Datopotamab Deruxtecan-dlnk (Monograph)

Brand name: Datroway
Drug class: Antineoplastic Agents

Medically reviewed by Drugs.com on Aug 10, 2025. Written by ASHP.

Introduction

Datopotamab deruxtecan-dlnk, a Trop-2-directed antibody and topoisomerase inhibitor conjugate, is an antineoplastic agent.

Uses for Datopotamab Deruxtecan-dlnk

Datopotamab deruxtecan-dlnk has the following uses:

Datopotamab deruxtecan-dlnk is indicated for the treatment of adult patients with locally advanced or metastatic epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) who have received prior EGFR-directed therapy and platinum-based chemotherapy. This indication is approved under accelerated approval based on objective response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trial.

Datopotamab deruxtecan-dlnk is also 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.

Datopotamab Deruxtecan-dlnk Dosage and Administration

General

Datopotamab deruxtecan-dlnk is available in the following dosage form(s) and strength(s):

For injection: 100 mg lyophilized powder in a single-dose vial for reconstitution and dilution.

Dosage

It is essential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:

Adults

Dosage and Administration

For IV infusion only. Do not administer as an IV push or bolus.
Administer in a setting where cardiopulmonary resuscitation medication and equipment are available.
Reconstitute and further dilute the commercially available lyophilized drug prior to IV infusion. Reconstitute datopotamab deruxtecan-dlnk with sterile water for injection. Dilute reconstituted drug with 5% dextrose injection. DO NOT use sodium chloride injection.
Premedicate to reduce the risk of infusion reactions and nausea and vomiting.
Datopotamab deruxtecan-dlnk is a hazardous drug. Follow applicable special handling and disposal procedures.
The recommended dosage of datopotamab deruxtecan-dlnk is 6 mg/kg (up to a maximum of 540 mg for patients ≥90 kg) given as an IV infusion once every 3 weeks (21-day cycle) until disease progression or unacceptable toxicity.
Administer first infusion over 90 minutes. Observe patients during the infusion and for at least 1 hour following the initial dose for signs or symptoms of infusion-related reactions. If first infusion was tolerated, administer second infusion over 30 minutes. Observe patients during the infusion and for at least 1 hour after infusion. Administer subsequent infusions over 30 minutes if prior infusions were tolerated. Observe patients during the infusion and for at least 30 minutes after infusion.
See Full Prescribing Information for additional details on preparation and administration, and for dosage modification recommendations for adverse reactions.

Cautions for Datopotamab Deruxtecan-dlnk

Contraindications

None.

Warnings/Precautions

Interstitial Lung Disease/Pneumonitis

Datopotamab deruxtecan-dlnk can cause severe, life-threatening, or fatal interstitial lung disease (ILD) or pneumonitis.

Locally Advanced or Metastatic NSCLC

In the pooled safety population of 484 patients with NSCLC from TROPION-Lung01, TROPION-Lung05, and TROPION-PanTumor01, ILD/pneumonitis occurred in 7% of patients treated with datopotamab deruxtecan-dlnk, including 0.6% of patients with Grade 3 and 0.4% with Grade 4. There were 8 (1.7%) fatal cases. The median time to onset for ILD was 1.4 months (range: 0.2 months to 9 months). Eleven patients (2.3%) had datopotamab deruxtecan-dlnk withheld and 20 patients (4.1%) permanently discontinued therapy due to ILD/pneumonitis. Systemic corticosteroids were required in 79% (26/33) of patients with ILD/pneumonitis. ILD/pneumonitis resolved in 45% of patients.

Unresectable or Metastatic Breast Cancer

In the pooled safety population of 443 patients with breast cancer from TROPION-Breast01 and TROPION-PanTumor01, ILD/pneumonitis occurred in 3.6% of patients treated with datopotamab deruxtecan-dlnk, including 0.7% of patients with Grade 3. There was one fatal case (0.2%). The median time to onset for ILD was 2.8 months (range: 1.1 months to 10.8 months). Four patients (0.9%) had datopotamab deruxtecan-dlnk withheld and 7 patients (1.6%) permanently discontinued therapy due to ILD/pneumonitis. Systemic corticosteroids were required in 60% (9/15) of patients with ILD/pneumonitis. ILD/pneumonitis resolved in 40% of patients.

Patients were excluded from clinical studies 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 datopotamab deruxtecan-dlnk. 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 datopotamab deruxtecan-dlnk in patients with suspected ILD/pneumonitis and permanently discontinue therapy if ≥Grade 2 ILD/pneumonitis is confirmed.

Ocular Adverse Reactions

Datopotamab deruxtecan can cause ocular adverse reactions including dry eye, keratitis, blepharitis, meibomian gland dysfunction, increased lacrimation, conjunctivitis, and blurred vision.

In the pooled safety population, ocular adverse reactions occurred in 36% of patients treated with datopotamab deruxtecan-dlnk. Twenty patients (2.2%) experienced Grade 3 ocular adverse reactions, which included keratitis, dry eye, and blurred vision, and one patient experienced a Grade 4 ocular adverse reaction of conjunctival hemorrhage. The most common (≥5%) ocular adverse reactions were dry eye (17%), keratitis (14%), and increased lacrimation (7%). The median time to onset for ocular adverse reactions was 2.3 months (range: 0.03 months to 23.2 months). Of the patients who experienced ocular adverse reactions, 39% had complete resolution, and 10% 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 dosage interruption in 3.6% of patients, dosage reductions in 2.5% of patients, and permanent discontinuation of therapy in 1% of patients.

Patients with clinically significant corneal disease were excluded from clinical studies.

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 datopotamab deruxtecan, and if diagnosis is confirmed, withhold, reduce the dose, or permanently discontinue datopotamab deruxtecan based on severity.

Stomatitis

Datopotamab deruxtecan can cause stomatitis, including mouth ulcers and oral mucositis.

In the pooled safety population, stomatitis occurred in 63% of patients treated with datopotamab deruxtecan-dlnk, including 8% of patients with Grade 3 events and one patient with a Grade 4 reaction. The median time to first onset of stomatitis was 0.5 months (range: 0.03 months to 18.6 months). Stomatitis led to dosage interruption in 6% of patients, dosage reductions in 11% of patients, and permanent discontinuation of therapy in 0.5% of patients.

In patients who received datopotamab deruxtecan-dlnk in TROPION-Breast01, 39% 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 datopotamab deruxtecan-dlnk.

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, reduce the dose, or permanently discontinue datopotamab deruxtecan-dlnk.

Embryo-fetal Toxicity

Based on its mechanism of action, datopotamab deruxtecan-dlnk can cause embryo-fetal harm when administered to a pregnant woman because the topoisomerase inhibitor component of the drug, DXd, is genotoxic and affects actively dividing cells.

Advise patients of the potential risk to a fetus. Advise female patients of reproductive potential to use effective contraception during treatment with datopotamab deruxtecan-dlnk and for 7 months after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with datopotamab deruxtecan-dlnk and for 4 months after the last dose.

Specific Populations

Pregnancy

Based on its mechanism of action, datopotamab deruxtecan can cause embryo-fetal harm when administered to a pregnant woman because the topoisomerase inhibitor component of the drug, DXd, is genotoxic and affects actively dividing cells. There are no available data on the use of datopotamab deruxtecan-dlnk 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.

Lactation

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 the drug and for 1 month after the last dose.

Females and Males of Reproductive Potential

Datopotamab deruxtecan can cause embryo-fetal harm when administered to a pregnant woman.

Verify pregnancy status of females of reproductive potential prior to initiation of datopotamab deruxtecan-dlnk.

Advise females of reproductive potential to use effective contraception during treatment with datopotamab deruxtecan-dlnk and for 7 months after the last dose.

Because of the potential for genotoxicity, advise male patients with female partners of reproductive potential to use effective contraception during treatment with datopotamab deruxtecan-dlnk and for 4 months after the last dose.

Based on findings in animal toxicity studies, datopotamab deruxtecan may impair male and female reproductive function and fertility. The effects on reproductive organs in animals were irreversible.

Pediatric Use

Safety and effectiveness of datopotamab deruxtecan-dlnk have not been established in pediatric patients.

Geriatric Use

Of the 125 patients with EGFR-mutated NSCLC in TROPION-Lung05, TROPION-Lung01, TROPION-PanTumor01 treated with datopotamab deruxtecan-dlnk 6 mg/kg, 44% were ≥65 years of age and 10% were ≥75 years of age. No clinically meaningful differences in efficacy and safety were observed between patients ≥65 years of age versus younger patients.

Of the 365 patients in TROPION-Breast01 treated with datopotamab deruxtecan-dlnk 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.

Renal Impairment

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). 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. The effect of severe renal impairment (CLcr <30 mL/min) on the pharmacokinetics of datopotamab deruxtecan-dlnk or DXd is unknown.

Hepatic Impairment

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. The recommended dosage of datopotamab deruxtecan-dlnk has not been established for patients with severe hepatic impairment (total bilirubin >3 times ULN and any AST).

Common Adverse Effects

The most common adverse reactions (≥20%), including laboratory abnormalities, in patients with EGFR-mutated NSCLC were stomatitis, nausea, alopecia, fatigue, decreased hemoglobin, decreased lymphocytes, constipation, increased calcium, increased AST, decreased white blood cell count, increased lactate dehydrogenase, musculoskeletal pain, decreased appetite, increased ALT, and rash.

The most common adverse reactions (≥20%), including laboratory abnormalities, in patients with HR-positive, HER2-negative breast cancer 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.

Drug Interactions

Specific Drugs

It is essential that the manufacturer's labeling be consulted for more detailed information on interactions with this drug, including possible dosage adjustments. Interaction highlights:

Please see product labeling for drug interaction information.

Actions

Mechanism of Action

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 Trop-2 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 mouse models of lung cancer including EGFR-mutated and breast cancer.

Advice to Patients

Advise the patient to read the FDA-approved patient labeling (Medication Guide).
Inform patients of the risks of severe or fatal ILD. Advise patients to contact their healthcare provider immediately for any of the following: cough, shortness of breath, fever, or other new or worsening respiratory symptoms.
Inform patients about the need for eye exams at initiation and during treatment with datopotamab deruxtecan-dlnk. Advise patients to contact their healthcare provider if they experience any eye symptoms.
Advise patients to use preservative-free lubricating eye drops several times daily and to avoid use of contact lenses during treatment with datopotamab deruxtecan-dlnk.
Inform patients of the risk of stomatitis. Advise patients to contact their healthcare provider if they experience any symptoms. Inform patients to use a steroid-containing mouthwash for prophylaxis and treatment of stomatitis. Instruct patients to hold ice chips or ice water in their mouth throughout the infusion of datopotamab deruxtecan-dlnk.
Inform female patients of the potential risk to a fetus. Advise female patients to inform their healthcare provider of a known or suspected pregnancy.
Advise females of reproductive potential to use effective contraception during treatment with datopotamab deruxtecan-dlnk and for 7 months after the last dose.
Advise male patients with female partners of reproductive potential to use effective contraception during treatment with datopotamab deruxtecan-dlnk and for 4 months after the last dose.
Advise women not to breastfeed during treatment and for 1 month after the last dose of datopotamab deruxtecan-dlnk.
Advise males and females of reproductive potential that datopotamab deruxtecan-dlnk may impair fertility.

Additional Information

AHFSfirstRelease^™. For additional information until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual uses, dosage and administration, cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.