TZIELD

WARNING: Viral Reactivation Serious, life-threatening cases of viral reactivation, including Epstein-Barr virus (EBV) and cytomegalovirus (CMV) reactivation have been reported with TZIELD. Patients who are immunocompromised are at increased risk. Serious cases have also been reported in adults with higher body surface area or comorbid conditions, such as adrenal insufficiency or cardiovascular disease. The majority of serious cases occurred in patients who continued TZIELD treatment despite persistent, severe lymphopenia. Severe lymphopenia may be prolonged in adults. ( 5.1 , 5.4 ) Test patients for active EBV and CMV infection prior to starting treatment. TZIELD is contraindicated in patients who are immunocompromised or have active viral infection (such as EBV or CMV infection). Adhere to lymphocyte count monitoring requirements and discontinuation recommendations. Monitor patients for signs and symptoms of viral reactivation following TZIELD treatment and for at least 2 months following the last infusion. If viral reactivation is suspected, discontinue TZIELD. ( 2.6 , 4 , 5.1 , 5.4 ) WARNING: Viral Reactivation Serious, life-threatening cases of viral reactivation, including Epstein-Barr virus (EBV) and cytomegalovirus (CMV) reactivation have been reported with TZIELD. Patients who are immunocompromised are at increased risk. Serious cases have also been reported in adults with higher body surface area or comorbid conditions, such as adrenal insufficiency or cardiovascular disease. The majority of serious cases occurred in patients who continued TZIELD treatment despite persistent, severe lymphopenia. Severe lymphopenia may be prolonged in adults. ( 5.1 , 5.4 ) Test patients for active EBV and CMV infection prior to starting treatment. TZIELD is contraindicated in patients who are immunocompromised or have active viral infection (such as EBV or CMV infection). Adhere to lymphocyte count monitoring requirements and discontinuation recommendations. Monitor patients for signs and symptoms of viral reactivation following TZIELD treatment and for at least 2 months following the last infusion. If viral reactivation is suspected, discontinue TZIELD. ( 2.6 , 4 , 5.1 , 5.4 )

5 WARNINGS AND PRECAUTIONS Cytokine Release Syndrome (CRS): Premedicate, monitor liver enzymes and bilirubin during treatment, and discontinue in those that develop elevated ALT or AST more than 5 times the upper limit of normal (ULN) or bilirubin more than 3 times ULN. If severe CRS develops, consider temporarily pausing or discontinuing TZIELD. ( 5.2 ). Serious Infections: Use of TZIELD is not recommended in patients with active serious infection or chronic infection. Monitor for signs and symptoms of infection during and after TZIELD treatment. If a serious infection develops, discontinue TZIELD ( 5.3 ). Lymphopenia: Monitor lymphocyte counts during the treatment period. If prolonged severe lymphopenia (<500 cells per mcL lasting 1 week or longer) develops, discontinue TZIELD ( 5.4 ). Hypersensitivity Reactions: If severe hypersensitivity reactions occur, discontinue TZIELD and treat promptly ( 5.5 ). Vaccinations: Administer all age-appropriate vaccinations prior to starting TZIELD. See the full PI for recommendations regarding live-attenuated, inactivated, and mRNA vaccines ( 5.6 ). 5.1 Viral Reactivation Serious, life-threatening cases of viral reactivation, including EBV and CMV infections, have been reported with TZIELD. During and within 2 months of TZIELD treatment, if primary infection or reactivation of EBV or CMV occurs, it may present with increased severity, including EBV-associated lymphoproliferative disease and organ failure. Patients who are immunocompromised, including patients with Down syndrome, may be at increased risk. TZIELD is contraindicated in patients who are immunocompromised or have active viral infection (such as EBV or CMV infection). The majority of serious viral reactivation cases occurred in patients who continued TZIELD despite persistent, severe lymphopenia. The duration of severe lymphopenia following TZIELD treatment may be prolonged in adults [see Warnings and Precautions (5.4) ]. Serious cases have also been reported in adults with higher body surface area or comorbid conditions, such as adrenal insufficiency or cardiovascular disease. Prior to initiating treatment with TZIELD, evaluate patients for active EBV and CMV infection and confirm absence of active infection on assessment of viral load (e.g., PCR). TZIELD is contraindicated in patients who are immunocompromised or have active viral infection (such as EBV or CMV infection) [see Dosage and Administration (2.2) ]. During treatment with TZIELD, regularly monitor lymphocyte counts [see Dosage and Administration (2.6) , Warnings and Precautions (5.4) ] and monitor patients for signs and symptoms of viral reactivation during treatment and for at least 2 months following the last infusion. If viral reactivation is suspected, discontinue TZIELD and obtain viral load (e.g., PCR) promptly. Consider appropriate expert consultation for diagnostic testing recommendations as some diagnostic tests may give inaccurate results following treatment with TZIELD, including rapid heterophile antibody testing. If viral reactivation is confirmed, permanently discontinue TZIELD [see Dosage and Administration (2.6) ]. Consider appropriate expert consultation for the management of severe viral reactivation. 5.2 Cytokine Release Syndrome Cytokine release syndrome (CRS) has been observed in TZIELD-treated patients. In a pool of clinical trials, CRS was reported in 5% of TZIELD-treated patients compared to 0.8% of control-treated patients. In the PROTECT study, CRS was reported in 9% of TZIELD-treated patients compared to 1% of placebo-treated patients during the treatment period and through 28 days after the last study drug administration. Manifestations of CRS in TZIELD-treated patients included fever, nausea (with or without vomiting), fatigue, headache, myalgia, arthralgia, increased ALT, increased AST, and increased total bilirubin. These manifestations typically occurred during the first 5 days of TZIELD treatment [see Adverse Reactions (6.1) ] . To mitigate CRS: Premedicate with antipyretics, antihistamines and/or antiemetics prior to TZIELD treatment [see Dosage and Administration (2.3) ]. Monitor liver enzymes and bilirubin during treatment. Discontinue TZIELD treatment in patients who develop elevated ALT or AST more than 5 times the upper limit of normal (ULN) or bilirubin more than 3 times ULN. Treat symptoms of CRS in TZIELD-treated patients with antipyretics, antihistamines and/or antiemetics. If severe CRS develops, consider: Temporarily pausing TZIELD dosing for 1–2 days and if symptoms have resolved or significantly improved, subsequently administering the remaining doses on consecutive days to complete the full 14-day treatment course in patients with Stage 2 T1D or each of the two 12-day courses in patients with Stage 3 T1D, or Discontinuing TZIELD treatment . 5.3 Serious Infections Bacterial and viral infections have occurred in TZIELD-treated patients. In a pool of clinical trials, TZIELD-treated patients had a higher rate of serious infections (3.5%) than control-treated patients (2%), including gastroenteritis, cellulitis, pneumonia, abscess, sepsis [see Adverse Reactions (6.1) ]. Adults may have a longer duration of severe lymphopenia following TZIELD treatment, which may increase the risk for serious infections. Use of TZIELD is not recommended in patients with active serious infection, or chronic infection other than localized skin infections. Monitor patients for signs and symptoms of infection during and after TZIELD treatment. If serious infection develops, treat appropriately, and discontinue TZIELD. 5.4 Lymphopenia In a pool of clinical trials, 78% of TZIELD-treated patients developed lymphopenia compared to 11% of control-treated patients. For most TZIELD-treated patients who experienced lymphopenia, lymphocyte levels began to recover after the fifth day of treatment and returned to pre-treatment values within two weeks after treatment completion and without dose interruption. Severe lymphopenia (<500 cells per mcL) lasting 1 week or longer occurred in 0.9% of TZIELD-treated patients, 0.5% of TZIELD-treated patients permanently discontinued TZIELD because of lymphopenia [see Adverse Reactions (6.1) ]. In the PROTECT study, 51% of TZIELD-treated patients developed lymphopenia compared to 3% of placebo-treated patients. Severe lymphopenia lasting 1 week or longer occurred in 1.4% of TZIELD-treated patients [see Adverse Reactions (6.1) ]. Severe lymphopenia following TZIELD treatment may be more prolonged in adults. Obtain a CBC prior to starting TZIELD and monitor lymphocyte counts during TZIELD treatment. If prolonged severe lymphopenia (<500 cells per mcL lasting 1 week or longer) develops, permanently discontinue TZIELD. 5.5 Hypersensitivity Reactions Acute hypersensitivity reactions including serum sickness, angioedema, urticaria, rash, vomiting and bronchospasm occurred in TZIELD-treated patients [see Adverse Reactions (6.1) ]. If severe hypersensitivity reactions occur, discontinue use of TZIELD and treat promptly. 5.6 Vaccinations The safety of immunization with live-attenuated vaccines in TZIELD-treated patients has not been studied. Additionally, TZIELD may interfere with the immune response to vaccination and decrease vaccine efficacy. Administer all age-appropriate vaccinations prior to starting TZIELD [see Dosage and Administration (2.2) ]. Inactivated or mRNA vaccinations are not recommended within the 2 weeks prior to any TZIELD treatment course, during treatment, or up to 6 weeks after completion of any treatment course. Live-attenuated vaccinations are not recommended within the 8 weeks prior to starting TZIELD treatment, during treatment, between treatment courses, or up to 52 weeks after completion of final treatment course.

6 ADVERSE REACTIONS The following serious adverse reactions are described elsewhere in the Prescribing Information: Viral Reactivation [see Warnings and Precautions (5.1) ] Cytokine Release Syndrome [see Warnings and Precautions (5.2) ] Serious Infections [see Warnings and Precautions (5.3) ] Lymphopenia [see Warnings and Precautions (5.4) ] Hypersensitivity Reactions [see Warnings and Precautions (5.5) ] Most common adverse reactions were lymphopenia, vomiting, rash, leukopenia, diarrhea, neutropenia, increased liver transaminase and headache ( 6.1 ). To report SUSPECTED ADVERSE REACTIONS, contact Provention Bio, Inc. at 1-800-633-1610 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch 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. Placebo-Controlled Study in Adult and Pediatric Patients Aged 8 Years and Older with Stage 2 T1D (TN-10) The data in Table 2 are derived from the placebo-controlled study (Study TN-10) in adult and pediatric patients aged 8 years and older with Stage 2 T1D [see Clinical Studies (14.1) ]. These data reflect exposure of 44 patients of whom 93% completed the full 14-day treatment course. Table 2 presents common (≥5%) adverse reactions that occurred during treatment and through 28 days after the last study drug administration in patients with Stage 2 T1D in Study TN-10. Adverse reactions observed in pediatric patients 8 years and older who received TZIELD were consistent with those reported in adult patients in this study. Table 2. Common Adverse Reactions That occurred during treatment and through 28 days after the last study drug administration. in Adult and Pediatric Patients Aged 8 Years and Older with Stage 2 T1D (Study TN-10) Adverse reactions that occurred in 2 or more TZIELD-treated patients Adverse Reaction TZIELD N=44 Placebo N=32 Lymphopenia Grouped term includes other related terms 73% 6% Rash 36% 0% Leukopenia 21% 0% Headache 11% 6% Neutropenia 5% 3% Increased alanine aminotransferase 5% 3% Nausea 5% 3% Diarrhea 5% 0% Nasopharyngitis 5% 0% Placebo-Controlled Trial in Pediatric Patients Aged 8 to 17 Years with Stage 3 T1D In a 78-week placebo-controlled trial (PROTECT) in patients aged 8 to 17 years recently diagnosed with Stage 3 T1D, 328 patients were randomized to TZIELD or placebo daily by intravenous infusion for a 12-day course followed by another 12-day course 6 months later [see Clinical Studies (14.2) ]. Table 3 presents common adverse reactions (≥5%) that occurred during either of the two 12-day treatment courses and through 28 days after the last dose of study drug administration in the PROTECT trial. Table 3. Common Adverse Reactions Adverse reactions occurring in equal or more than 5% of participants in the TZIELD group, higher in TZIELD compared to placebo, in treatment course 1 through 28 days after the last dose. in Pediatric Patients Aged 8 to 17 Years with Stage 3 T1D (PROTECT Study) Adverse Reaction TZIELD n=217 Placebo n=111 Course 1 Lymphopenia Grouped term includes other related terms. 51% 3% Rash 51% 9% Leukopenia 34% 3% Nausea 34% 12% Headache 29% 16% Vomiting 26% 5% Neutropenia 23% 5% Abdominal pain 18% 11% Pyrexia 16% 3% Alanine aminotransferase increased 11% 0% Diarrhea 10% 6% Cytokine release syndrome 7% 1% Hypotension 7% 6% Aspartate aminotransferase increased 7% 1% Hemoglobin decreased 5% 4% Chills 5% 0% No new adverse reactions were observed with the second course of TZIELD treatment. Incidence rates were similar than those reported during the first treatment course. Pool of Five Controlled Clinical Studies in Stage 2 or Stage 3 T1D Adverse reactions in TZIELD-treated patients were also evaluated in a larger pool of adult and pediatric patients who participated in five controlled clinical studies (including Study TN-10 described above): One study in patients with Stage 2 T1D (Study TN-10) [see Clinical Studies (14.1) ] , Three placebo-controlled studies in patients with Stage 3 T1D, One open-label standard-of-care controlled study of TZIELD in patients with Stage 3 T1D. In this pool: 773 patients received TZIELD (44 patients with Stage 2 T1D and 729 patients with Stage 3 T1D), and 245 patients received either placebo or standard of care control (32 patients with Stage 2 T1D and 213 patients with Stage 3 T1D). In these studies, 436 patients received a 14-day dosing regimen of TZIELD with a total drug exposure that was comparable to the total drug exposure achieved with the recommended dosage [see Dosage and Administration (2.4) ] , 168 patients received a 14-day course of TZIELD with a lower total TZIELD drug exposure, and 169 patients received a 6-day course of TZIELD with a lower total TZIELD drug exposure. The mean age of TZIELD-treated patients was 17.6 years (median 15 years), 62% were less than 18 years old (40% age 12 to 17; 21% age 8 to 11), 38% were 18 years and older (36% age 18 to 34; 2% age ≥35), and 64% were male. The population was 72% White, 26% Asian, 1% Black or African American, 1% were multiple or unknown race, and less than 1% American Indian or Alaska Native; 5% were Hispanic or Latino ethnicity. Common Adverse Reactions Cytokine Release Syndrome (CRS) In Study TN-10, CRS was reported in 2% of TZIELD-treated patients compared to 0% of placebo-treated patients. In the PROTECT Study, CRS was reported in 9% of TZIELD-treated patients compared to 1% of placebo-treated patients. Of the 39 TZIELD-treated patients developed CRS (5% of all TZIELD-treated patients), in the pool of 5 clinical trials, 13% of the CRS cases were serious adverse reactions [see Warnings and Precautions (5.2) ] . Liver transaminase elevations were observed in 56% of TZIELD-treated patients who experienced CRS; 64% were up to 2.5 times ULN, 32% were more than 2.5 to 5 times ULN, and 4.5% were greater than 5 –10 times ULN. Serious Infections In Study TN-10, serious infections (cellulitis, gastroenteritis, pneumonia, wound infection) were reported in 9% (4/44) of TZIELD-treated patients compared to 0% (0/32) of placebo-treated patients any time during or after the first dose of study treatment. In clinical trials, serious infections were reported in 3.5% of TZIELD-treated patients compared to 2% of control-treated patients any time during or after the first dose of study treatment. Rash and Hypersensitivity Reactions Hypersensitivity reactions were reported with TZIELD treatment in Study TN-10. Serum sickness was observed in 2% (1/44) of TZIELD-treated patients compared to 0% (0/32) of placebo-treated patients. The patient who developed serum sickness had a prior history of positive anti-nuclear antibody and presented with arthralgias and elevated c-reactive protein and low C4 complement five days after completing their course of TZIELD; illness resolved in 2.5 months. In the PROTECT Study, hypersensitivity reactions were reported in 1% of TZIELD-treated patients and 0% in the placebo group. One patient in the TZIELD group experienced delayed hypersensitivity. The patient had a prior history of allergic rhinitis and presented with symptoms of rash and arthralgia 16 days after completing Course 1. The event resolved with antihistamine treatment. In the pool of 5 clinical trials of patients with Stage 2 or Stage 3 T1D: Anaphylaxis (with hypoxia and bronchospasm) was observed in one TZIELD-treated patient who was hospitalized. Angioedema (periorbital and facial) was observed in 0.3% TZIELD-treated patients, compared to 0% in control-treated patients. Peripheral and generalized edema was reported in 1.6% of TZIELD-treated patients and 0% of control-treated patients. Rash was observed in 48% of TZIELD-treated patients compared to 15% in control-treated patients, with 33 excess cases of rash per 100 patients. The majority of events of rash observed with TZIELD treatment were not serious and resolved without intervention; although 0.3% (2/773) of TZIELD-treated patients had a serious rash compared to 0% (0/245) of placebo-treated patients. Urticaria was reported in 1.9% of TZIELD-treated patients and in 1.2% of control-treated patients. Immunogenicity: Anti-Drug Antibody-Associated Adverse Reactions In Study TN-10, rash occurred in 39% of TZIELD-treated patients who developed anti-teplizumab-mzwv antibodies and in 33% of TZIELD-treated patients who did not develop anti-teplizumab-mzwv antibodies [see Clinical Pharmacology (12.6) ]. In the PROTECT Study, rash occurred in 30% of TZIELD-treated patients who developed anti-teplizumab-mzwv antibodies and in 17% of TZIELD-treated patients who did not develop anti-teplizumab-mzwv antibodies [see Clinical Pharmacology (12.6) ]. Open Label Study in Pediatric Patients Age 1 to Less Than 8 Years with Stage 2 T1D The safety of TZIELD was evaluated in a non-randomized, single arm, open-label, multicenter study in 23 pediatric patients age 1 to less than 8 years with Stage 2 T1D ( PETITE-T1D Study; NCT05757713)[see Clinical Pharmacology (12.3) ]. In this trial, 87% completed the full 14-day treatment course. The median age was 4.9 years (1 patient was less than 2 years old; 52% were 2 to less than 5 years old; 44% were 5 to less than 8 years old; range 1.7 to 6.8 years) and 52% were female. The majority of the population (96%) was White and one patient (4%) was Asian; 3 patients (13%) were Hispanic or Latino ethnicity. At baseline, 87% of participants had a first-degree relative with T1D. The majority (87%) were positive for 3 or more diabetes-related autoantibodies. The most common autoantibodies were anti-insulin (87%), anti-ICA (85%), anti-GAD65 (83%), anti-ZnT8 (74%), and anti-IA2 (68%). The median HbA1c was 5.5%. Overall, the safety profile of TZIELD observed in pediatric patients less than 8 years of age with Stage 2 T1D was consistent with that observed in patients 8 years of age and older with Stage 2 T1D. The most common adverse reactions that occurred in patients less than 8 years of age were vomiting (52%) and diarrhea (30%). Other Adverse Reactions Lymphopenia In Study TN-10, lymphopenia was reported in 73% of TZIELD-treated patients compared to 6% of placebo-treated patients. The average lymphocyte count nadir occurred at Day 5 of treatment, with recovery and return to baseline by Week 6 [see Warnings and Precautions (5.4) ]. In the PROTECT Study, lymphopenia was reported in 51% of TZIELD-treated patients compared to 3% of placebo-treated patients. Lymphocyte count nadir occurred at approximately Day 4 of treatment, with recovery and return to baseline by Week 4 [see Warnings and Precautions (5.4) ]. Neutropenia In Study TN-10, neutropenia was observed in 7% of TZIELD-treated patients compared to 3% of placebo-treated patients. In the PROTECT Study, neutropenia was observed in 23% of TZIELD-treated patients compared to 5% of placebo-treated patients. Decreased Hemoglobin and Thrombocytopenia In the pool of 5 clinical trials, decreased hemoglobin was reported in 27% of TZIELD-treated patients compared to 21% of placebo-treated patients, and thrombocytopenia was reported in 13% of TZIELD-treated patients compared to 5% of placebo-treated patients during the 14-day treatment course; recovery occurred within 2 to 4 weeks of treatment. In these clinical trials, 1.8% of TZIELD-treated patients discontinued treatment due to hemoglobin less than 8.5 g/dL (or a decrease of more than 2 g/dL to a value less than 10 g/dL), and 1% discontinued TZIELD due to platelet count less than 50,000 platelets/mcL. Liver Enzyme Elevations Liver enzyme and bilirubin elevations were observed in TZIELD-treated patients, both in the context of CRS and in patients without CRS. In the pool of 5 clinical trials, ALT increased was reported in 25% of TZIELD-treated patients compared to 11% of placebo-treated patients during the 14-day treatment course. On laboratory analysis, 5.1% of TZIELD-treated patients experienced a peak ALT more than 3 times the ULN compared to 0.8% of control-treated patients. Most liver enzyme elevations were transient and resolved 1–2 weeks after treatment; 98% resolved by week 14. Procedure-Related Venous Thrombosis Venous thrombus and thrombophlebitis have been reported in patients receiving teplizumab intravenously administered via peripherally inserted central catheter (PICC). In the pool of 5 clinical trials of patients, deep vein thrombus was reported in 0.4% of TZIELD-treated patients compared to 0 placebo-treated patients. One teplizumab-treated patient (4.3%) in the PETITE-T1D study experienced a deep vein thrombosis. Other Laboratory Abnormalities In the pool of 5 clinical trials, other laboratory abnormalities including decreased bicarbonate (15% in TZIELD-treated patients, compared to 7% in placebo-treated patients) and decreased blood calcium (19% in TZIELD-treated patients, compared to 13% in placebo-treated patients) were noted.

<table width="85%"><caption>Table 2. Common Adverse Reactions<footnote>That occurred during treatment and through 28 days after the last study drug administration.</footnote> in Adult and Pediatric Patients Aged 8 Years and Older with Stage 2 T1D (Study TN-10)<footnote>Adverse reactions that occurred in 2 or more TZIELD-treated patients</footnote></caption><col width="40%" align="left" valign="middle"/><col width="30%" align="center" valign="middle"/><col width="30%" align="center" valign="middle"/><thead><tr><th styleCode="Lrule Rrule">Adverse Reaction</th><th styleCode="Rrule">TZIELD N=44</th><th styleCode="Rrule">Placebo N=32</th></tr></thead><tbody><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Lymphopenia<footnote ID="t2f3">Grouped term includes other related terms</footnote></td><td styleCode="Rrule">73%</td><td styleCode="Rrule">6%</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Rash<footnoteRef IDREF="t2f3"/></td><td styleCode="Rrule">36%</td><td styleCode="Rrule">0%</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Leukopenia<footnoteRef IDREF="t2f3"/></td><td styleCode="Rrule">21%</td><td styleCode="Rrule">0%</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Headache</td><td styleCode="Rrule">11%</td><td styleCode="Rrule">6%</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Neutropenia<footnoteRef IDREF="t2f3"/></td><td styleCode="Rrule">5%</td><td styleCode="Rrule">3%</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Increased alanine aminotransferase</td><td styleCode="Rrule">5%</td><td styleCode="Rrule">3%</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Nausea</td><td styleCode="Rrule">5%</td><td styleCode="Rrule">3%</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Diarrhea</td><td styleCode="Rrule">5%</td><td styleCode="Rrule">0%</td></tr><tr><td styleCode="Lrule Rrule">Nasopharyngitis</td><td styleCode="Rrule">5%</td><td styleCode="Rrule">0%</td></tr></tbody></table>

<table width="85%"><caption>Table 3. Common Adverse Reactions<footnote>Adverse reactions occurring in equal or more than 5% of participants in the TZIELD group, higher in TZIELD compared to placebo, in treatment course 1 through 28 days after the last dose.</footnote> in Pediatric Patients Aged 8 to 17 Years with Stage 3 T1D (PROTECT Study)</caption><col width="50%" align="left" valign="middle"/><col width="25%" align="center" valign="middle"/><col width="25%" align="center" valign="middle"/><thead><tr><th styleCode="Lrule Rrule">Adverse Reaction</th><th styleCode="Rrule">TZIELD n=217</th><th styleCode="Rrule">Placebo n=111</th></tr></thead><tbody><tr styleCode="Botrule"><td styleCode="Lrule Rrule" colspan="3"><content styleCode="bold">Course 1</content></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Lymphopenia<footnote ID="t3f2">Grouped term includes other related terms.</footnote></td><td styleCode="Rrule">51%</td><td styleCode="Rrule">3%</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Rash<footnoteRef IDREF="t3f2"/></td><td styleCode="Rrule">51%</td><td styleCode="Rrule">9%</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Leukopenia<footnoteRef IDREF="t3f2"/></td><td styleCode="Rrule">34%</td><td styleCode="Rrule">3%</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Nausea</td><td styleCode="Rrule">34%</td><td styleCode="Rrule">12%</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Headache</td><td styleCode="Rrule">29%</td><td styleCode="Rrule">16%</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Vomiting</td><td styleCode="Rrule">26%</td><td styleCode="Rrule">5%</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Neutropenia<footnoteRef IDREF="t3f2"/></td><td styleCode="Rrule">23%</td><td styleCode="Rrule">5%</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Abdominal pain<footnoteRef IDREF="t3f2"/></td><td styleCode="Rrule">18%</td><td styleCode="Rrule">11%</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Pyrexia</td><td styleCode="Rrule">16%</td><td styleCode="Rrule">3%</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Alanine aminotransferase increased</td><td styleCode="Rrule">11%</td><td styleCode="Rrule">0%</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Diarrhea</td><td styleCode="Rrule">10%</td><td styleCode="Rrule">6%</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Cytokine release syndrome</td><td styleCode="Rrule">7%</td><td styleCode="Rrule">1%</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Hypotension</td><td styleCode="Rrule">7%</td><td styleCode="Rrule">6%</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Aspartate aminotransferase increased</td><td styleCode="Rrule">7%</td><td styleCode="Rrule">1%</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Hemoglobin decreased<footnoteRef IDREF="t3f2"/></td><td styleCode="Rrule">5%</td><td styleCode="Rrule">4%</td></tr><tr><td styleCode="Lrule Rrule"> Chills</td><td styleCode="Rrule">5%</td><td styleCode="Rrule">0%</td></tr></tbody></table>