Datopotamab deruxtecan-dlnk, a trophoblast cell-surface antigen-2 (Trop-2)-directed antibody-drug conjugate consisting of a humanized IgG1 monoclonal antibody covalently linked to a type I DNA topoisomerase inhibitor DXd (an exatecan derivative), is an antineoplastic agent.1
Datopotamab deruxtecan-dlnk is used 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.1
The accelerated approval for this indication is based on objective response rate and duration of response.1 Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trial.1
Previously Treated Locally Advanced or Metastatic EGFR-mutated Non-small Cell Lung Cancer
The safety and efficacy of datopotamab deruxtecan-dlnk for this indication were principally established in 2 clinical trials: a phase 2, multicenter, single-arm, open-label trial in previously-treated adult patients with advanced or metastatic NSCLC with an actionable genomic alteration (TROPION-Lung05), and a phase 3, multicenter, randomized, active-controlled, open-label trial in previously treated adult patients with NSCLC with or without an actionable genomic alteration (TROPION-Lung01).1, 2, 3 Patients were excluded if they had a history of interstitial lung disease (ILD) or pneumonitis requiring treatment with steroids, ongoing ILD/pneumonitis, clinically significant corneal disease at screening, or clinically active CNS metastases (untreated and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control symptoms).1, 2, 3 Datopotamab deruxtecan-dlnk was administered as a 6 mg/kg IV infusion every 3 weeks (on Day 1 of each 21-day cycle) until unacceptable toxicity or disease progression.1, 2, 3 The primary efficacy endpoint was overall response rate, defined as those who achieved either a complete or partial response, as assessed by blinded independent central review (BICR) per RECIST v1.1; duration of response, as assessed by BICR per RECIST v1.1, was an additional efficacy outcome.1, 2, 3
Efficacy was evaluated in a pooled subgroup that included 114 patients with EGFR-mutated NSCLC from TROPION-Lung05 and TROPION-Lung01.1 The median age was 63 years (range: 36-81 years); the majority were female (63%).1 Most patients were Asian (70%); 22% were White.1 At baseline, the Eastern Cooperative Oncology Group (ECOG) performance status was 0 in 32% of patients and 1 in 68% of patients; 33% of patients had brain metastases.1 With regard to EGFR mutation type, 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.1 The majority of patients received ≥3 prior lines of systemic therapy (57%) in the locally advanced or metastatic setting.1 All patients received prior EGFR-directed therapy, most commonly osimertinib (84%); 99% received prior platinum-based chemotherapy and 28% received prior anti-programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) therapy.1
In the pooled efficacy population, the overall response rate was 45%, with 4.4% of patients achieving a complete response and 40% achieving a partial response.1 In TROPION-Lung05, a difference was noted between the overall response rate by BICR (45%) and overall response rate by investigator review (34%).1 In TROPION-Lung01, the overall response rate by BICR and the overall response rate by investigator review were similar.1 In the pooled efficacy population, the median duration of response was 6.5 months; 47% of patients had sustained responses at 6 months and 18% had sustained responses at 12 months.1
EGFR-activating mutations are present in approximately 15-22% of NSCLC cases in North America and Europe and in up to 30-50% of cases in patients of East Asian descent.5 The majority of EGFR mutations are exon 19 deletions and an L858R substitution in exon 21, which together account for about 90% of EGFR mutations in patients with NSCLC.101 EGFR mutations are identified in a large proportion of NSCLC cases in nonsmokers (49.3%), female patients (43.7%), and those with adenocarcinoma histology (38%).102
The American Society of Clinical Oncology (ASCO) 2026 guideline specifically addresses treatment of stage IV NSCLC harboring driver alterations such as EGFR mutations.103 Treatment recommendations are tailored to the specific EGFR mutation (exon 19 deletion, exon 21 L858R substitution, or exon 20 insertion) and based on the previously trialed therapy.103 Several treatment regimens are recommended in the second-line setting and beyond.103 Datopotamab deruxtecan-dlnk is recommended as a treatment option for patients with exon 19 deletion or exon 21 L858R substitution whose disease has progressed on osimertinib and platinum chemotherapy.103
Datopotamab deruxtecan-dlnk is used for the treatment of adult patients with unresectable or metastatic triple-negative breast cancer (TNBC) who are not candidates for PD-1/PD-L1 inhibitor therapy.1
Datopotamab deruxtecan-dlnk is also used 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
Unresectable or Metastatic Triple-negative Breast Cancer
The safety and efficacy of datopotamab deruxtecan-dlnk for this indication are based principally on the results of a phase 3, randomized, open-label trial (TROPION-Breast02).1 Patients with unresectable or metastatic triple-negative breast cancer (de novo metastatic or recurrent disease) were included if they had not received prior chemotherapy or other systemic anti-cancer therapy for unresectable or metastatic breast cancer, and if they had PD-L1 negative tumors or PD-L1-positive tumors but were ineligible for PD-1/PD-L1 inhibitor treatment.1 Patients with recurrent disease were expected to have been treated with neoadjuvant anthracycline; patients with de novo metastatic disease were included if treatment with anthracycline was contraindicated or considered not the best treatment option.1 Patients with known germline BRCA pathogenic variants were included if they were ineligible for poly(ADP-ribose) (PARP) inhibitor therapy.1 Patients were excluded if they had a history of ILD or pneumonitis requiring treatment with steroids, ongoing ILD/pneumonitis, clinically significant corneal disease at screening, or an ECOG performance status >1.1 Patients were randomized 1:1 to receive datopotamab deruxtecan-dlnk 6 mg/kg IV infusion every 3 weeks (on Day 1 of each 21-day cycle) or an investigator's choice of chemotherapy (paclitaxel, nab-paclitaxel, capecitabine, eribulin, or carboplatin) until unacceptable toxicity or disease progression.1 The choice of chemotherapy was based on the patient's prior use of taxane and disease-free interval history.1 The primary efficacy endpoints were progression-free survival (PFS) as assessed by BICR per RECIST v1.1 and overall survival (OS).1 Objective response rate, as assessed by BICR per RECIST v1.1, was a secondary efficacy outcome.1
A total of 644 patients were randomized and included in the efficacy population.1 The median age was 56 years (range: 23-85 years); 25% were ≥65 years of age.1 The majority were female (99.7%); 44% were White, 44% were Asian, and 4.2% were Black.1 At baseline, 59% had an ECOG performance status of 0 and 41% had an ECOG performance status of 1.1 Most patients had visceral disease (75%); 30% had liver metastases and 10% had stable brain metastases.1 Thirty-four percent (34%) of patients had de novo metastatic disease.1 The majority of patients (90%) had PD-L1 negative disease.1 The disease-free interval was >12 months in 45% of patients, ≤12 months in 21% of patients, and ≤6 months in 15% of patients.1 The majority of patients (56%) received anthracyclines in prior lines of therapy.1
Median PFS was 10.8 months in datopotamab deruxtecan-dlnk-treated patients compared to 5.6 months in the investigator's choice chemotherapy group.1 Median OS was 23.7 months in datopotamab deruxtecan-dlnk-treated patients compared to 18.7 months in the investigator's choice chemotherapy group.1 Objective response rate was 64% and 30%, respectively, in datopotamab deruxtecan-dlnk-treated and investigator's choice chemotherapy patients.1 Of the patients who responded, 56% and 8% of the datopotamab deruxtecan-dlnk cohort achieved a partial or complete response, respectively; 28% and 3% of the investigator's choice cohort achieved a partial or complete response, respectively.1
Unresectable or Metastatic HR-positive, HER2-negative Breast Cancer
The safety and efficacy of datopotamab deruxtecan-dlnk for this indication are based principally on the results of a phase 3, randomized, open-label trial (TROPION-Breast01).1, 4 Patients with unresectable or metastatic HR-positive, HER2-negative (immunohistochemistry [IHC] 0, IHC1+, or IHC2+/in situ hybridization [ISH]-) breast cancer were included if they had progressed on and were deemed not suitable for further endocrine therapy, and if they had received 1 or 2 lines of prior chemotherapy in the unresectable or metastatic setting.1, 4 Patients were excluded if they had a history of ILD or pneumonitis requiring treatment with steroids, ongoing ILD/pneumonitis, clinically significant corneal disease at screening, clinically active brain metastases, or an ECOG performance status >1.1, 4 Patients were randomized 1:1 to receive datopotamab deruxtecan-dlnk 6 mg/kg IV infusion every 3 weeks (on Day 1 of each 21-day cycle) or an investigator's choice of chemotherapy (e.g., eribulin, capecitabine, vinorelbine, or gemcitabine) until unacceptable toxicity or disease progression.1, 4 The primary efficacy endpoints were PFS as assessed by BICR per RECIST v1.1 and OS.1, 4 Objective response rate and duration of response, as assessed by BICR per RECIST v1.1, were key secondary efficacy outcomes.1, 4
A total of 732 patients were randomized and included in the efficacy population.1, 4 The median age was 55 years (range: 28-86 years); 22% were ≥65 years of age.1, 4 The majority were female (99%); 48% were White, 41% were Asian, and 1.5% were Black.1, 4 At baseline, 57% had an ECOG performance status of 0 and 42% had an ECOG performance status of 1.1, 4 Most patients had visceral disease (97%); 72% had liver metastases, and 8% had stable brain metastases.1, 4 The majority of patients (60%) received prior endocrine therapy in the neoadjuvant setting and 89% received prior endocrine therapy in the unresectable or metastatic setting.1, 4
Median PFS was 6.9 months in datopotamab deruxtecan-dlnk-treated patients compared to 4.9 months among the patients administered investigator's choice of chemotherapy.1, 4 Median OS was 18.6 months in datopotamab deruxtecan-dlnk-treated patients compared to 18.3 months in the investigator's choice cohort.1, 4 Objective response rate was 36% and 23%, respectively, in datopotamab deruxtecan-dlnk-treated patients and chemotherapy-treated patients.1, 4 Of the patients who responded, 36% and 0.5% of the datopotamab deruxtecan-dlnk cohort achieved a partial or complete response, respectively; 23% of the investigator's choice chemotherapy cohort achieved a partial response and no patients achieved a complete response.1, 4 The median duration of response was 6.7 months for datopotamab deruxtecan-dlnk-treated patients and 5.7 months for those administered the investigator's choice of chemotherapy.1, 4
Unresectable or Metastatic Triple-negative Breast Cancer
Guidelines from the American Society of Clinical Oncology (ASCO) provide recommendations for the treatment of metastatic triple-negative breast cancer.104 Treatment recommendations are tailored to specific mutations and based on previously trialed therapy, as applicable.104 In the first-line setting, chemotherapy is recommended in the absence of PD-L1 mutation.104 If PD-L1 mutation is present, an immune checkpoint inhibitor, such as atezolizumab or pembrolizumab, may be added to a chemotherapy regimen.104 In the second-line setting, taxane- or platinum-based single-agent chemotherapy is recommended; metronomic chemotherapy may be considered.104 In the third-line setting and beyond, single-agent chemotherapy is recommended.104 Datopotamab deruxtecan-dlnk is not discussed in the guidelines as the drug was approved after publication of the last guideline update.104
Unresectable or Metastatic HR-positive, HER2-negative Breast Cancer
Guidelines from the American Society of Clinical Oncology (ASCO) provide recommendations for the treatment of metastatic HR-positive, HER2-negative breast cancer.104 Treatment recommendations are tailored to specific mutations, and are based on menopause status and previously trialed therapy, as applicable.104 In the first-line setting, treatment options generally include sequential hormone therapy, nonsteroidal aromatase inhibitors, and/or CDK4/6 inhibitors, depending on patient-specific factors.104 Several treatment regimens are recommended in the second-line or later setting based on various factors such as PIK3CA mutation status, BRCA mutation status, and response to previous therapies.104 Datopotamab deruxtecan-dlnk is not discussed in the guidelines as the drug was approved after publication of the last guideline update.104
Premedication | Examples (or equivalent) | Timing of Treatment/Duration |
|---|---|---|
Eye drops | Preservative-free lubricant eye drops | Administer ≥4 times daily and as needed |
Mouthwash | Steroid-containing mouthwash (dexamethasone oral solution 0.1 mg/mL) | Administer 4 times daily and as needed |
Antihistamine | Diphenhydramine (25-50 mg) administered IV or orally | Administer 30-60 minutes prior to each infusion |
Antipyretic | Acetaminophen (650-1000 mg) administered IV or orally | Administer 30-60 minutes prior to each infusion |
Antiemetics | 5-HT3 serotonin receptor antagonist or appropriate alternatives IV or orally | Administer prior to each infusion and thereafter as needed |
Dispensing and Administration Precautions
Administer datopotamab deruxtecan-dlnk via IV infusion in a dedicated line with a low protein-binding 0.2-micron in-line filter.1 Do not administer via rapid IV bolus injection.1
Instruct patients to hold ice chips or ice water in their mouth throughout the infusion.1
Datopotamab deruxtecan-dlnk is available as a 100 mg single-dose vial of preservative-free lyophilized powder that must be reconstituted and diluted prior to IV infusion.1
Do not administer in the same IV line with other medications.1
Cover the infusion bag to protect from light during administration.1
Store vials of datopotamab deruxtecan-dlnk refrigerated at 2-8°C in the original carton.1 Do not freeze.1
Datopotamab deruxtecan-dlnk is compatible with 5% dextrose injection.1
Determine the number of datopotamab deruxtecan-dlnk vials needed to obtain the appropriate dose according to the patient's body weight.1
Reconstitute each 100-mg vial with 5 mL of sterile water for injection.1 The concentration of each reconstituted vial should be 20 mg/mL.1 Swirl the vial gently until completely dissolved; do not shake.1
Inspect the reconstituted solution for particulate matter and discoloration.1 The reconstituted product should be clear and colorless to light yellow with no visible particles.1 Discard if any particulate matter or discoloration is observed.1
The reconstituted solution should be used immediately, or stored in the refrigerator (2-8°C) for ≤48 hours.1 Protect the vial from light.1
Following reconstitution, withdraw the necessary volume for the calculated dose from each vial and slowly add to a polyvinyl chloride (PVC) or polyolefin infusion bag containing 100 mL of 5% dextrose injection.1 Do not use sodium chloride injection.1 Discard any unused reconstituted solution remaining in vials.1
Gently invert the infusion bag to mix.1 Do not shake.1
Do not use if the diluted solution is discolored or particles are observed.1
Cover the infusion bag to protect from light.1
Store the prepared datopotamab deruxtecan-dlnk solution at room temperature (≤25°C) for ≤4 hours (including preparation time) or in the refrigerator (2-8°C) for ≤24 hours.1 Do not freeze.1
Administer the first dose via IV infusion over 90 minutes.1
Administer the second dose via IV infusion over 30 minutes.1
Administer subsequent doses via IV infusion over 30 minutes, if previous infusions were tolerated.1
Temporary interruption or infusion rate reduction may be necessary for patients who experience infusion-related reactions.1
Previously Treated Locally Advanced or Metastatic EGFR-mutated Non-small Cell Lung Cancer
For the treatment of previously treated locally advanced or metastatic EGFR-mutated non-small cell lung cancer, the recommended adult dosage of datopotamab deruxtecan-dlnk is 6 mg/kg (up to a maximum of 540 mg for patients ≥90 kg) as an IV infusion every 3 weeks (21-day cycle).1 Therapy should be continued until disease progression or unacceptable toxicity occurs.1
If a planned dose is delayed or missed, administer as soon as possible; do not wait until the next planned cycle.1 Adjust the schedule of administration to maintain a 3-week interval between doses.1
Unresectable or Metastatic Triple-negative Breast Cancer
For the treatment of unresectable or metastatic triple-negative breast cancer, the recommended adult dosage of datopotamab deruxtecan-dlnk is 6 mg/kg (up to a maximum of 540 mg for patients ≥90 kg) as an IV infusion every 3 weeks (21-day cycle).1 Therapy should be continued until disease progression or unacceptable toxicity occurs.1
If a planned dose is delayed or missed, administer as soon as possible; do not wait until the next planned cycle.1 Adjust the schedule of administration to maintain a 3-week interval between doses.1
Unresectable or Metastatic HR-positive, HER2-negative Breast Cancer
For the treatment of unresectable or metastatic HR-positive, HER2-negative breast cancer, the recommended adult dosage of datopotamab deruxtecan-dlnk is 6 mg/kg (up to a maximum of 540 mg for patients ≥90 kg) as an IV infusion every 3 weeks (21-day cycle).1 Therapy should be continued until disease progression or unacceptable toxicity occurs.1
If a planned dose is delayed or missed, administer as soon as possible; do not wait until the next planned cycle.1 Adjust the schedule of administration to maintain a 3-week interval between doses.1
Dosage Modification for Toxicity
If adverse events occur during therapy, temporary interruption, dosage reduction, and/or discontinuance of datopotamab deruxtecan-dlnk may be necessary.1 If dosage reduction is necessary, an initial reduction to 4 mg/kg (up to a maximum of 360 mg for patients ≥90 kg) is recommended.1 If further dosage reduction is necessary, the dosage should be reduced to 3 mg/kg (up to a maximum of 270 mg for patients ≥90 kg).1 If a dosage of 3 mg/kg is not tolerated, datopotamab deruxtecan-dlnk should be permanently discontinued.1 Once the dosage has been reduced for adverse reactions, do not subsequently increase the dose of datopotamab deruxtecan-dlnk.1
Interstitial Lung Disease (ILD)/Pneumonitis
If Grade 1 (asymptomatic) ILD/pneumonitis occurs, withhold datopotamab deruxtecan-dlnk until ILD/pneumonitis is completely resolved.1 If resolved in ≤28 days, maintain current dose.1 If resolved in >28 days, reduce 1 dose level.1 Consider corticosteroids as soon as ILD/pneumonitis is suspected.1
If Grade ≥2 (symptomatic) ILD/pneumonitis occur, permanently discontinue datopotamab deruxtecan-dlnk.1 Administer corticosteroids as soon as ILD/pneumonitis is suspected.1
If nonconfluent superficial keratitis occurs, monitor the patient.1 Continue datopotamab deruxtecan-dlnk at current dose.1
If confluent superficial keratitis, a cornea epithelial defect, or ≥3-line loss in best corrected visual acuity occurs, withhold datopotamab deruxtecan-dlnk until symptoms improve or resolve.1 Restart datopotamab deruxtecan-dlnk at the same dose level, or consider dose reduction.1
If corneal ulcer, stromal opacity, or best corrected distance visual acuity 20/200 or worse occurs, withhold datopotamab deruxtecan-dlnk until symptoms improve or resolve.1 Restart datopotamab deruxtecan-dlnk at a reduced dose level.1
If corneal perforation occurs, permanently discontinue datopotamab deruxtecan-dlnk.1
If Grade 1 stomatitis occurs, optimize prophylactic and supportive medications.1 Continue datopotamab deruxtecan-dlnk at current dose.1
If Grade 2 stomatitis occurs, withhold datopotamab deruxtecan-dlnk until stomatitis resolves to Grade ≤1.1 For the first occurrence, restart datopotamab deruxtecan-dlnk at the same dose level.1 For recurrence, consider restarting at a reduced dose level.1
If Grade 3 stomatitis occurs, withhold datopotamab deruxtecan-dlnk until stomatitis resolves to Grade ≤1.1 Restart datopotamab deruxtecan-dlnk at a reduced dose level.1
If Grade 4 stomatitis occurs, permanently discontinue datopotamab deruxtecan-dlnk.1
Infusion-related Reactions (IRR)
If Grade 1 IRR occurs, reduce datopotamab deruxtecan-dlnk infusion rate by 50% and monitor patient closely.1
If Grade 2 IRR occurs, interrupt datopotamab deruxtecan-dlnk infusion and administer supportive care medications.1 If the IRR resolves or improves to Grade 1, restart the infusion at 50% of the original rate.1 Administer all subsequent infusions at the reduced rate.1
If Grade 3 or 4 IRR (including anaphylactic reactions) occurs, permanently discontinue datopotamab deruxtecan-dlnk.1
Other Non-hematologic Adverse Reactions
If Grade 3 occurs, withhold datopotamab deruxtecan-dlnk until resolved to Grade ≤1 or baseline.1 Restart datopotamab deruxtecan-dlnk at a reduced dose level.1
If Grade 4 occurs, permanently discontinue datopotamab deruxtecan-dlnk.1
In patients with mild (total bilirubin ≤ the upper limit of normal [ULN] and any AST>ULN or total bilirubin >1-1.5 times ULN and any AST) or moderate (total bilirubin >1.5-3 times ULN and any AST) hepatic impairment, no dosage adjustment is necessary.1
The manufacturer makes no specific dosage recommendations for patients with severe hepatic impairment (total bilirubin >3 times ULN and any AST).1
In patients with renal impairment (Clcr 30-<90 mL/minute), no dosage adjustment is necessary.1
The manufacturer makes no specific dosage recommendations for patients with severe renal impairment (CLcr<30 mL/minute).1
The manufacturer makes no specific dosing recommendations for geriatric patients.1
Interstitial Lung Disease/Pneumonitis
Datopotamab deruxtecan-dlnk can cause severe, life-threatening, or fatal ILD or pneumonitis.1 In clinical studies, patients with a history of ILD/pneumonitis requiring treatment with steroids or those with ongoing ILD/pneumonitis were excluded.1
In a pooled safety analysis of patients with NSCLC treated with datopotamab deruxtecan-dlnk, ILD/pneumonitis occurred in 7% of patients.1 Of those, 0.6% of cases were Grade 3 and 0.4% were Grade 4; 8 cases (1.7%) were fatal.1 Systemic corticosteroids were required in 79% of patients.1 The median time to first onset was 1.4 months (range: 0.2-9 months).1 Datopotamab deruxtecan-dlnk was withheld in 11 patients (2.3%) and permanently discontinued in 20 patients (4.1%) due to ILD/pneumonitis.1 ILD/pneumonitis resolved in 45% of patients.1
In a pooled safety analysis of patients with breast cancer treated with datopotamab deruxtecan-dlnk, ILD/pneumonitis occurred in 3% of patients.1 Of those, 0.4% of cases were Grade 3; 2 cases (0.2%) were fatal.1 Systemic corticosteroids were required in 64% of patients.1 The median time to first onset was 5.3 months (range: 1.1-19.3 months), and the median duration was 1.2 months (range: 0.3-5.2 months).1 Datopotamab deruxtecan-dlnk was withheld in 8 patients (1%) and permanently discontinued in 10 patients (1.2%) due to ILD/pneumonitis.1 ILD/pneumonitis resolved in 40% of patients.1
Monitor patients for new or worsening respiratory symptoms indicative of ILD/pneumonitis (e.g., dyspnea, cough, fever) during treatment.1 For Grade 1 (asymptomatic) ILD/pneumonitis, consider corticosteroid treatment (e.g., ≥0.5 mg/kg/day prednisolone or equivalent).1 For Grade ≥2 (symptomatic) ILD/pneumonitis, promptly initiate systemic corticosteroid treatment (e.g., ≥1 mg/kg/day prednisolone or equivalent) and continue for ≥14 days, followed by a gradual taper for at least 4 weeks.1
Withhold datopotamab deruxtecan-dlnk in patients with suspected ILD/pneumonitis and permanently discontinue if Grade ≥2 ILD/pneumonitis is confirmed.1
Datopotamab deruxtecan-dlnk can cause ocular adverse reactions including dry eye, keratitis, blepharitis, meibomian gland dysfunction, increased lacrimation, conjunctivitis, and blurred vision.1 In clinical studies, patients with clinically significant corneal disease were excluded.1 In a pooled safety analysis, 38% of patients experienced ocular adverse reactions.1 Of those, 3.1% of cases were Grade 3 (keratitis, dry eye); 0.3% of cases were Grade 4 (keratitis, corneal epithelium defect, corneal lesion, and conjunctival hemorrhage).1 The most common (≥5%) ocular adverse reactions were dry eye (18%), keratitis (16%), increased lacrimation (6%), and conjunctivitis (5%).1 The median time to first onset of ocular adverse reactions was 2.3 months (range: 0.03-30 months), and the median duration was 2.3 months (range: 0.03-19.5 months).1 Datopotamab deruxtecan-dlnk therapy was interrupted in 4.3% of patients, dosage was reduced in 2.8% of patients, and permanently discontinued in 0.9% of patients due to ocular adverse reactions.1 Ocular adverse reactions completely resolved in 39% of patients, and 8% had partial improvement (defined as a decrease in severity by ≥1 grade from the worst grade at last follow up).1
Advise patients to use preservative-free lubricant eye drops ≥4 times daily and as needed for prophylaxis.1 Advise patients to avoid use of contact lenses unless directed by an eye care professional.1
Refer patients to an eye care professional for an ophthalmic exam including visual acuity testing, slit lamp examination (with fluorescin staining), intraocular pressure, and fundoscopy at treatment initiation, at end of treatment, and as clinically indicated.1 While on treatment, conduct visual acuity testing and slit lamp examination every 3 cycles.1
Promptly refer patients to an eye care professional for any new or worsening ocular adverse reactions.1 Monitor patients for ocular adverse reactions during treatment.1 If diagnosis is confirmed, withhold, reduce dosage, or permanently discontinue datopotamab deruxtecan-dlnk based on severity.1
Datopotamab deruxtecan-dlnk can cause stomatitis, including mouth ulcers and oral mucositis.1 In a pooled safety analysis, 63% of patients experienced stomatitis.1 Of those, 8% of cases were Grade 3; 1 case was Grade 4.1 The median time to first onset of stomatitis was 0.5 months (range: 0.03-19.8 months), and the median duration was 1.1 months (range: 0.03-33.2 months).1 Datopotamab deruxtecan-dlnk therapy was interrupted in 5% of patients, dosage was reduced in 11% of patients, and therapy was permanently discontinued in 0.4% of patients.1
Advise patients to use a steroid-containing mouthwash for prophylaxis and treatment of stomatitis.1 Instruct the patient to hold ice chips or ice water in the mouth throughout the datopotamab deruxtecan-dlnk infusion.1
Monitor patients for signs and symptoms of stomatitis.1 If stomatitis occurs, increase the frequency of mouthwash and administer other topical treatments as clinically indicated; withhold, reduce dosage, or permanently discontinue datopotamab deruxtecan-dlnk based on severity.1
Fetal/Neonatal Morbidity and Mortality
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, deruxtecan-dlnk, is genotoxic and affects actively dividing cells.1
Advise female patients of the potential risk to a fetus.1 Advise female patients of reproductive potential to use effective contraception during treatment with datopotamab deruxtecan-dlnk and for 7 months after the last dose.1 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.1
There are no human or animal data on datopotamab deruxtecan-dlnk use in pregnant women.1 However, based on its mechanism of action, datopotamab deruxtecan-dlnk can cause fetal harm when administered to a pregnant woman because the topoisomerase inhibitor component, deruxtecan-dlnk, is genotoxic and affects actively dividing cells.1
Verify the pregnancy status of females of reproductive potential prior to the initiation of datopotamab deruxtecan-dlnk.1 Advise pregnant women and females of reproductive potential that exposure to datopotamab deruxtecan-dlnk during pregnancy can result in fetal harm.1
It is not known whether datopotamab deruxtecan-dlnk is distributed into human milk.1 Effects of the drug on breastfed infants or milk production are also not known.1 However, because of the potential for serious adverse reactions in a breastfed child, advise women not to breastfeed during treatment with datopotamab deruxtecan-dlnk and for 1 month after the last dose.1
Females and Males of Reproductive Potential
Datopotamab deruxtecan-dlnk can cause embryo-fetal harm when administered to a pregnant woman.1 Verify the pregnancy status of females of reproductive potential prior to the initiation of datopotamab deruxtecan-dlnk.1 Advise pregnant women and females of reproductive potential that exposure to datopotamab deruxtecan-dlnk during pregnancy can result in fetal harm.1
Advise females of reproductive potential to use effective contraception while receiving datopotamab deruxtecan-dlnk and for 7 months after the last dose.1
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.1
Based on animal data, datopotamab deruxtecan-dlnk may impair male and female reproductive function and fertility.1 The effects on reproductive organs in animals were irreversible.1
Safety and efficacy of datopotamab deruxtecan-dlnk have not been established in pediatric patients <18 years of age.1
In clinical studies of patients with EGFR-mutated NSCLC, 44% of 125 patients were ≥65 years of a 10% were ≥75 years of age.1 No overall differences in safety or efficacy were observed between geriatric patients (≥65 years of age) and younger adults (<65 years of age).1
In clinical studies of patients with breast cancer, 23% of 841 patients were ≥65 years of a 4.5% were ≥75 years of age.1 Grade ≥3 and serious adverse reactions were more common in patients ≥65 years of age (45% and 22%, respectively) compared to younger adults <65 years of age (38% and 16%, respectively).1 No other differences in safety or efficacy were observed between geriatric patients (≥65 years of age) and younger adults (<65 years of age).1
Monitor patients with moderate hepatic impairment (total bilirubin >1.5-3 times the upper limit of normal [ULN] and any AST) for increased adverse reactions; limited data are available in this population.1 Mild hepatic impairment (total bilirubin ≤ULN and AST >ULN, or total bilirubin between 1-1.5 times ULN and any AST) does not have a clinically important effect on the pharmacokinetics of datopotamab deruxtecan-dlnk.1 The effects of severe hepatic impairment (total bilirubin >3 times the ULN and any AST) on datopotamab deruxtecan-dlnk pharmacokinetics have not been studied.1
Monitor patients with renal impairment (Clcr 30-<90 mL/minute [estimated by Cockcroft Gault]) for increased adverse reactions, including respiratory reactions; a higher incidence of ILD/pneumonitis has been observed.1 The effects of severe renal impairment (Clcr<30 mL/minute) on datopotamab deruxtecan-dlnk pharmacokinetics have not been studied.1
The most common adverse reactions (incidence ≥20%), including laboratory abnormalities, reported with datopotamab deruxtecan-dlnk 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.1
The most common adverse reactions (incidence ≥20%), including laboratory abnormalities, reported with datopotamab deruxtecan-dlnk in patients with triple-negative breast cancer were stomatitis, increased amylase, nausea, alopecia, decreased hemoglobin, decreased white blood cells, constipation, decreased calcium, decreased lymphocytes, fatigue, decreased neutrophils, increased ALT, increased AST, dry eye, keratitis, decreased albumin, vomiting, musculoskeletal pain, decreased sodium, and increased blood alkaline phosphatase.1
The most common adverse reactions (incidence ≥20%), including laboratory abnormalities, reported with datopotamab deruxtecan-dlnk 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.1
No formal drug interaction studies have been performed with datopotamab deruxtecan-dlnk; however, pharmacokinetic interactions with DXd, the topoisomerase I inhibitor component of the antibody-drug conjugate, have been studied with a DXd-containing antibody-drug conjugate similar in structure to datopotamab deruxtecan-dlnk.1 No clinically significant differences in DXd pharmacokinetics were predicted when used concomitantly with a strong cytochrome P-450 (CYP) isoenzyme 3A (itraconazole) or a dual organic anion transporting polypeptide (OATP) 1B and CYP3A inhibitor (ritonavir).1
In vitro studies indicate that DXd does not inhibit CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, or CYP3A, and does not induce CYP1A2, CYP2B6, or CYP3A.1
In vitro studies indicate that DXd is not a substrate of UDP-glucuronosyltransferase (UGT).1
In vitro studies indicate that DXd is a substrate of OATP1B1, OATP1B3, multidrug and toxin extrusion (MATE)2-k, P-glycoprotein (P-gp), multidrug resistance associated protein (MRP)1, and breast cancer resistance protein (BCRP).1 DXd does not inhibit organic anion transporter (OAT)1, OAT3, organic cation transporter (OCT)1, OCT2, OATP1B3, MATE1, MATE2-K, P-gp, BCRP, or bile salt export pump (BSEP) transporters.1
Datopotamab deruxtecan-dlnk, a Trop-2-directed antibody conjugated with a topoisomerase inhibitor, is an antineoplastic agent.1 Datopotamab deruxtecan-dlnk is composed of a humanized anti-Trop-2 immune globulin G (IgG)1 monoclonal antibody (datopotamab) covalently linked to a topoisomerase I inhibitor (DXd, an exatecan derivative) via a tetrapeptide-based cleavable linker.1 Deruxtecan is composed of a protease-cleavable maleimide tetrapeptide linker and the topoisomerase inhibitor, DXd.1 Datopotamab is produced in Chinese hamster ovary cells by recombinant DNA technology; deruxtecan is produced by chemical synthesis.1 Datopotamab deruxtecan-dlnk binds to Trop-2 on cells, including tumor cells, undergoes internalization and intracellular linker cleavage.1 Upon release, DXd causes DNA damage and apoptotic cell death.1
Peak plasma concentrations of datopotamab deruxtecan-dlnk are dose proportional.1 DXd plasma protein binding is approximately 98%.1 Datopotamab deruxtecan-dlnk undergoes intracellular cleavage by lysosomal enzymes to release DXd.1 Datopotamab is expected to be metabolized into small peptides and amino acids via catabolic pathways.1 DXd is primarily metabolized by CYP3A4 in vitro.1 The datopotamab deruxtecan-dlnk median elimination half-life is 4.8 days; the DXd median elimination half-life is 5.5 days.1
The mean volume of distribution and clearance of datopotamab deruxtecan-dlnk increase with increasing body weight (36-156 kg).1 In patients with moderate hepatic impairment (total bilirubin >1.5-3 times ULN and any AST), datopotamab deruxtecan-dlnk pharmacokinetics are comparable to patients with normal hepatic function; however, average steady state DXd area under the curve (AUC) was 2.5-fold higher in patients with moderate hepatic impairment compared to patients with normal hepatic function.1 Age (26-86 years), race (Asian, White, or Black), sex, mild hepatic impairment (total bilirubin ≤ULN and AST >ULN or total bilirubin between 1-1.5 times the ULN and any AST) or Clcr 30-<90 mL/minute do not have clinically important effects on the pharmacokinetics of datopotamab deruxtecan-dlnk.1 The effect of severe hepatic impairment (total bilirubin >3 times ULN and any AST) or Clcr<30 mL/minute on datopotamab deruxtecan-dlnk or DXd pharmacokinetics is unknown.1
Additional Information
The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer's labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.
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.
Datopotamab deruxtecan-dlnk is obtained through specialty pharmacy distributors.5 Contact manufacturer or consult the datopotamab deruxtecan-dlnk website ([Web]) for specific availability information.5
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Parenteral | For injection, concentrate, for IV infusion | 100 mg | Datroway® | Daiichi Sankyo |
AHFS® Drug Information. © Copyright, 1959-2026, Selected Revisions September 10, 2026. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, MD 20814.
Only references cited for selected revisions after 1984 are available electronically.
1. Daiichi Sankyo, Inc. DATROWAY® (datopotamab deruxtecan-dlnk) for injection prescribing information. Basking Ridge, NJ; 2026 May.
2. Sands J, Ahn MJ, Lisberg A, et al. Datopotamab deruxtecan in advanced or metastatic non-small cell lung cancer with actionable genomic alterations: results from the phase II TROPION-Lung05 study. J Clin Oncol. 2025;43(10):1254-1265.
3. Ahn MJ, Tanaka K, Paz-Ares L, et al. Datopotamab deruxtecan versus docetaxel for previously treated advanced or metastatic non-small cell lung cancer: the randomized, open-label phase III TROPION-Lung01 study. J Clin Oncol. 2025;43(3):260-272.
4. Bardia A, Jhaveri K, Im SA, et al. Datopotamab deruxtecan versus chemotherapy in previously treated inoperable/metastatic hormone receptor-positive human epidermal growth factor receptor 2-negative breast cancer: primary results from TROPION-Breast01. J Clin Oncol. 2025;43(3):285-296.
5. Datroway Access and Support. Accessed 2 June 2026. http://www.datrowayhcp.com.
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102. Zhang YL, Yuan JQ, Wang KF, et al. The prevalence of EGFR mutation in patients with non-small cell lung cancer: a systematic review and meta-analysis. Oncotarget. 2016; 7:78985-78993.
103. Reuss JE, Ismaila N, Ahluwalia A, et al. Therapy for Stage IV non-small cell lung cancer with driver alterations: ASCO Living Guideline, Version 2026.3.1 J Clin Oncol. 2026, JCO-26-00843.
104. Sana Al Sukhun et al. Systemic Treatment of Patients With Metastatic Breast Cancer: ASCO Resource-Stratified Guideline. JCO Glob Oncol 10, e2300285(2024). DOI:10.1200/GO.23.00285