DATROWAY by is a Prescription medication manufactured, distributed, or labeled by Daiichi Sankyo Inc.. Drug facts, warnings, and ingredients follow.
DATROWAY is a Trop-2-directed antibody and topoisomerase inhibitor conjugate indicated for the treatment of adult patients with unresectable or metastatic, hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative (IHC 0, IHC 1+ or IHC 2+/ISH-) breast cancer who have received prior endocrine-based therapy and chemotherapy for unresectable or metastatic disease. (1)
For injection: 100 mg lyophilized powder in a single-dose vial. (3)
None. (4)
The most common adverse reactions (≥20%), including laboratory abnormalities, were stomatitis, nausea, fatigue, decreased leukocytes, decreased calcium, alopecia, decreased lymphocytes, decreased hemoglobin, constipation, decreased neutrophils, dry eye, vomiting, increased ALT, keratitis, increased AST, and increased alkaline phosphatase. (6.1)
To report SUSPECTED ADVERSE REACTIONS, contact Daiichi Sankyo, Inc. at 1-877-437-7763 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
See 17 for PATIENT COUNSELING INFORMATION and Medication Guide.
Revised: 1/2025
DATROWAY is indicated for the treatment of adult patients with unresectable or metastatic, hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative (IHC 0, IHC 1+ or IHC 2+/ISH-) breast cancer who have received prior endocrine-based therapy and chemotherapy for unresectable or metastatic disease.
The recommended dosage of DATROWAY is 6 mg/kg (up to a maximum of 540 mg for patients ≥90 kg) administered as an intravenous infusion once every 3 weeks (21-day cycle) until disease progression or unacceptable toxicity.
If a planned dose is delayed or missed, administer as soon as possible; do not wait until the next planned cycle. Adjust the schedule of administration to maintain a 3-week interval between doses.
Administer DATROWAY in a setting where cardiopulmonary resuscitation medication and equipment are available.
Conduct an ophthalmic exam including visual acuity testing, slit lamp examination (with fluorescein staining), intraocular pressure, and fundoscopy at initiation of DATROWAY, annually while on treatment, at end of treatment, and as clinically indicated.
Administer DATROWAY with the premedication and concomitant medications described in Table 1.
Monitor patients for infusion-related reactions for at least 1 hour for the first 2 cycles of DATROWAY infusions. If there are no infusion-related reactions observed, monitor patients for at least 30 minutes for all subsequent cycles of infusions.
Premedication * | Examples (or equivalent) | Timing of Treatment/Duration |
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Eye drops
[see Warnings and Precautions (5.2)] | Preservative-free lubricant eye drops | Administer at least four times daily and as needed |
Mouthwash
[see Warnings and Precautions (5.3)] | Steroid-containing mouthwash (dexamethasone oral solution 0.1 mg/mL) | Administer four times daily and as needed |
Antihistamine
[see Adverse Reactions (6.1)] | Diphenhydramine (25 to 50 mg) administered intravenously or orally | Administer 30-60 minutes prior to each infusion |
Antipyretic
[see Adverse Reactions (6.1)] | Acetaminophen (650 to 1,000 mg) administered intravenously or orally | Administer 30-60 minutes prior to each infusion |
Antiemetics
[see Adverse Reactions (6.1)] | 5-HT3 serotonin receptor antagonist or appropriate alternatives intravenously or oral | Prior to each infusion and thereafter as needed |
Dosage Modifications for Adverse Reactions
The recommended dose reduction levels for adverse reactions are described in Table 2.
Dose Reductions | Recommended Dose |
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First | 4 mg/kg (up to a maximum of 360 mg for patients ≥90 kg) |
Second | 3 mg/kg (up to a maximum of 270 mg for patients ≥90 kg) |
Third | Permanently discontinue |
Do not re-escalate the DATROWAY dose after a dose reduction. Permanently discontinue DATROWAY in patients who are unable to tolerate 3 mg/kg intravenously once every 3 weeks.
The recommended dosage modifications for adverse reactions of DATROWAY are described in Table 3.
Adverse Reaction | Severity * | Dosage Modifications |
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Interstitial Lung Disease (ILD)/Pneumonitis
[see Warnings and Precautions (5.1)] | Asymptomatic ILD/pneumonitis Grade 1 | Withhold DATROWAY until ILD/pneumonitis is completely resolved, then:
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Symptomatic ILD/pneumonitis Grade 2 or greater |
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Keratitis
[see Warnings and Precautions (5.2) and Adverse Reactions (6.1)] | Nonconfluent superficial keratitis |
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Confluent superficial keratitis, a cornea epithelial defect, or 3-line or more loss in best corrected visual acuity |
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Corneal ulcer or stromal opacity or best corrected distance visual acuity 20/200 or worse |
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Corneal perforation |
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Stomatitis
[see Warnings and Precautions (5.3)] | Grade 1 |
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Grade 2 |
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Grade 3 |
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Grade 4 |
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Infusion-Related Reactions (IRR)
[see Adverse Reactions (6.1)] | Grade 1 |
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Grade 2 |
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Grade 3 or 4 |
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Other Non-Hematologic Adverse Reactions
[see Adverse Reactions (6.1)] | Grade 3 |
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Grade 4 |
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Reconstitute and further dilute DATROWAY prior to intravenous infusion. Use appropriate aseptic technique.
DATROWAY (datopotamab deruxtecan-dlnk) is a hazardous drug. Follow applicable special handling and disposal procedures.1
Reconstitution
Dilution
Administration
DATROWAY can cause severe, life-threatening, or fatal interstitial lung disease (ILD) or pneumonitis.
In TROPION-Breast01, ILD/pneumonitis occurred in 4.2% of patients treated with DATROWAY, including 0.5% of patients with Grade 3-4 ILD/pneumonitis, and 0.3% with fatal ILD/pneumonitis. Six patients (1.7%) permanently discontinued DATROWAY due to ILD/pneumonitis. The median time-to-onset of ILD/pneumonitis was 3.5 months (range: 1.2 months to 10.8 months). Patients were excluded from TROPION-Breast01 for a history of ILD/pneumonitis requiring treatment with steroids or for ongoing ILD/pneumonitis.
Monitor patients for new or worsening respiratory symptoms indicative of ILD/pneumonitis (e.g., dyspnea, cough, fever) during treatment with DATROWAY. For asymptomatic (Grade 1) ILD/pneumonitis, consider corticosteroid treatment (e.g., ≥0.5 mg/kg/day prednisolone or equivalent). For symptomatic ILD/pneumonitis (Grade 2 or greater), promptly initiate systemic corticosteroid treatment (e.g., ≥1 mg/kg/day prednisolone or equivalent) and continue for at least 14 days followed by gradual taper for at least 4 weeks.
Withhold DATROWAY in patients with suspected ILD/pneumonitis and permanently discontinue DATROWAY if ≥Grade 2 ILD/pneumonitis is confirmed [see Dosage and Administration (2.3)].
DATROWAY can cause ocular adverse reactions including dry eye, keratitis, blepharitis, meibomian gland dysfunction, increased lacrimation, conjunctivitis, and blurred vision.
In TROPION-Breast01, ocular adverse reactions occurred in 51% of patients treated with DATROWAY. Seven patients (1.9%) experienced Grade 3 ocular adverse reactions, including dry eye, keratitis, and blurred vision. The most common (≥5%) ocular adverse reactions were dry eye (27%), keratitis (24%), blepharitis and increased lacrimation (8% each), and meibomian gland dysfunction (7%). Patients with clinically significant corneal disease were excluded from TROPION-Breast01.
The median time to onset for ocular adverse reactions was 2.1 months (range: 0.03 months to 23.2 months). Of the patients who experienced ocular adverse reactions, 45% had complete resolution; 9% had partial improvement (defined as a decrease in severity by one or more grades from the worst grade at last follow up). Ocular adverse reactions led to permanent discontinuation of DATROWAY in 0.8% of patients.
Advise patients to use preservative-free lubricant eye drops several times daily for prophylaxis. Advise patients to avoid use of contact lenses unless directed by an eye care professional.
Refer patients to an eye care professional for an ophthalmic exam including visual acuity testing, slit lamp examination (with fluorescein staining), intraocular pressure, and fundoscopy at treatment initiation, annually while on treatment, at end of treatment, and as clinically indicated.
Promptly refer patients to an eye care professional for any new or worsening ocular adverse reactions. Monitor patients for ocular adverse reactions during treatment with DATROWAY, and if diagnosis is confirmed, dose delay, dose reduce, or permanently discontinue DATROWAY based on severity [see Dosage and Administration (2.3)].
DATROWAY can cause stomatitis, including mouth ulcers and oral mucositis.
In the TROPION-Breast01 study, stomatitis occurred in 59% of patients treated with DATROWAY, including 7% of patients with Grade 3-4 events. Median time to first onset was 0.7 months (range: 0.03 months to 8.8 months). Stomatitis led to interruption of DATROWAY in 1.9%, dosage reductions in 13%, and permanent discontinuation in 0.3% of patients.
In patients who received DATROWAY, 38% used a mouthwash containing corticosteroid for management or prophylaxis of stomatitis/oral mucositis at any time during the treatment.
Advise patients to use a steroid-containing mouthwash for prophylaxis and treatment of stomatitis. Instruct the patient to hold ice chips or ice water in the mouth throughout the infusion of DATROWAY.
Monitor patients for signs and symptoms of stomatitis. If stomatitis occurs, increase the frequency of mouthwash and administer other topical treatments as clinically indicated. Based on the severity of the adverse reaction, withhold, dose reduce, or permanently discontinue DATROWAY [see Dosage and Administration (2.3)].
Based on its mechanism of action, DATROWAY can cause embryo-fetal harm when administered to a pregnant woman because the topoisomerase inhibitor component of DATROWAY, DXd [see Description (11)], is genotoxic and affects actively dividing cells [see Use in Specific Populations (8.1), Clinical Pharmacology (12.1), Nonclinical Toxicology (13.1)].
Advise patients of the potential risk to a fetus. Advise female patients of reproductive potential to use effective contraception during treatment with DATROWAY and for 7 months after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with DATROWAY and for 4 months after the last dose [see Use in Specific Populations (8.1, 8.3)].
The following clinically significant adverse reactions are described elsewhere in the labeling:
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.
Unresectable or Metastatic, HR-Positive, HER2-Negative Breast Cancer
TROPION-Breast01
The safety of DATROWAY was evaluated in 360 patients with unresectable or metastatic HR-positive, HER2-negative (IHC 0, IHC1+ or IHC2+/ISH-) breast cancer who received at least one dose of DATROWAY 6 mg/kg in TROPION-Breast01 [see Clinical Studies (14.1)]. DATROWAY was administered by intravenous infusion once every three weeks. The median duration of treatment was 6.7 months (range: 0.7 months to 16.1 months) for patients who received DATROWAY.
Serious adverse reactions occurred in 15% of patients who received DATROWAY. Serious adverse reactions in >0.5% of patients who received DATROWAY were urinary tract infection (1.9%), COVID-19 infection (1.7%), ILD/pneumonitis (1.1%), acute kidney injury, pulmonary embolism, vomiting, diarrhea, hemiparesis, and anemia (0.6% each). Fatal adverse reactions occurred in 0.3% of patients who received DATROWAY and were due to ILD/pneumonitis.
Permanent discontinuation of DATROWAY due to an adverse reaction occurred in 3.1% of patients. Adverse reactions which resulted in permanent discontinuation of DATROWAY in >0.5% of patients included ILD/pneumonitis (1.7%) and fatigue (0.6%).
Dosage interruptions of DATROWAY due to an adverse reaction occurred in 22% of patients. Adverse reactions which required dosage interruption in >1% of patients included COVID-19 (3.3%), infusion-related reaction (1.4%), ILD/pneumonitis (1.9%), stomatitis (1.9%), fatigue (1.7%), keratitis (1.4%), acute kidney injury (1.1%), and pneumonia (1.1%).
Dose reductions of DATROWAY due to an adverse reaction occurred in 23% of patients. Adverse reactions which required dose reduction in >1% of patients included stomatitis (13%), fatigue (3.1%), nausea (2.5%), and weight decrease (1.9%).
The most common (≥20%) adverse reactions, including laboratory abnormalities, were stomatitis, nausea, fatigue, decreased leukocytes, decreased calcium, alopecia, decreased lymphocytes, decreased hemoglobin, constipation, decreased neutrophils, dry eye, vomiting, increased ALT, keratitis, increased AST, and increased alkaline phosphatase.
Adverse Reactions | DATROWAY N=360 | Chemotherapy N=351 |
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All Grades % | Grades 3 or 4 % | All Grades % | Grades 3 or 4 % |
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Events were graded using NCI CTCAE v5.0. | ||||
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Gastrointestinal Disorders | ||||
Stomatitis * | 59 | 7 | 17 | 2.6 |
Nausea | 56 | 1.4 | 27 | 0.6 |
Constipation | 34 | 0.3 | 17 | 0 |
Vomiting | 24 | 1.1 | 12 | 1.1 |
Diarrhea | 11 | 0.6 | 19 | 1.4 |
Abdominal pain * | 11 | 0.6 | 15 | 1.4 |
General Disorders and Administration Site Conditions | ||||
Fatigue † | 44 | 4.2 | 40 | 3.7 |
Skin and Subcutaneous Tissue Disorders | ||||
Alopecia | 38 | 0 | 22 | 0 |
Rash * | 19 | 0 | 17 | 2.3 |
Eye Disorders | ||||
Dry eye | 27 | 0.8 | 13 | 0 |
Keratitis ‡ | 24 | 1.1 | 10 | 0 |
Metabolism and Nutrition Disorders | ||||
Decreased appetite | 16 | 1.4 | 16 | 0.9 |
Infections and Infestations | ||||
COVID-19 * | 16 | 1.4 | 13 | 0.9 |
Respiratory, Thoracic, and Mediastinal Disorders | ||||
Cough * | 15 | 0 | 10 | 0 |
Clinically relevant adverse reactions occurring in <10% of patients who received DATROWAY included infusion-related reactions (including bronchospasm), ILD/pneumonitis, headache, pruritus, dry skin, dry mouth, conjunctivitis, blepharitis, meibomian gland dysfunction, blurred vision, increased lacrimation, photophobia, visual impairment, skin hyperpigmentation, and madarosis.
Laboratory Abnormality | DATROWAY * | Chemotherapy * | ||
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All Grades % | Grades 3-4 % | All Grades % | Grades 3-4 % |
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Frequencies were based on NCI CTCAE v5.0 grade-derived laboratory abnormalities. | ||||
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Hematology | ||||
Decreased leukocytes | 41 | 1.1 | 63 | 18 |
Decreased lymphocytes | 36 | 9 | 42 | 11 |
Decreased hemoglobin | 35 | 2.8 | 51 | 4.4 |
Decreased neutrophils | 30 | 1.6 | 61 | 35 |
Chemistry | ||||
Decreased calcium | 39 | 1.4 | 43 | 1.2 |
Increased AST | 23 | 1.9 | 28 | 0.9 |
Increased ALT | 24 | 1.7 | 31 | 0.6 |
Increased alkaline phosphatase | 23 | 0.6 | 20 | 0.6 |
Risk Summary
Based on its mechanism of action, DATROWAY can cause embryo-fetal harm when administered to a pregnant woman because the topoisomerase inhibitor component of DATROWAY, DXd, is genotoxic and affects actively dividing cells [see Clinical Pharmacology (12.1), Nonclinical Toxicology (13.1)]. There are no available data on the use of DATROWAY in pregnant women to inform a drug-associated risk. Advise patients of the potential risks to a 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.
Risk Summary
There are no data regarding the presence of datopotamab deruxtecan-dlnk or its metabolites in human milk, the effects on the breastfed child, or the effects on milk production. Because of the potential for serious adverse reactions in a breastfed child, advise women not to breastfeed during treatment with DATROWAY and for 1 month after the last dose.
DATROWAY can cause embryo-fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1)].
Pregnancy Testing
Verify pregnancy status of females of reproductive potential prior to initiation of DATROWAY.
Contraception
Females
Advise females of reproductive potential to use effective contraception during treatment with DATROWAY and for 7 months after the last dose.
Males
Because of the potential for genotoxicity, advise male patients with female partners of reproductive potential to use effective contraception during treatment with DATROWAY and for 4 months after the last dose [see Nonclinical Toxicology (13.1)].
Infertility
Based on findings in animal toxicity studies, DATROWAY may impair male and female reproductive function and fertility. The effects on reproductive organs in animals were irreversible [see Nonclinical Toxicology (13.1)].
Safety and effectiveness of DATROWAY have not been established in pediatric patients.
Of the 365 patients in TROPION-Breast01 treated with DATROWAY 6 mg/kg, 25% were ≥65 years of age and 5% were ≥75 years of age. Grade ≥3 and serious adverse reactions were more common in patients ≥65 years (42% and 25%, respectively) compared to patients <65 years (33% and 15%, respectively). In TROPION-Breast01, no other meaningful differences in safety or efficacy were observed between patients ≥65 years of age versus younger patients.
A higher incidence of ILD/pneumonitis has been observed in patients with mild and moderate renal impairment (creatinine clearance [CLcr] 30 to <90 mL/min) [see Warnings and Precautions (5.1)]. Monitor patients with renal impairment for increased adverse reactions, including respiratory reactions. No dosage adjustment is recommended in patients with mild to moderate renal impairment [see Clinical Pharmacology (12.3)]. The effect of severe renal impairment (CLcr <30 mL/min) on the pharmacokinetics of datopotamab deruxtecan-dlnk or DXd is unknown.
No dosage adjustment is recommended in patients with mild hepatic impairment (total bilirubin ≤ULN and any AST >ULN or total bilirubin >1 to 1.5 times ULN and any AST). Limited data are available in patients with moderate hepatic impairment (total bilirubin >1.5 to 3 times ULN and any AST). Monitor patients with moderate hepatic impairment for increased adverse reactions [see Dosage and Administration (2.3)]. The recommended dosage of DATROWAY has not been established for patients with severe hepatic impairment (total bilirubin >3 times ULN and any AST) [see Clinical Pharmacology (12.3)].
Datopotamab deruxtecan-dlnk is a Trop2-directed antibody and topoisomerase inhibitor conjugate. Datopotamab deruxtecan-dlnk is an antibody-drug conjugate (ADC) composed of three components: 1) a humanized anti-Trop2 IgG1 monoclonal antibody (mAb), covalently linked to 2) a topoisomerase I inhibitor, via 3) a tetrapeptide-based cleavable linker. Deruxtecan is composed of a protease-cleavable maleimide tetrapeptide linker and the topoisomerase inhibitor, DXd, which is an exatecan derivative.
The antibody is produced in Chinese hamster ovary cells by recombinant DNA technology, and the topoisomerase inhibitor and linker are produced by chemical synthesis. Approximately 4 molecules of deruxtecan are attached to each antibody molecule. Datopotamab deruxtecan-dlnk has the following structure:
DATROWAY (datopotamab deruxtecan-dlnk) for injection is a sterile, white to yellowish white, preservative-free lyophilized powder in single-dose vials. Each vial delivers 100 mg of datopotamab deruxtecan-dlnk, L-histidine (3.88 mg), L-histidine hydrochloride monohydrate (5.25 mg), polysorbate 80 (1.50 mg), and sucrose (450 mg). Following reconstitution with 5 mL of Sterile Water for Injection, USP, the resulting concentration of datopotamab deruxtecan-dlnk is 20 mg/mL with a pH of 6.0. The resulting solution is administered by intravenous infusion following dilution.
Datopotamab deruxtecan-dlnk, is a Trop-2-directed antibody-drug conjugate. The antibody is a humanized anti-Trop2 IgG1. The small molecule, DXd, is a topoisomerase I inhibitor attached to the antibody by a cleavable linker. Following binding to Trop2 on cells, including tumor cells, datopotamab deruxtecan-dlnk undergoes internalization and intracellular linker cleavage by lysosomal enzymes. Upon release, the membrane-permeable DXd causes DNA damage and apoptotic cell death. Datopotamab deruxtecan-dlnk had anti-tumor activity in a mouse model of breast cancer.
Datopotamab deruxtecan-dlnk time course of pharmacodynamic response is unknown.
Exposure-Response Relationships
A relationship between datopotamab deruxtecan-dlnk exposure and efficacy has not been fully characterized in breast cancer.
Higher datopotamab deruxtecan-dlnk systemic exposure is associated with a higher incidence rate of serious adverse reactions, dosage interruptions, dose reductions, stomatitis/oral mucositis, ocular adverse reactions, and Grade ≥3 adverse reactions.
Datopotamab deruxtecan-dlnk and DXd exposure after the first dose of the approved recommended dosage of cycle 1 are provided in Table 6. Datopotamab deruxtecan-dlnk and released DXd maximum concentration (Cmax) and area under the time-concentration curve (AUC) increases proportionally over a dose range of 4 mg/kg to 10 mg/kg (approximately 0.7 to 1.7 times the approved recommended dosage). No clinically significant datopotamab deruxtecan-dlnk accumulation occurs between cycles 1 and 3.
PK Parameter | Datopotamab deruxtecan-dlnk | DXd |
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Abbreviations: Cmax =maximum concentration; AUC =area under the time-concentration curve | ||
Cmax | 154 µg/mL (20%) | 2.8 ng/mL (58%) |
AUC | 671 µg*day/mL (31%) | 18 ng*day/mL (43%) |
Distribution
Datopotamab deruxtecan-dlnk mean steady state volume of distribution is 3.5 (23%) L.
DXd plasma protein binding is approximately 98% and the blood-to-plasma concentration ratio is 0.6 in vitro.
Elimination
The datopotamab deruxtecan-dlnk median elimination half-life (t1/2) is 4.8 days (1.0, 8.2) and the released DXd median apparent t1/2 is approximately 5.5 days (3.2, 8.8). The estimated datopotamab deruxtecan-dlnk clearance is 0.6 (31.5%) L/day.
Metabolism
Datopotamab deruxtecan-dlnk undergoes intracellular cleavage by lysosomal enzymes to release DXd.
The humanized Trop-2 IgG1 monoclonal antibody is expected to be degraded into small peptides and amino acids via catabolic pathways in the same manner as endogenous IgG.
In vitro, DXd is primarily metabolized by CYP3A4.
Specific Populations
The mean volume of distribution and clearance of datopotamab deruxtecan-dlnk and DXd increase with increasing body weight (36 kg to 156 kg).
No clinically significant differences in the pharmacokinetics of datopotamab deruxtecan-dlnk or DXd were observed based on age (26 to 86 years), race (Asian, White, or Black), sex, mild hepatic impairment (total bilirubin ≤ULN and any AST >ULN or total bilirubin >1 to 1.5 times ULN and any AST), or mild to moderate renal impairment (CLcr 30 to <90 mL/min).
The pharmacokinetics of datopotamab deruxtecan-dlnk in patients with moderate hepatic impairment (total bilirubin >1.5 to 3 times ULN and any AST) was comparable to patients with normal hepatic function (total bilirubin and AST ≤ULN). The steady state average DXd AUC was 2.4-fold higher in patients with moderate hepatic impairment compared to patients with normal hepatic function. The effect of severe hepatic impairment (total bilirubin >3 times ULN and any AST) or severe renal impairment (CLcr <30 mL/min) on datopotamab deruxtecan-dlnk or DXd pharmacokinetics is unknown.
Drug Interaction Studies
Clinical Studies and Model-Informed Approaches
No clinically significant differences in DXd pharmacokinetics were predicted when used concomitantly with itraconazole (strong CYP3A inhibitor) or ritonavir (dual OATP1B and CYP3A inhibitor).
Carcinogenicity studies have not been conducted with datopotamab deruxtecan-dlnk.
The topoisomerase inhibitor component of datopotamab deruxtecan-dlnk, DXd, was clastogenic in both an in vivo rat bone marrow micronucleus assay and an in vitro Chinese hamster lung chromosome aberration assay and was not mutagenic in an in vitro bacterial reverse mutation assay.
Dedicated fertility studies have not been conducted with datopotamab deruxtecan-dlnk. In a 3-month repeat-dose toxicity study, intravenous administration of datopotamab deruxtecan-dlnk once every 3 weeks in rats resulted in decreased weights in the testes and epididymides, degeneration of the germinal epithelium and atrophy of seminiferous tubules in testes, and cell debris, decreased number of sperm, and single-cell necrosis of the ductal epithelium in epididymides at 200 mg/kg (approximately 29 times the human recommended dose of 6 mg/kg based on AUC). Findings in female rats included increased atretic follicles in the ovary and single cell necrosis of mucosal epithelium in the vagina at 200 mg/kg. These findings, except for the lesions in the testis and epididymis, were not observed after a 2-month recovery period.
TROPION-Breast01
The efficacy of DATROWAY was evaluated in TROPION-Breast01 (NCT05104866), a multicenter, open-label, randomized trial of 732 patients with unresectable or metastatic HR-positive, HER2-negative (IHC 0, IHC1+ or IHC2+/ISH-) breast cancer. Eligible patients must have progressed on and deemed not suitable for further endocrine therapy. Patients were required to have received 1 or 2 lines of prior chemotherapy in the unresectable or metastatic disease setting. Patients were excluded for a history of ILD/pneumonitis requiring treatment with steroids, ongoing ILD/pneumonitis, clinically active brain metastases, or clinically significant corneal disease at screening. Patients were also excluded for ECOG performance status >1. Randomization was stratified by previous lines of chemotherapy (one or two), prior treatment with a CDK4/6 inhibitor (yes or no), and geographical region.
A total of 732 patients were randomized 1:1 to receive either DATROWAY 6 mg/kg (N=365) by intravenous infusion every 3 weeks or investigator's choice of chemotherapy (N=367) until unacceptable toxicity or disease progression. Single agent chemotherapy was determined by the investigator before randomization from one of the following choices: eribulin (60%), capecitabine (21%), vinorelbine (10%), or gemcitabine (9%).
The major efficacy outcomes were progression-free survival (PFS) as assessed by blinded independent central review (BICR) based on Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1 and overall survival (OS). Additional efficacy outcomes included confirmed objective response rate (ORR) and duration of response (DOR) by BICR.
The median age was 55 years (range 28-86); 22% were ≥65 years; 99% were female; 48% were White, 41% were Asian, 1.5% were Black or African American, and 11% were of Hispanic/Latino ethnicity; 57% had ECOG PS of 0 and 42% had ECOG PS of 1; 97% had visceral disease, 72% had liver metastases, and 8% had stable brain metastases.
Sixty percent (60%) of patients received prior endocrine therapy in the (neo)adjuvant setting, and 89% received prior endocrine therapy in the unresectable or metastatic setting. Eighty-three percent (83%) of patients had prior treatment with a CDK4/6 inhibitor. All patients received prior chemotherapy regimens in the unresectable or metastatic setting (81% received prior taxanes; 64% received prior anthracyclines). Sixty-two percent (62%) of patients had 1 prior chemotherapy regimen and 38% of patients had 2 prior chemotherapy regimens for treatment of unresectable or metastatic disease.
The study demonstrated a statistically significant improvement in PFS in patients randomized to DATROWAY compared to chemotherapy.
Efficacy results are shown in Table 7 and Figure 1.
DATROWAY (n=365) | Chemotherapy (n=367) |
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CI: Confidence interval; NS: not statistically significant | ||
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Progression-Free Survival * | ||
Number of events (%) | 212 (58) | 235 (64) |
Progressive Disease | 201 (55) | 218 (59) |
Death | 11 (3) | 17 (5) |
Median, months (95% CI) | 6.9 (5.7, 7.4) | 4.9 (4.2, 5.5) |
Hazard ratio (95% CI) † | 0.63 (0.52, 0.76) | |
p-value ‡, § | < 0.0001 | |
Overall Survival | ||
Number of events (%) | 223 (61) | 213 (58) |
Median, months (95% CI) | 18.6 (17.3, 20.1) | 18.3 (17.3, 20.5) |
Hazard ratio (95% CI) † | 1.01 (0.83, 1.22) | |
p-value ‡ | NS | |
Confirmed Objective Response Rate * | ||
n (%) | 133 (36) | 84 (23) |
(95% CI) | 31, 42 | 19, 28 |
Complete Response n (%) | 2 (0.5) | 0 |
Partial Response n (%) | 131 (36) | 84 (23) |
Duration of Response * | ||
Median, months (95% CI) | 6.7 (5.6, 9.8) | 5.7 (4.9, 6.8) |
Figure 1: Kaplan-Meier Plot of PFS by BICR in TROPION-Breast-01 |
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How Supplied
DATROWAY (datopotamab deruxtecan-dlnk) for injection is a white to yellowish white lyophilized powder supplied as:
Carton Contents | NDC |
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One 100 mg single-dose vial | NDC: 65597-801-01 |
Storage and Handling
Store vials in a refrigerator at 2ºC to 8ºC (36ºF to 46ºF) in the original carton to protect from light until time of reconstitution. Do not freeze. Do not shake the reconstituted or diluted solution [see Dosage and Administration (2.4)].
DATROWAY (datopotamab deruxtecan-dlnk) is a hazardous drug. Follow applicable special handling and disposal procedures.1
Advise the patient to read the FDA-approved patient labeling (Medication Guide).
Interstitial Lung Disease/Pneumonitis
Ocular Adverse Reactions
Stomatitis
Embryo-Fetal Toxicity
Lactation
Infertility
Manufactured by:
Daiichi Sankyo, Inc., Basking Ridge, NJ 07920
U.S. License No. 2128
Marketed by:
Daiichi Sankyo, Inc., Basking Ridge, NJ 07920 and AstraZeneca Pharmaceuticals LP, Wilmington, DE 19850
DATROWAY® is a registered trademark of Daiichi Sankyo Company, Ltd.
© 2025 Daiichi Sankyo Co., Ltd.
USPI-DAT-C6-0125-r001
This Medication Guide has been approved by the U.S. Food and Drug Administration. | Issued: 01/2025 | |
MEDICATION GUIDE
DATROWAY® (DAT-roe-way) (datopotamab deruxtecan-dlnk) for injection, for intravenous use |
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What is the most important information I should know about DATROWAY? DATROWAY can cause serious side effects, including:
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What is DATROWAY?
DATROWAY is a prescription medicine used to treat adults who have hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative breast cancer:
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Before receiving DATROWAY, tell your healthcare provider about all of your medical conditions, including if you:
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How will I receive DATROWAY?
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What are the possible side effects of DATROWAY? DATROWAY can cause serious side effects, including: The most common side effects of DATROWAY include: |
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DATROWAY may cause fertility problems in males and females, which may affect your ability to have children. Talk to your healthcare provider if you have concerns about fertility. These are not all of the possible side effects of DATROWAY. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. |
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General information about the safe and effective use of DATROWAY.
Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. You can ask your pharmacist or healthcare provider for information about DATROWAY that is written for health professionals. |
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What are the ingredients in DATROWAY?
Active ingredient: datopotamab deruxtecan-dlnk Inactive ingredients: L-histidine, L-histidine hydrochloride monohydrate, polysorbate 80, and sucrose Manufactured by: Daiichi Sankyo, Inc., Basking Ridge, NJ 07920 U.S. License No. 2128 Marketed by: Daiichi Sankyo, Inc., Basking Ridge, NJ 07920 and AstraZeneca Pharmaceuticals LP, Wilmington, DE 19850 DATROWAY® is a registered trademark of Daiichi Sankyo Company, Ltd. © 2025 Daiichi Sankyo Co., Ltd. USMG-DAT-C6-0125-r001 For more information, call 1-877-437-7763 or go to https://www.DATROWAY.com. |
NDC: 65597-801-01
Rx only
DATROWAY®
(datopotamab deruxtecan-dlnk)
For Injection
100 mg per vial
For Intravenous Infusion Only
Reconstitute and dilute prior to administration.
Single-dose vial. Discard unused portion.
Dispense the enclosed Medication Guide to
each patient.
Hazardous Drug
KEEP REFRIGERATED
1 vial
Daiichi-Sankyo
AstraZeneca
DATROWAY
datopotamab deruxtecan injection, powder, lyophilized, for solution |
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Labeler - Daiichi Sankyo Inc. (068605067) |
Mark Image Registration | Serial | Company Trademark Application Date |
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![]() DATROWAY 79366371 not registered Live/Pending |
DAIICHI SANKYO COMPANY, LIMITED 2023-01-25 |
![]() DATROWAY 79339642 not registered Live/Pending |
DAIICHI SANKYO COMPANY, LIMITED 2022-03-04 |