal Toxicity

    Based on its mechanism of action, COLUMVI may cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to the fetus. Advise females of reproductive potential to use effective contraception during treatment with COLUMVI and for 1 month after the last dose [see Use in Specific Populations (8.1, 8.3)].

  • 6 ADVERSE REACTIONS

    The following clinically significant adverse reactions are described elsewhere in the labeling:

    6.1 Clinical Trials Experience

    Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

    Relapsed or Refractory DLBCL, NOS or LBCL Arising from Follicular Lymphoma

    COLUMVI monotherapy

    The safety of COLUMVI was evaluated in Study NP30179, a multi-cohort, multicenter, single-arm clinical trial that included 154 adult patients with relapsed or refractory large B-cell lymphoma (LBCL) after two or more lines of systemic therapy [see Clinical Studies (14.1)]. The trial required an ECOG performance status of 0 or 1, absolute neutrophil count ≥ 1,500/µL, platelet count ≥ 75,000/µL independent of transfusion, serum creatinine ≤ 1.5 × upper limit of normal (ULN) or creatinine clearance (CrCL) ≥ 50 mL/min, and hepatic transaminases ≤ 3 × ULN. The trial excluded patients with active or previous central nervous system (CNS) lymphoma or CNS disease, acute infection, recent infection requiring intravenous antibiotics, or prior allogeneic hematopoietic stem cell transplantation (HSCT).

    Patients received pretreatment with a single dose of obinutuzumab on Day 1 of Cycle 1 (seven days prior to start of COLUMVI). Following premedication, COLUMVI was administered by intravenous infusion according to the step-up dosing schedule with 2.5 mg on Day 8 of Cycle 1, and 10 mg on Day 15 of Cycle 1. Patients received the 30 mg COLUMVI dose by intravenous infusion on Day 1 of subsequent cycles for a maximum of 12 cycles (including step-up dosing). Each cycle was 21 days. Patients were hospitalized during and for 24 hours following completion of at least the first step-up dose.

    Of the 154 patients who initiated study treatment, 145 received COLUMVI; nine patients (6%) did not receive COLUMVI due to infection, progressive disease, or patient decision. Patients received a median of 5 cycles of COLUMVI with 30% receiving all 12 cycles of COLUMVI.

    Of patients who received COLUMVI, the median age was 66 years (range: 21 to 90 years); 66% were male; 77% were White, 4.8% were Asian, 1.4% were Black or African American, 6% were Hispanic or Latino. The main diagnoses were DLBCL, NOS and LBCL arising from follicular lymphoma.

    Serious adverse reactions occurred in 48% of patients who received COLUMVI. Serious adverse reactions in ≥ 2% of patients included CRS, COVID-19 infection, sepsis, and tumor flare. Fatal adverse reactions occurred in 5% of patients from COVID-19 infection (3.4%), sepsis (1.4%), and delirium (0.6%).

    Adverse reactions led to permanent discontinuation of COLUMVI in 7% of patients, including from infection, delirium, neutropenia, and CRS. Adverse reactions led to dose interruptions of COLUMVI in 19% of patients, most frequently (≥ 2%) from neutropenia and thrombocytopenia.

    The most common (≥ 20%) adverse reactions, excluding laboratory terms, were CRS, musculoskeletal pain, rash, and fatigue. The most common Grade 3 to 4 laboratory abnormalities (≥ 20%) were lymphocyte count decreased, phosphate decreased, neutrophil count decreased, uric acid increased, and fibrinogen decreased.

    Table 9 summarizes adverse reactions observed in Study NP30179.

    Table 9: Select Adverse Reactions (≥ 10%) in Patients with Relapsed or Refractory LBCL Who Received COLUMVI in Study NP30179
    Adverse ReactionsCOLUMVI
    N=145
    All grades (%)Grade 3 or 4 (%)
    The table includes a combination of grouped and ungrouped terms. Adverse reactions were graded using NCI CTCAE version 4.03, with the exception of CRS, which was graded per ASTCT consensus criteria in most cases.
  • * Includes musculoskeletal pain, back pain, bone pain, flank pain, myalgia, neck pain, and pain in extremity.
  • † Includes fatigue and asthenia.
  • ‡ Includes edema, edema peripheral, swelling face, and face edema.
  • § Includes rash, rash pruritic, rash maculo-papular, dermatitis, dermatitis acneiform, dermatitis exfoliative, erythema, palmar erythema, pruritus, and rash erythematous.
  • Includes abdominal pain, abdominal discomfort, and abdominal pain upper.
    		•
    Immune system disorders
      Cytokine release syndrome704.1
    Musculoskeletal and connective tissue disorders
      Musculoskeletal pain*212.1
    General disorders
      Fatigue†201.4
      Pyrexia160
      Edema‡100
    Skin and subcutaneous tissue disorders
      Rash§201.4
    Gastrointestinal disorders
      Constipation140
      Diarrhea140
      Nausea100
      Abdominal pain100
    Neoplasms
      Tumor flare122.8
    Neurologic Disorders
      Headache100

    Clinically relevant adverse reactions occurring in < 10% of patients who received COLUMVI included infusion-related reaction, peripheral neuropathy, pneumonia, mental status changes, vomiting, tumor lysis syndrome, febrile neutropenia, upper respiratory tract infection, sepsis, herpes zoster infection, gastrointestinal hemorrhage, tremor, and myelitis.

    Table 10 summarizes laboratory abnormalities in Study NP30179.

    Table 10: Select Laboratory Abnormalities (≥ 20%) That Worsened from Baseline in Patients with Relapsed or Refractory LBCL Who Received COLUMVI in Study NP30179
    Laboratory AbnormalityCOLUMVI*
    All Grades (%)Grade 3 or 4 (%)
  • * The denominator used to calculate the rate varied from 137 to 145 based on the number of patients with a baseline value and at least one post-treatment value.
  • † Grade 4 neutrophil decrease occurred in 9% of patients.
    		•
    Hematology
      Lymphocytes decreased 9083
      Hemoglobin decreased728
      Neutrophils decreased5626†
      Platelets decreased568
    Chemistry
      Fibrinogen decreased8421
      Phosphate decreased 6928
      Sodium decreased497
      Calcium decreased482.1
      Gamma-glutamyl transferase increased 339
      Potassium decreased326
      Uric acid increased2323

    COLUMVI in combination with gemcitabine and oxaliplatin

    The safety of COLUMVI was evaluated in STARGLO (Study GO41944; NCT04408638), an open-label, multicenter, randomized clinical trial that included 274 patients with relapsed or refractory DLBCL, NOS [see Clinical Studies (14.2)]. The trial required an ECOG performance status of 0, 1 or 2, absolute neutrophil count ≥ 1,000/µL, platelet count ≥ 75,000/µL, CrCL ≥ 30 mL/min, and hepatic transaminases ≤ 2.5 × ULN. The trial excluded patients who received only one prior line of therapy who were candidates for stem cell transplant, patients with previous or active central nervous system lymphoma, and patients with active or recent infections.

    Patients were randomized in a 2:1 ratio to receive either COLUMVI and gemcitabine plus oxaliplatin (COLUMVI+GemOx; N=183) or rituximab and gemcitabine plus oxaliplatin (R-GemOx; N=91).

    Patients received pretreatment with a single dose of obinutuzumab on Day 1 of Cycle 1 (seven days prior to start of COLUMVI treatment schedule). Following premedication, COLUMVI was administered by intravenous infusion according to the step-up dosing schedule with 2.5 mg on Day 8 of Cycle 1 and 10 mg on Day 15 of Cycle 1. Patients received the recommended 30 mg COLUMVI dose on Day 1 of subsequent cycles to a maximum of 12 cycles in total. Gemcitabine and oxaliplatin were administered intravenously on Day 2 of Cycle 1, and then on Day 1 of subsequent cycles, for up to 8 cycles. Patients in the R-GemOx arm received R-GemOx for up to 8 cycles. Each cycle was 21 days. Patients were hospitalized at least overnight following completion of at least the first step-up dose.

    Of the 180 patients who initiated study treatment, 172 received COLUMVI+GemOx; 8 patients (1.1%) did not receive COLUMVI due to COVID-19, myocardial infection, congestive cardiac failure, progressive disease, symptomatic deterioration, patient decision, or fatal adverse events (COVID-19 and septic shock). Patients received a median of 11 cycles of COLUMVI with 44% receiving all 12 cycles of COLUMVI.

    Of patients who received COLUMVI+GemOx, the median age was 68 years (range: 22 to 88 years); 58% were male; 42% were White, 49% were Asian, 1.2% were Black or African American, 6% were Hispanic or Latino.

    Serious adverse reactions occurred in 52% of patients who received COLUMVI. Serious adverse reactions in ≥ 2% of patients included CRS, pneumonia, COVID-19, lower respiratory tract infection, diarrhoea, pyrexia, febrile neutropenia, and platelet count decreased. Fatal adverse reactions occurred in 7% of patients from COVID-19 (1.7%), pneumonitis (1.2%), acute respiratory distress syndrome (0.6%), pneumonia (0.6%), septic shock (0.6%), respiratory tract infection (0.6%), multiple organ dysfunction syndrome (0.6%), cardiac arrest (0.6%), and cerebral haemorrhage (0.6%).

    Adverse reactions led to permanent discontinuation of COLUMVI in 21% of patients, including from COVID-19, pneumonia, sepsis, and pneumonitis. Adverse reactions led to dose interruptions of COLUMVI in 44% of patients, most frequently (≥ 2%) from COVID-19, pneumonia, lower respiratory tract infection, upper respiratory tract infection, neutrophil count decreased, platelet count decreased, and neutropenia.

    The most common (≥ 20%) adverse reactions, excluding laboratory terms, were CRS, nausea, peripheral neuropathy, diarrhea, rash, pyrexia and vomiting. The most common Grade 3 to 4 laboratory abnormalities (≥ 20%) were lymphocyte count decreased, neutrophil count decreased, platelet count decreased, hemoglobin decreased, and uric acid increased.

    Table 11 summarizes the adverse reactions observed in the STARGLO study.

    Table 11: Select Adverse Reactions Occurring in ≥ 5% of Patients with Relapsed or Refractory DLBCL, NOS Receiving COLUMVI+GemOx in STARGLO
    Adverse ReactionsCOLUMVI+GemOx
    N=172    		R-GemOx
    N=88
    All grades (%)Grade 3 to 4 (%)All grades (%)Grade 3 to 4 (%)
    The table includes a combination of grouped and ungrouped terms. Adverse reactions were graded using NCI CTCAE version 4.03, with the exception of CRS, which was graded per ASTCT consensus criteria in most cases.
  • * Includes neuropathy peripheral, peripheral sensory neuropathy, paraesthesia, hypoaesthesia, dysaesthesia, peripheral motor neuropathy, and polyneuropathy.
  • † Includes rash, rash pruritic, rash maculo-papular, erythema, pruritus, rash erythematous, urticaria, and erythema multiforme.
  • ‡ Includes arthralgia, musculoskeletal pain, back pain, bone pain, myalgia, neck pain, pain in extremity, musculoskeletal chest pain, and non-cardiac chest pain.
  • § Includes COVID-19, COVID-19 pneumonia, and SARS-CoV-2 test positive.
  • Includes pneumonia, pneumonia bacterial, and pneumonia pneumococcal.
  • # Includes upper respiratory tract infection, lower respiratory tract infection, respiratory tract infection, and respiratory tract infection bacterial.
  • Þ New onset or reactivation. Includes herpes zoster, herpes virus infection.
  • ß New onset or reactivation. Includes cytomegalovirus infection, cytomegalovirus test positive, cytomegalovirus infection reactivation and cytomegalovirus viraemia.
    		•
    Immune system disorders
      Cytokine release syndrome442.300
    Nervous system disorders
      Peripheral neuropathy*371.2260
      Headache9080
    Gastrointestinal disorders
      Nausea410.6400
      Diarrhea353.5270
      Vomiting240.6220
      Constipation190160
      Abdominal pain192.34.50
    Skin and subcutaneous tissue disorders
      Rash†270.6150
    General disorders and administration site conditions
      Pyrexia240.660
    Musculoskeletal and Connective Tissue Disorder
      Muskuloskeletal pain‡192.3191.1
    Infections and infestations
      COVID-19§173.592.3
      Pneumonia135.262.3
      Respiratory infections#131.73.41.1
      Herpes viral infectionsÞ60.61.11.1
      Cytomegalovirus infectionsß60.61.11.1

    Clinically relevant adverse reactions occurring in < 5% of patients who received COLUMVI+GemOx included urinary tract infection, sepsis, ICANS, colitis, tumor flare, pancreatitis, tumor lysis syndrome, pneumonitis, tremor, candida infections, Pneumocystis jirovecii pneumonia, and borellia meningitis.

    Table 12 summarizes laboratory abnormalities in the STARGLO study.

    Table 12: Select Laboratory Abnormalities (≥ 20%) That Worsened from Baseline in Patients with Relapsed or Refractory DLBCL, NOS Who Received COLUMVI+GemOx in STARGLO
    Laboratory Abnormality*COLUMVI+GemOxR-GemOx
    All Grades (%)*Grade 3 or 4 (%)All Grades (%)Grade 3 or 4 (%)
  • * The denominator used to calculate the rate varied from 143 to 172 based on the number of patients with a baseline value and at least one post-treatment value.
  • † Grade 4 laboratory abnormalities: neutrophil decreased in 18%, lymphocytes decreased in 25%, and platelets decreased in 13%.
    		•
    Hematology
      Platelets decreased83307617 †
      Lymphocytes decreased81506125†
      Hemoglobin decreased7420448
      Neutrophil decreased65404620†
    Chemistry
      Sodium decreased451.7221.1
      Calcium decreased361.2161.1
      Albumin decreased360.6260
      Magnesium decreased240.6211.1
      Potassium decreased236101.1
      Uric acid increased22221212
  • 7 DRUG INTERACTIONS

    For certain CYP substrates where minimal concentration changes may lead to serious adverse reactions, monitor for toxicities or drug concentrations of such CYP substrates when coadministered with COLUMVI.

    Glofitamab-gxbm causes the release of cytokines [see Clinical Pharmacology (12.2)] that may suppress the activity of CYP enzymes, resulting in increased exposure of CYP substrates. Increased exposure of CYP substrates is more likely to occur after the first dose of COLUMVI on Cycle 1 Day 8 and up to 14 days after the first 30 mg dose on Cycle 2 Day 1 and during and after CRS [see Warnings and Precautions (5.1)].

    The pharmacokinetics (PK) of glofitamab-gxbm is not affected by co-administration with gemcitabine or oxaliplatin.

  • 8 USE IN SPECIFIC POPULATIONS

    8.1 Pregnancy

    Risk Summary

    Based on its mechanism of action COLUMVI may cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology (12.1)]. There are no available data on the use of COLUMVI in pregnant women to evaluate for a drug-associated risk. No animal reproductive and developmental toxicity studies have been conducted with glofitamab-gxbm.

    Glofitamab-gxbm causes T-cell activation and cytokine release; immune activation may compromise pregnancy maintenance. In addition, based on expression of CD20 on B cells and the finding of B-cell depletion in non-pregnant animals, glofitamab-gxbm can cause B-cell lymphocytopenia in infants exposed to glofitamab-gxbm in utero. Human immunoglobulin G (IgG) is known to cross the placenta; therefore, COLUMVI has the potential to be transmitted from the mother to the developing fetus. Advise women of the potential risk to the fetus.

    In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

    8.2 Lactation

    Risk Summary

    There are no data on the presence of glofitamab-gxbm in human milk or the effects on the breastfed child or milk production. Because human IgG is present in human milk, and there is potential for glofitamab-gxbm absorption leading to B-cell depletion, advise women not to breastfeed during treatment with COLUMVI and for 1 month after the last dose of COLUMVI.

    8.3 Females and Males of Reproductive Potential

    COLUMVI may cause fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1)].

    Pregnancy Testing

    Verify pregnancy status in females of reproductive potential prior to initiating COLUMVI.

    Contraception

    Females

    Advise female patients of reproductive potential to use effective contraception during treatment with COLUMVI and for 1 month after the last dose of COLUMVI [see Use in Specific Populations (8.1)].

    8.4 Pediatric Use

    The safety and efficacy of COLUMVI in pediatric patients have not been established.

    8.5 Geriatric Use

    Of the 145 patients with relapsed or refractory LBCL who received COLUMVI as monotherapy in Study NP30179, 55% were 65 years of age or older, and 23% were 75 years of age or older. There was a higher rate of fatal adverse reactions, primarily from COVID-19, in patients 65 years of age or older compared to younger patients [see Adverse Reactions (6.1)]. No overall differences in efficacy were observed between patients 65 years of age or older and younger patients.

    Of the 172 patients with relapsed or refractory DLBCL, NOS who received COLUMVI in combination with gemcitabine and oxaliplatin in STARGLO, 61% were 65 years of age or older, and 24% were 75 years of age or older. No overall differences in safety or efficacy were observed in patients 65 years of age or older compared to younger patients.

  • 11 DESCRIPTION

    Glofitamab-gxbm is a bispecific CD20-directed CD3 T-cell engager. It is a recombinant humanized anti-CD20 anti-CD3ɛ bispecific immunoglobulin G1 (IgG1) monoclonal antibody produced in Chinese hamster ovary (CHO) cells. Glofitamab-gxbm has an approximate molecular weight of 197 kDa.

    COLUMVI (glofitamab-gxbm) injection is a sterile, preservative-free, colorless, clear solution supplied in single-dose vials for intravenous infusion.

    COLUMVI is supplied in 2.5 mg/2.5 mL and 10 mg/10 mL single-dose vials at a concentration of 1 mg/mL. Each mL of solution contains 1 mg glofitamab-gxbm, histidine (0.63 mg), histidine hydrochloride monohydrate (3.34 mg), methionine (1.49 mg), polysorbate 20 (0.5 mg), sucrose (82.15 mg), and Water for Injection, USP, at pH 5.5.

  • 12 CLINICAL PHARMACOLOGY

    12.1 Mechanism of Action

    Glofitamab-gxbm is a bispecific antibody that binds to CD20 expressed on the surface of B cells, and to CD3 receptor expressed on the surface of T cells. Glofitamab-gxbm causes T-cell activation and proliferation, secretion of cytokines, and the lysis of CD20-expressing B cells. Glofitamab-gxbm showed anti-tumor activity in vivo in mouse models of DLBCL.

    12.2 Pharmacodynamics

    Circulating B Cell Count

    In Study NP30179, peripheral B cell counts decreased to undetectable levels (< 5 cells/microliter) in 86.5% of patients by Cycle 1 Day 7 after obinutuzumab pretreatment of 1,000 mg on Cycle 1 Day 1, and in 88.2% of patients by Cycle 1 Day 10 after the first glofitamab-gxbm dose of 2.5 mg on Cycle 1 Day 8.

    In STARGLO, peripheral B cell counts decreased to undetectable levels (< 5 cells/microliter) in 73.3% of patients by Cycle 1 Day 7 after obinutuzumab pretreatment of 1,000 mg on Cycle 1 Day 1.

    Cytokine Concentrations

    Plasma concentrations of cytokines (IL-2, IL-6, IL-10, TNF-α, and IFN-γ) were measured and transient elevation of cytokines was observed at doses of 0.045 mg and above. After administration of the recommended dosage of COLUMVI, the highest elevation of cytokines was generally observed within 6 hours after the first glofitamab-gxbm dose of 2.5 mg on Cycle 1 Day 8. The elevated cytokine levels generally returned to baseline within 48 hours after the first 30 mg dose on Cycle 2 Day 1.

    12.3 Pharmacokinetics

    The pharmacokinetics of glofitamab-gxbm was determined following pretreatment with a single dose of obinutuzumab of 1,000 mg and the pharmacokinetic parameters are presented as geometric mean (CV%) unless otherwise specified. Glofitamab-gxbm exposure increased dose-proportionally over the dose range from 0.005 to 30 mg (0.000167 to 1 time the recommended treatment dosage). Glofitamab-gxbm exposure parameters are summarized in Table 13 for the approved recommended dosage of COLUMVI.

    Table 13: Exposure Parameters of Glofitamab-gxbm Following Pretreatment with a Single Dose of Obinutuzumab of 1,000 mg
    AUCtau (day∙mcg/mL)Cmax (mcg/mL)Ctrough (mcg/mL)
    Data presented as geometric mean (CV%). AUCtau = area under the concentration-time curve over one 21-day cycle; Cmax = maximum glofitamab-gxbm concentration; Ctrough = glofitamab-gxbm concentration prior to next dose; CV = geometric coefficient of variation.
  • * Steady state values are approximated at Cycle 6 (week 18).
    • First full 30 mg dose45.9 (41.3%)9.42 (26.2%)0.523 (139%)
    Steady state* 30 mg dose47.2 (31.2%)9.39 (26.2%)0.562 (65.0%)

    Distribution

    The glofitamab-gxbm total volume of distribution is 5.75 L (23%).

    Elimination

    At steady state, the glofitamab-gxbm terminal half-life is 7.92 days (23.5%) and the clearance is 0.635 L/day (31.4%).

    Metabolism

    Glofitamab-gxbm is expected to be metabolized into small peptides by catabolic pathways.

    Specific Populations

    No clinically significant changes in the pharmacokinetics of glofitamab-gxbm were observed based on age (21 to 90 years), body weight (31 to 148 kg), sex, mild to moderate renal impairment (CrCL 30 to < 90 mL/min as estimated by Cockcroft-Gault formula) and mild hepatic impairment (total bilirubin > ULN to ≤ 1.5 × ULN or AST > ULN).

    The effects of severe renal impairment (CrCL 15 to < 30 mL/min), end-stage renal disease (CrCL < 15 mL/min), or moderate to severe hepatic impairment (total bilirubin > 1.5 × ULN and any AST), and race/ethnicity on the pharmacokinetics of glofitamab-gxbm are unknown.

    Drug Interaction Studies

    No clinical studies evaluating the drug interaction potential of glofitamab-gxbm have been conducted.

    12.6 Immunogenicity

    The observed incidence of antidrug antibodies (ADAs) is highly dependent on the sensitivity and specificity of the assay. Differences in assay methods preclude meaningful comparisons of the incidence of ADA in the study described below with the incidence of ADA in other studies, including those of glofitamab-gxbm.

    During treatment across studies (up to 9 months) [see Clinical Studies (14.1, 14.2)], using an enzyme-linked immunosorbent assay (ELISA), the incidence of anti-glofitamab antibody formation was 1.3% (8/608) in patients treated with COLUMVI. Because of the low occurrence of ADAs, the effect of these antibodies on the pharmacokinetics, pharmacodynamics, safety, and/or effectiveness of glofitamab-gxbm is unknown.

  • 13 NONCLINICAL TOXICOLOGY

    13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

    No carcinogenicity or genotoxicity studies have been conducted with glofitamab-gxbm.

    Fertility studies have not been conducted with glofitamab-gxbm.

  • 14 CLINICAL STUDIES

    14.1 Relapsed or Refractory DLBCL, NOS or LBCL Arising from Follicular Lymphoma

    The efficacy of COLUMVI was evaluated in Study NP30179 (NCT03075696), an open-label, multicenter, multicohort, single-arm clinical trial that included patients with relapsed or refractory LBCL after two or more lines of systemic therapy. The trial required an ECOG performance status of 0 or 1, absolute neutrophil count ≥ 1,500/µL, platelet count ≥ 75,000/µL independent of transfusion, serum creatinine ≤ 1.5 × ULN or CrCL ≥ 50 mL/min, and hepatic transaminases ≤ 3 × ULN. The trial excluded patients with active or previous CNS lymphoma or CNS disease, acute infection, recent infection requiring intravenous antibiotics, or prior allogeneic HSCT.

    Following pretreatment with obinutuzumab on Cycle 1 Day 1, patients received COLUMVI by intravenous infusion, starting with a 2.5 mg step-up dose on Cycle 1 Day 8, followed by a 10 mg step-up dose on Cycle 1 Day 15, then 30 mg on Cycle 2 Day 1 and on Day 1 of each subsequent cycle. The cycle length was 21 days. COLUMVI was administered for up to 12 cycles unless patients experienced progressive disease or unacceptable toxicity.

    The efficacy population consists of 132 patients with de novo DLBCL, NOS (80%) or LBCL arising from follicular lymphoma (20%) who received at least one dose of COLUMVI. The median age was 67 years (range: 21 to 90 years), 64% were male, 77% were White, 4.5% were Asian, 0.8% were Black or African American, 5% were Hispanic or Latino. The median number of prior lines of systemic therapy was 3 (range: 2 to 7). Most patients (83%) had refractory disease to the last therapy, 55% had primary refractory disease, 30% had received CAR T-cell therapy, and 19% had received ASCT.

    Efficacy was based on objective response rate (ORR) and duration of response (DOR), as determined by an Independent Review Committee (IRC) using the 2014 Lugano criteria.

    Efficacy results are summarized in Table 14. The median time to first response was 42 days (range: 31 to 178 days). Among responders, the estimated median follow-up for DOR was 11.6 months.

    Table 14: IRC-Assessed Efficacy in Patients with Relapsed or Refractory DLBCL, NOS or LBCL Arising from Follicular Lymphoma
    Outcome per IRCCOLUMVI
    N=132
    CI = confidence interval; NE = not estimable
  • * From date of first response (PR or CR) until disease progression or death due to any cause.
  • † Kaplan-Meier estimate.
    		•
    Overall Response Rate, n (%)74 (56)
    (95% CI)(47, 65)
      Complete Response, n (%)57 (43)
      (95% CI)(35, 52)
      Partial Response, n (%)17 (13)
      (95% CI)(8, 20)
    Duration of Response*N = 74
      Median DOR, months (95% CI)†18.4 (11.4, NE)
      9-month estimate, % (95% CI)†68.5 (56.7, 80.3)

    14.2 Relapsed or Refractory DLBCL, NOS

    The efficacy of COLUMVI was evaluated in STARGLO (Study GO41944; NCT04408638), a randomized, open-label, multicenter clinical trial that included patients with relapsed or refractory DLBCL, NOS. The trial required an ECOG performance status of 0, 1, or 2, absolute neutrophil count ≥ 1,500/µL, platelet count ≥ 75,000/µL independent of transfusion, CrCL ≥ 30 mL/min, and hepatic transaminases ≤ 2.5 × ULN. The trial excluded patients who received only one prior line of therapy who were candidates for stem cell transplant, patients with high-grade B-cell lymphoma, primary mediastinal B-cell lymphoma, history of transformation of indolent disease to DLBCL, patients with active or previous CNS lymphoma or CNS disease, patients with active or recent infections, or prior allogeneic HSCT.

    Patients were randomized 2:1 to receive COLUMVI in combination with gemcitabine and oxaliplatin (COLUMVI+GemOx) or rituximab in combination with gemcitabine and oxaliplatin (R-GemOx) for 8 cycles, followed by 4 additional cycles of COLUMVI monotherapy for patients in the COLUMVI+GemOx arm. The cycle length was 21 days. COLUMVI was administered for up to 12 cycles in total unless patients experienced progressive disease or unacceptable toxicity. Randomization was stratified by number of previous lines of systemic therapy for DLBCL (1 vs. ≥ 2) and outcome of last systemic therapy (relapsed vs. refractory).

    In the COLUMVI+GemOx arm, following pre-treatment with obinutuzumab on Cycle 1 Day 1, patients received 2.5 mg of COLUMVI on Cycle 1 Day 8, 10 mg of COLUMVI on Cycle 1 Day 15, and 30 mg of COLUMVI on Cycle 2 Day 1 as per the step-up dosing schedule. Patients continued to receive 30 mg of COLUMVI on Day 1 of Cycles 3 to 12. Gemcitabine 1000 mg/m2 and oxaliplatin 100 mg/m2 were administered intravenously on Day 2 of Cycle 1, and then on Day 1 of subsequent cycles, up to Cycle 8.

    A total of 274 patients were randomized, with 183 in the COLUMVI+GemOx arm and 91 in the R-GemOx arm. The median age was 68 years (range: 20 to 88 years), 58% were male, 42% were white, 50% were Asian, 1.1% were Black or African American, and 6% were Hispanic or Latino. A majority of patients had ECOG performance status of 1 (47%) or 2 (10%). The majority of patients (63%) had received 1 prior line of systemic therapy and 37% of patients had received 2 or more prior lines of systemic therapy. All patients had received prior chemotherapy and most (99%) had received prior anti-CD20 monoclonal antibody therapy; 8% of patients had received CAR T-cell therapy, and 4.0% had received ASCT. Overall, 56% of patients had primary refractory disease and 61% of patients were refractory to the last therapy.

    The primary endpoint was overall survival (OS). At the time of the prespecified primary analysis, a statistically significant improvement in OS was observed for patients randomized to the COLUMVI+GemOx arm compared to patients randomized to R-GemOx. Statistically significant improvements in PFS and CR rate, as assessed by IRC, were also observed with COLUMVI+GemOx over R-GemOx (Table 15).

    An updated analysis of OS, PFS, and CR conducted with an additional 10.5 months of follow-up continued to demonstrate benefit in the COLUMVI+GemOx arm (Table 15, Figure 1 and Figure 2). The 24-month OS rate was 53% [95% CI: 45, 61] in the COLUMVI+GemOx arm and 34% [95% CI: 22, 45] in the R-GemOx arm.

    Table 15: Efficacy in Patients with Relapsed or Refractory DLBCL, NOS in STARGLO
    Primary Analysis
    Median observation time=11.3 months    		Updated Analysis
    Median observation time=20.7 months
    COLUMVI+GemOx
    N=183
    		R-GemOx
    N=91    		COLUMVI+GemOx
    N=183    		R-GemOx
    N=91
    CI=confidence interval; HR=hazard ratio; NE=not estimable.
    Overall Survival
    Number (%) of deaths61 (33)40 (44)80 (44)52 (57)
    Median, months (95% CI)NE (13.8, NE)9.0 (7.3, 14.4)25.5 (18.3, NE)12.9 (7.9, 18.5)
      HR (95% CI)0.59 (0.40, 0.89)0.62 (0.43, 0.88)
      p-value0.011N/A
    Progression-free Survival- IRC-assessed
    Number (%) of patients with event68 (37)44 (48)90 (49)54 (59)
    Median, months (95% CI)12.1 (6.8, 18.3)3.3 (2.5, 5.6)13.8 (8.7, 20.5)3.6 (2.5, 7.1)
      HR (95% CI)0.37 (0.25, 0.55)0.40 (0.28, 0.57)
      p-value<0.001N/A
    Complete Response Rate- IRC-assessed
    Responders (%)92 (50)20 (22)107 (59)23 (25)
      Difference in response rate, % (95% CI)28 (16, 40)33 (21, 45)
      p-value<0.001N/A

    Figure 1: Kaplan-Meier Plot of Overall Survival (OS) in STARGLO from the Updated Analysis

    Figure 1

    Figure 2: Kaplan-Meier Plot of IRC-Assessed Progression-Free Survival (PFS) in STARGLO from the Updated Analysis

    Figure 2
  • 16 HOW SUPPLIED/STORAGE AND HANDLING

    COLUMVI (glofitamab-gxbm) injection is a sterile, preservative-free, colorless, clear solution for intravenous infusion.

    COLUMVI is supplied as:

    Carton ContentsNDC
    One 2.5 mg/2.5 mL (1 mg/mL) single-dose vialNDC: 50242-125-01
    One 10 mg/10 mL (1 mg/mL) single-dose vialNDC: 50242-127-01

    Store refrigerated at 2°C to 8°C (36°F to 46°F) in original carton to protect from light. Do not freeze. Do not shake.

  • 17 PATIENT COUNSELING INFORMATION

    Advise the patient to read the FDA-approved patient labeling (Medication Guide).

    Cytokine Release Syndrome

    Inform patients of the risk of CRS. Advise patients to seek immediate medical attention if they experience signs and symptoms of CRS (fever, hypoxia, hypotension, chills and tachycardia) [see Warnings and Precautions (5.1)].

    Provide patients with the Patient Wallet Card that they should carry with them at all times. This card describes symptoms of CRS which, if experienced, should prompt the patient to seek immediate medical attention.

    Neurologic Toxicity

    Discuss the signs and symptoms associated with neurologic toxicity, including ICANS, headache, peripheral neuropathy, dizziness, or mental status changes. Advise patients to immediately contact their healthcare provider if they experience any signs or symptoms of neurologic toxicity. Advise patients who experience neurologic toxicity that impairs consciousness to refrain from driving or operating heavy or potentially dangerous machinery until neurologic toxicity resolves [see Warnings and Precautions (5.2)].

    Serious Infections

    Advise patients that COLUMVI can cause serious infections. Advise patients to notify their healthcare provider immediately if they develop any signs of infection (e.g., fever, chills, weakness) [see Warnings and Precautions (5.3)].

    Tumor Flare

    Inform patients of the potential risk of tumor flare reaction and to report any signs and symptoms associated with this event (e.g., localized pain and swelling) to their healthcare provider for evaluation [see Warnings and Precautions (5.4)].

    Embryo-Fetal Toxicity

    Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to inform their healthcare provider if they are pregnant or become pregnant. Advise females of reproductive potential to use effective contraception during treatment with COLUMVI and for 1 month after the last dose [see Warnings and Precautions (5.5) and Use in Specific Populations (8.1, 8.3)].

    Advise women not to breastfeed while receiving treatment with COLUMVI and for 1 month after the last dose [see Use in Specific Populations (8.2)].

  • SPL UNCLASSIFIED SECTION

    COLUMVI® [glofitamab-gxbm]

    Manufactured by:
    Genentech, Inc.
    A Member of the Roche Group
    1 DNA Way
    South San Francisco, CA 94080-4990

    U.S. License No.: 1048

    COLUMVI® is a registered trademark of
    Genentech, Inc.

    ©202X Genentech, Inc. All rights reserved.

  • MEDICATION GUIDE

    MEDICATION GUIDE
    COLUMVI® (ko-loom-vee)
    (glofitamab-gxbm)
    injection, for intravenous infusion
    This Medication Guide has been approved by the U.S. Food and Drug Administration.Issued: X/XXXX

    What is the most important information I should know about COLUMVI?

    COLUMVI can cause Cytokine Release Syndrome (CRS), a serious side effect that is common during treatment with COLUMVI, and can also be serious and lead to death.
    • Call your healthcare provider or get emergency medical help right away if you develop any signs or symptoms of CRS, including:
    • fever of 100.4°F (38°C) or higher
    • chills or shaking
    • fast or irregular heartbeat
    • dizziness or light-headedness
    • trouble breathing
    • shortness of breath
    • Due to the risk of CRS, you will receive COLUMVI on a "step-up dosing schedule".
      • A single dose of a medicine called obinutuzumab will be given to you on the first day of your first treatment cycle (Day 1 of Cycle 1).
      • You will start the COLUMVI step-up dosing schedule a week after the obinutuzumab dose. The step-up dosing schedule is when you receive smaller "step-up" doses of COLUMVI on Day 8 and Day 15 of Cycle 1. This is to help reduce your risk of CRS.
        • When Columvi is given alone, you should be hospitalized during your infusion and for 24 hours after receiving the first step-up dose on Day 8. You should be hospitalized during your infusion and for 24 hours after receiving the second step-up dose on Day 15 if you experienced CRS during the first step-up dose.
        • When Columvi is given with the medicines gemcitabine and oxaliplatin, you should be monitored during and after the first step-up dose on Day 8 for a combined total of 8 hours. You should be monitored after after receiving the second step-up dose on Day 15 if you experienced Grade ≥ 2 during the first step-up dose.
      • You will receive your first full dose of COLUMVI a week after the second step-up dose (this will be Day 1 of Cycle 2).
      • If your dose of COLUMVI is delayed for any reason, you may need to repeat the "step-up dosing schedule".
      • When Columvi is given alone, if you had more than mild CRS with your previous dose of COLUMVI, you should be hospitalized for 24 hours after receiving your next dose of COLUMVI.
      • Before each dose of COLUMVI, you will receive medicines to help reduce your risk of CRS and infusion-related reactions.
      • See "How will I receive COLUMVI?" for more information about how you will receive COLUMVI.
    • Your healthcare provider will monitor you for CRS during treatment with COLUMVI and may treat you in a hospital if you develop signs and symptoms of CRS. Your healthcare provider may temporarily stop or completely stop your treatment with COLUMVI if you have severe side effects.
    • Carry the COLUMVI Patient Wallet Card with you at all times and show it to all of your healthcare providers. The COLUMVI Patient Wallet Card lists the signs and symptoms of CRS you should get emergency medical help for right away.
    See "What are the possible side effects of COLUMVI?" for more information about side effects.
    What is COLUMVI?
    COLUMVI is a prescription medicine used:
    • alone to treat adults with certain types of diffuse large B-cell lymphoma (DLBCL) or large B-cell lymphoma (LBCL) that has come back (relapsed) or that did not respond to previous treatment (refractory), and who have received 2 or more prior treatments for their cancer.
    • with the medicines gemcitabine and oxaliplatin to treat adults with diffuse large B-cell lymphoma (DLBCL) that has come back (relapsed) or that did not respond to previous treatment (refractory), and who cannot receive a stem cell transplant.
    It is not known if COLUMVI is safe and effective in children.
    Before receiving COLUMVI, tell your healthcare provider about all of your medical conditions, including if you:
    • have an infection
    • have kidney problems
    • are pregnant or plan to become pregnant. COLUMVI may harm your unborn baby.
      Females who are able to become pregnant:
      • Your healthcare provider should do a pregnancy test before you start treatment with COLUMVI.
      • You should use effective birth control (contraception) during treatment and for 1 month after your last dose of COLUMVI. Talk to your healthcare provider about what birth control method is right for you during this time.
      • Tell your healthcare provider right away if you become pregnant or think you may be pregnant during treatment with COLUMVI.
    • are breastfeeding or plan to breastfeed. It is not known if COLUMVI passes into your breastmilk. Do not breastfeed during treatment and for 1 month after your last dose of COLUMVI.
    Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

    How will I receive COLUMVI?

    • COLUMVI will be given to you by your healthcare provider by infusion through a needle placed in your vein (intravenous infusion).
    • Your COLUMVI treatment schedule is divided into cycles that are 21 days (3 weeks) long.
    • On Day 1 of Cycle 1, your healthcare provider will give you a single dose of a medicine called obinutuzumab by intravenous infusion. You will then receive COLUMVI on Day 8 and Day 15 of Cycle 1. Starting with Cycle 2, you will receive COLUMVI 1 time every three weeks.
    Your healthcare provider will decide how many treatment cycles you will receive of COLUMVI. See "What is the most important information I should know about COLUMVI?" for more information about how you will receive COLUMVI.
    What should I avoid while receiving COLUMVI?
    Do not     drive, operate heavy machinery, or do other dangerous activities if you develop dizziness, confusion, shaking (tremors), sleepiness, or any other symptoms that impair consciousness until your signs and symptoms go away. These may be signs and symptoms of neurologic problems.
    See "What are the possible side effects of COLUMVI?" for more information about signs and symptoms of neurologic problems.

    What are the possible side effects of COLUMVI?

    COLUMVI may cause serious side effects, including:
    • Cytokine Release Syndrome. See "What is the most important information I should know about COLUMVI?"
    • Neurologic problems. COLUMVI can cause serious neurologic problems that may lead to death. Your healthcare provider will monitor you for neurologic problems during treatment with COLUMVI. Your healthcare provider may also refer you to a healthcare provider who specializes in neurologic problems. Tell your healthcare provider right away if you develop any signs or symptoms of neurologic problems, including:
    • headache
    • confusion and disorientation
    • difficulty paying attention or understanding things
    • trouble speaking
    • sleepiness
    • memory problems
    • numbness, tingling, or weakness of the hands or feet
    • dizziness
    • shaking (tremors)
    • Serious infections. COLUMVI can cause serious infections that may lead to death. Your healthcare provider will monitor you for signs and symptoms of infection and treat you as needed. Tell your healthcare provider right away if you develop any signs of infection, including: fever, chills, weakness, cough, shortness of breath, or sore throat.
    • Growth in your tumor or worsening of tumor related problems (tumor flare). Tell your healthcare provider if you get any of these signs or symptoms of tumor flare:
      • tender or swollen lymph nodes
      • pain or swelling at the site of the tumor
      • chest pain
      • cough
      • trouble breathing
    Your healthcare provider may temporarily stop or completely stop treatment with COLUMVI if you develop certain side effects.
    The most common side effects of COLUMVI when used alone include: CRS, muscle and bone pain, rash, and tiredness.
    The most common side effects of COLUMVI when used with other anti-cancer medicines include: CRS, nausea, numbness, tingling, or weakness of the hands or feet, diarrhea, rash, fever, and vomiting.
    The most common severe abnormal lab test results with COLUMVI when used alone include: decreased white blood cells, decreased phosphate (an electrolyte), increased uric acid levels, and decreased fibrinogen (a protein that helps with blood clotting).
    The most common severe abnormal lab test results with COLUMVI when used with other anti-cancer medicines include: decreased white blood cells, decreased platelet cells, decreased red blood cells, and increased uric acid levels.
    These are not all the possible side effects of COLUMVI.
    Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
    General information about the safe and effective use of COLUMVI.
    Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. You can ask your healthcare provider or pharmacist for information about COLUMVI that is written for health professionals.
    What are the ingredients in COLUMVI?
    Active ingredient:     glofitamab-gxbm
    Inactive ingredients: histidine, histidine hydrochloride monohydrate, methionine, polysorbate 20, sucrose, and Water for injection.
    Manufactured by: Genentech, Inc., A Member of the Roche Group, 1 DNA Way, South San Francisco, CA 94080-4990
    U.S. License No.: 1048
    For more information, go to www.COLUMVI.com or call 1-877-436-3683.
  • PRINCIPAL DISPLAY PANEL - 10 mg/10 mL Vial Carton

    NDC: 50242-127-01

    Columvi™

    (glofitamab-gxbm)
    Injection

    10 mg/10 mL
    (1 mg/mL)

    For Intravenous Infusion
    After Dilution.

    Single-Dose Vial.
    Discard Unused Portion.

    ATTENTION: Dispense the enclosed
    Medication Guide to each patient.

    Rx only

    1 vial
    Genentech

    10252990

    PRINCIPAL DISPLAY PANEL - 10 mg/10 mL Vial Carton
  • PRINCIPAL DISPLAY PANEL - 2.5 mg/2.5 mL Vial Carton

    NDC: 50242-125-01

    Columvi™

    (glofitamab-gxbm)
    Injection

    2.5 mg/2.5 mL
    (1 mg/mL)

    For Intravenous Infusion
    After Dilution.

    Single-Dose Vial.
    Discard Unused Portion.

    ATTENTION: Dispense the enclosed
    Medication Guide to each patient.

    Rx only

    1 vial
    Genentech

    10252987

    PRINCIPAL DISPLAY PANEL - 2.5 mg/2.5 mL Vial Carton
  • INGREDIENTS AND APPEARANCE
    COLUMVI 
    glofitamab concentrate
    Product Information
    Product TypeHUMAN PRESCRIPTION DRUGItem Code (Source)NDC: 50242-127
    Route of AdministrationINTRAVENOUS
    Active Ingredient/Active Moiety
    Ingredient NameBasis of StrengthStrength
    GLOFITAMAB (UNII: 06P3KLK2J8) (GLOFITAMAB - UNII:06P3KLK2J8) GLOFITAMAB10 mg  in 10 mL
    Inactive Ingredients
    Ingredient NameStrength
    HISTIDINE (UNII: 4QD397987E) 6.3 mg  in 10 mL
    HISTIDINE MONOHYDROCHLORIDE MONOHYDRATE (UNII: X573657P6P) 33.4 mg  in 10 mL
    METHIONINE (UNII: AE28F7PNPL) 14.9 mg  in 10 mL
    SUCROSE (UNII: C151H8M554) 821.5 mg  in 10 mL
    POLYSORBATE 20 (UNII: 7T1F30V5YH) 5 mg  in 10 mL
    Packaging
    #Item CodePackage DescriptionMarketing Start DateMarketing End Date
    1NDC: 50242-127-011 in 1 CARTON06/15/2023
    110 mL in 1 VIAL, SINGLE-DOSE; Type 0: Not a Combination Product
    Marketing Information
    Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
    BLABLA76130906/15/2023
    COLUMVI 
    glofitamab solution, concentrate
    Product Information
    Product TypeHUMAN PRESCRIPTION DRUGItem Code (Source)NDC: 50242-125
    Route of AdministrationINTRAVENOUS
    Active Ingredient/Active Moiety
    Ingredient NameBasis of StrengthStrength
    GLOFITAMAB (UNII: 06P3KLK2J8) (GLOFITAMAB - UNII:06P3KLK2J8) GLOFITAMAB2.5 mg  in 2.5 mL
    Inactive Ingredients
    Ingredient NameStrength
    HISTIDINE (UNII: 4QD397987E) 1.6 mg  in 2.5 mL
    HISTIDINE MONOHYDROCHLORIDE MONOHYDRATE (UNII: X573657P6P) 8.4 mg  in 2.5 mL
    METHIONINE (UNII: AE28F7PNPL) 3.7 mg  in 2.5 mL
    SUCROSE (UNII: C151H8M554) 205.4 mg  in 2.5 mL
    POLYSORBATE 20 (UNII: 7T1F30V5YH) 1.25 mg  in 2.5 mL
    WATER (UNII: 059QF0KO0R)  
    Packaging
    #Item CodePackage DescriptionMarketing Start DateMarketing End Date
    1NDC: 50242-125-011 in 1 CARTON06/15/2023
    12.5 mL in 1 VIAL, SINGLE-DOSE; Type 0: Not a Combination Product
    Marketing Information
    Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
    BLABLA76130906/15/2023
    Labeler - Genentech, Inc. (080129000)
    Registrant - Roche Diagnostics (323105205)
    Establishment
    NameAddressID/FEIBusiness Operations
    Roche Diagnostics323105205ANALYSIS(50242-125, 50242-127) , API MANUFACTURE(50242-125, 50242-127)
    Establishment
    NameAddressID/FEIBusiness Operations
    Genentech, Inc.080129000ANALYSIS(50242-125, 50242-127) , MANUFACTURE(50242-125, 50242-127) , PACK(50242-125, 50242-127) , LABEL(50242-125, 50242-127)
    Establishment
    NameAddressID/FEIBusiness Operations
    Genentech, Inc. (Oceanside)146373191ANALYSIS(50242-125, 50242-127)
    Establishment
    NameAddressID/FEIBusiness Operations
    Roche Diagnostics GmbH315028860ANALYSIS(50242-125, 50242-127)
    Establishment
    NameAddressID/FEIBusiness Operations
    F. Hoffmann-La Roche Ltd.485244961LABEL(50242-125, 50242-127) , PACK(50242-125, 50242-127)

    • Trademark Results [Columvi]

    Mark Image

    Registration | Serial
    Company
    Trademark
    Application Date
    COLUMVI
    COLUMVI
    97888709 not registered Live/Pending
    Genentech, Inc.
    2023-04-14
    COLUMVI
    COLUMVI
    88925128 not registered Live/Pending
    Genentech, Inc.
    2020-05-20
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