On May 22, the U.S. Food and Drug Administration (FDA) approved datopotamab deruxtecan-dlnk (Datroway), an antibody-drug conjugate targeting trophoblast cell surface antigen 2 (TROP2), for adult patients with unresectable or metastatic triple-negative breast cancer (TNBC) who are not candidates for PD-1/PD-L1 inhibitor therapy.
TROPION-Breast02
Efficacy was evaluated in TROPION-Breast02 (ClinicalTrials.gov identifier NCT05374512), a multicenter, open-label, randomized trial of 644 patients with unresectable or metastatic TNBC who had not received prior chemotherapy or other systemic anticancer therapy for unresectable or metastatic breast cancer and who were not candidates for PD-1/PD-L1 inhibitor therapy. Patients were excluded for a history of interstitial lung disease (ILD)/pneumonitis requiring treatment with steroids, ongoing ILD/pneumonitis, or clinically significant corneal disease at screening.
Random assignment was stratified by geographic region (United States, Canada, and Europe, or rest of world), PD-L1 status (positive or negative), and disease-free interval history (de novo or ≤ 12 months or > 12 months). Patients were randomly assigned 1:1 to receive either datopotamab deruxtecan-dlnk (n = 323) or investigator’s choice of chemotherapy (n = 321)—either paclitaxel (28%), nab-paclitaxel (54%), capecitabine (2.2%), eribulin (11%), or carboplatin (4.7%).
The major efficacy outcome measures were progression-free survival as assessed by blinded independent central review based on Response Evaluation Criteria in Solid Tumors version 1.1 and overall survival; additional efficacy outcome measures included confirmed overall response rate by blinded independent central review.
Median progression-free survival was 10.8 months (95% confidence interval [CI] = 8.6–13.0 months) in the datopotamab deruxtecan-dlnk arm and 5.6 months (95% CI = 5.0–7.0 months) in the chemotherapy arm (hazard ratio [HR] = 0.57, 95% CI = 0.47–0.69, P < .0001). Median overall survival was 23.7 months (95% CI = 19.8–25.6 months) and 18.7 months (95% CI = 16.0–21.8 months) in the respective arms (HR = 0.79, 95% CI = 0.64–0.98, P = .0290). Confirmed overall response rate was 64% (95% CI = 58%–69%) and 30% (95% CI = 25%–36%) in the respective arms.
Recommended Dosage
The recommended datopotamab deruxtecan-dlnk dose is 6 mg/kg (up to a maximum of 540 mg for patients weighing ≥ 90 kg) administered as an intravenous infusion once every 3 weeks (21-day cycle) until disease progression of unacceptable toxicity.
The prescribing information includes warnings and precautions for ILD and pneumonitis, ocular adverse reactions, stomatitis/oral mucositis, and embryo-fetal toxicity.
This review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence which provides a framework for concurrent submission and review of oncology drugs among international partners. For this review, the FDA collaborated with the Australian Therapeutic Goods Administration, the Brazilian Health Regulatory Agency (ANVISA), Health Canada, Singapore’s Health Sciences Authority, and Switzerland’s Swissmedic. The applications may still be under review at the other regulatory agencies.
This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.
This application was granted Priority Review.
