Datopotamab deruxtecan-dlnk
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Overview
Datopotamab deruxtecan-dlnk is a Trop-2-directed antibody and topoisomerase inhibitor conjugate that is FDA approved for the treatment of EGFR-Mutated Non-Small Cell Lung Cancer (NSCLC). of {{{indication}}}. Common adverse reactions include 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. 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..
Adult Indications and Dosage
FDA-Labeled Indications and Dosage (Adult)
DATROWAY is a Trop-2-directed antibody and topoisomerase inhibitor conjugate indicated for the treatment of:
1. Locally Advanced or Metastatic EGFR-Mutated Non-Small Cell Lung Cancer (NSCLC) DATROWAY 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.
2. Unresectable or Metastatic, HR-Positive, HER2-Negative Breast Cancer 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 me
Recommended Dosage
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.
Premedication, Concomitant Medications, and Required Eye Care
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. Monitor patients for infusion-related reactions in a setting where cardiopulmonary resuscitation medication and equipment are available. Monitor patients 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.
Dosage Modifications
The recommended dose reduction levels for adverse reactions are described below: 1. First dose: 4 mg/kg (up to a maximum of 360 mg for patients ≥90 kg) 2. Second dose:3 mg/kg (up to a maximum of 270 mg for patients ≥90 kg) 3. Third dose: 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.
Off-Label Use and Dosage (Adult)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Datopotamab deruxtecan-dlnk in adult patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Datopotamab deruxtecan-dlnk in adult patients.
Pediatric Indications and Dosage
FDA-Labeled Indications and Dosage (Pediatric)
There is limited information regarding Datopotamab deruxtecan-dlnk FDA-Labeled Indications and Dosage (Pediatric) in the drug label.
Off-Label Use and Dosage (Pediatric)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Datopotamab deruxtecan-dlnk in pediatric patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Datopotamab deruxtecan-dlnk in pediatric patients.
Contraindications
None.
Warnings
Interstitial Lung Disease/Pneumonitis
DATROWAY 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 DATROWAY, 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 DATROWAY withheld and 20 patients (4.1%) permanently discontinued DATROWAY 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 DATROWAY, 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 DATROWAY withheld and 7 patients (1.6%) permanently discontinued DATROWAY due to ILD/pneumonitis. Systemic corticosteroids were required in 60% (9/15) of patients with ILD/pneumonitis. ILD/pneumonitis resolved in 40% of patients.
- 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.
Ócular Adverse Effects
- DATROWAY 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 DATROWAY. 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 DATROWAY in 1% 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.
Stomatitis
- DATROWAY can cause stomatitis, including mouth ulcers and oral mucositis.
- In the pooled safety population, stomatitis occurred in 63% of patients treated with DATROWAY, 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 DATROWAY in 0.5% of patients.
- In patients who received DATROWAY in TROPION-Breast01, 39% used a mouthwash containing corticosteroid for management or prophylaxis of stomatitis/oral mucositis at any time during the treatment.
- Monitor patients for signs and symptoms of stomatitis. If stomatitis occurs, increase the frequency of mouthwash and administer other topical treatments as clinically indicated.
Embryo-Fetal Toxicity
- 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
- 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.
Add table for dosage modifications in this section.
Adverse Reactions
Clinical Trials Experience
Locally Advanced or Metastatic EGFR-Mutated Non-Small Cell Lung Cancer
- The safety of DATROWAY was evaluated in 125 patients with EGFR-mutated NSCLC who received DATROWAY 6 mg/kg administered as an intravenous infusion once every 3 weeks (21-day cycle) until disease progression or unacceptable toxicity in TROPION-Lung05 and TROPION-Lung01 as well as TROPION-PanTumor01 (NCT03401385). Among these patients, the median duration of treatment was 6.1 months (range 0.7 months to 41.7 months).
- The median age was 63 years (range: 36 to 81), 56% of patients were <65 years, 62% of patients were female; 66% were Asian, 26% were White, 0.8% were Black, 6% were other races; and 2.4% were of Hispanic ethnicity.
- Serious adverse reactions occurred in 26% of patients who received DATROWAY. Serious adverse reactions in >1% of patients who received DATROWAY were COVID-19 (4%), stomatitis (2.4%), and pneumonia (1.6%). Fatal adverse reactions occurred in 1.6% of patients who received DATROWAY, due to death not otherwise specified.
- The most common (≥20%) adverse reactions, including laboratory abnormalities, 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 as listed in the table below:
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. 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.
- 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. Add table 6
- 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.
Add table 7.
Postmarketing Experience
There is limited information regarding Levacetylleucine Postmarketing Experience in the drug label.
Drug Interactions
There is limited information regarding Datopotamab deruxtecan-dlnk Drug Interactions in the drug label.
Use in Specific Populations
Pregnancy
Pregnancy Category (FDA): A 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 cell. 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.
Animal Data
- There were no animal reproductive or developmental toxicity studies conducted with datopotamab deruxtecan-dlnk.
Pregnancy Category (AUS):
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Datopotamab deruxtecan-dlnk in women who are pregnant.
Labor and Delivery
There is no FDA guidance on use of Datopotamab deruxtecan-dlnk during labor and delivery.
Nursing Mothers
- 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 DATROWAY and for 1 month after the last dose.
Pediatric Use
Safety and effectiveness of DATROWAY have not been established in pediatric patients.
Geriatic Use
- Of the 125 patients with EGFR-mutated NSCLC in TROPION-Lung05, TROPION-Lung01, TROPION-PanTumor01 treated with DATROWAY 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 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.
Gender
There is no FDA guidance on the use of Datopotamab deruxtecan-dlnk with respect to specific gender populations.
Race
There is no FDA guidance on the use of Datopotamab deruxtecan-dlnk with respect to specific racial populations.
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 [see Dosage and Administration (2.4)]. 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.
Females of Reproductive Potential and Males
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.
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
Immunocompromised Patients
There is no FDA guidance one the use of Datopotamab deruxtecan-dlnk in patients who are immunocompromised.
Administration and Monitoring
Administration
- 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.
Reconstitution
- Reconstitute immediately before dilution.
- More than one vial may be needed for a full dose. Calculate the dose (mg), the total volume of reconstituted DATROWAY solution required, and the number of vial(s) of * DATROWAY needed.
- Reconstitute each 100 mg vial using a sterile syringe to slowly inject 5 mL of Sterile Water for Injection into each vial to obtain a final concentration of 20 mg/mL.
- Swirl the vial gently until completely dissolved. Do not shake.
- If not used immediately, refrigerate the reconstituted DATROWAY solution in the original vial at 2ºC to 8ºC (36°F to 46°F) for up to 48 hours from the time of reconstitution. Protect the vial from light. Do not freeze.
- The product does not contain a preservative. Discard unused reconstituted DATROWAY after 48 hours of refrigeration.
Dilution
- Withdraw the calculated amount from the vial(s) using a sterile syringe. Inspect for particulate matter and discoloration prior to administration. The reconstituted solution should be clear and colorless to light yellow. Do not use if visible particles are observed or if the solution is cloudy or discolored.
- Dilute the calculated volume of reconstituted DATROWAY in an infusion bag containing 100 mL of 5% Dextrose Injection. DO NOT use Sodium Chloride Injection. DATROWAY is compatible with an infusion bag made of polyvinylchloride or polyolefin (polypropylene or copolymer of ethylene and propylene).
- Gently invert the infusion bag to thoroughly mix the solution. Do not shake.
- Cover the infusion bag to protect from light.
- If not used immediately, store at room temperature at up to 25ºC (77°F) for up to 4 hours including preparation or in a refrigerator at 2ºC to 8ºC (36°F to 46°F) for up to 24 hours. Do not freeze.
- Discard any unused portion left in the vial.
Administration
- The maximum time from reconstitution of the vial through the end of administration should not exceed 48 hours. Discard if storage time exceeds these limits.
- If the prepared infusion solution was stored refrigerated at 2ºC to 8ºC (36°F to 46°F), allow the solution to reach room temperature prior to administration, protected from light.
- Inspect for particulate matter and discoloration prior to administration.
- Administer DATROWAY as an intravenous infusion only with an infusion line and tubing set made of polyvinyl chloride, polybutadiene or low-density polyethylene.
- Administer DATROWAY with a 0.2-micron in-line polytetrafluoroethylene, polyethersulfone or nylon 66 filter.
- Do NOT administer as an intravenous push or bolus.
- Cover the infusion bag to protect from light during administration.
- Do not mix DATROWAY with other drugs or administer other drugs through the same intravenous line.
- Instruct the patient to hold ice chips or ice water in the mouth throughout the infusion of DATROWAY.
First infusion: Administer 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. Second Infusion: If first infusion was tolerated, administer second infusion over 30 minutes. Observe patients during the infusion and for at least 1 hour after infusion. Subsequent Infusions: Administer infusion over 30 minutes if prior infusions were tolerated. Observe patients during the infusion and for at least 30 min after infusion.
Monitoring
Monitoring for Datroway and management for adverse reactions is listed in the table below:
Table 3
IV Compatibility
There is limited information regarding the compatibility of Datopotamab deruxtecan-dlnk and IV administrations.
Overdosage
There is limited information regarding Datopotamab deruxtecan-dlnk overdosage. If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.
Pharmacology
There is limited information regarding Datopotamab deruxtecan-dlnk Pharmacology in the drug label.
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.
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.
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Pharmacodynamics
- 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 or EGFR-mutated NSCLC.
- In the pooled population of NSCLC (including EGFR-mutated NSCLC) and breast cancer patients, 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.
Cardiac Electrophysiology
- At datopotamab deruxtecan-dlnk doses up to 10 mg/kg (1.7 times the recommended dose), mean increase in the QTc interval >20 ms was not observed.
Pharmacokinetics
- Datopotamab deruxtecan-dlnk and DXd exposure after the first dose of the approved recommended dosage of cycle 1 are provided in Table 8. 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.
Table 8
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.
Immunogenicity There is insufficient information from TROPION-Breast01, TROPION-Lung01, and TROPION-Lung05 to characterize the anti-drug antibody response to datopotamab deruxtecan-dlnk and the effects of anti-drug antibodies on pharmacokinetics, pharmacodynamics, safety, or effectiveness of datopotamab deruxtecan-dlnk products.
Nonclinical Toxicology
Carcinogenesis, Mutagenesis, Impairment of Fertility
- 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.
Clinical Studies
Locally Advanced or Metastatic EGFR-Mutated Non-Small Cell Lung Cancer
- The efficacy of DATROWAY was evaluated in a pooled subgroup of patients with locally advanced or metastatic EGFR-mutated NSCLC who were enrolled across two clinical studies: TROPION-Lung05 and TROPION-Lung01.
- TROPION-Lung05 (NCT04484142) was a global, multicenter, single-arm, open-label trial in patients with previously treated NSCLC with an actionable genomic alteration and TROPION-Lung01 (NCT04656652) was a global, multicenter, randomized, active-controlled, open-label trial in patients with previously treated NSCLC with or without an actionable genomic alteration. For both trials, eligible patients with EGFR-mutated NSCLC must have previously received an EGFR-directed therapy and platinum-based chemotherapy. Patients with a history of ILD/pneumonitis requiring treatment with steroids, ongoing ILD/pneumonitis, or clinically significant corneal disease at screening were ineligible. Patients who had brain metastases that were untreated and symptomatic were also ineligible. Patients received DATROWAY 6 mg/kg by intravenous infusion every 3 weeks until unacceptable toxicity or disease progression.
- For the pooled efficacy population, the major efficacy outcome measure was overall response rate (ORR) by BICR per RECIST v1.1. An additional efficacy outcome was duration of response (DOR) by BICR.
- Efficacy was assessed in 114 patients with EGFR-mutated NSCLC. The median age was 63 years (range 36 to 81); 43% were ≥65 years of age; 63% were female; 70% were Asian and 22% were White; 1.8% were of Hispanic/Latino ethnicity; 68% had ECOG PS of 1 and 32% had ECOG PS of 0; and 33% had brain metastases at baseline. Fifty-three percent (53%) of patients had tumors with exon 19 deletions, 34% had exon 21 L858R mutations, 28% had T790M mutations, 2.6% had exon 20 insertion mutations and 14% had other EGFR mutations. Four percent (4.4%) of patients received one prior line of systemic therapy, 39% received two prior lines of systemic therapy, and 57% received three or more prior lines of systemic therapy in the locally advanced or metastatic setting. All patients received prior EGFR-directed therapy including 84% receiving prior osimertinib; 99% received prior platinum-based chemotherapy and 28% received prior anti-PD-1/ PD-L1 therapy.
Add table 9
Unresectable or Metastatic, HR-Positive, HER2-Negative Breast Cancer 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.
Table 10
How Supplied
How Supplied
- DATROWAY (datopotamab deruxtecan-dlnk) for injection is a white to yellowish white lyophilized powder supplied as:
- Carton Contents : One 100 mg single-dose vial
- NDC : NDC 65597-801-01
Storage
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.
- DATROWAY (datopotamab deruxtecan-dlnk) is a hazardous drug. Follow applicable special handling and disposal procedures.
Images
Drug Images
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Package and Label Display Panel
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Patient Counseling Information
Advise the patient to read the FDA-approved patient labeling (Medication Guide).
Interstitial Lung Disease/Pneumonitis
- 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.
Ocular Adverse Reactions
- Inform patients about the need for eye exams at initiation and during treatment with DATROWAY .
- 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 DATROWAY.
Stomatitis
- 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 DATROWAY.
Embryo-Fetal Toxicity
- 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 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.
Lactation
Advise women not to breastfeed during treatment and for 1 month after the last dose of DATROWAY .
Infertility
- Advise males and females of reproductive potential that DATROWAY may impair fertility.
Precautions with Alcohol
Alcohol-Datopotamab deruxtecan-dlnk interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
Brand Names
DATROWAY
Look-Alike Drug Names
There is limited information regarding Levacetylleucine Look-Alike Drug Names in the drug label.
Price
References
The contents of this FDA label are provided by the National Library of Medicine.