Antibody-drug Conjugate Approved for Certain Patients With Advanced Triple-negative Breast Cancer
Datopotamab deruxtecan-dlnk was approved to treat PD-1/PD-L1 inhibitor-ineligible, advanced triple-negative breast cancer.
The U.S. Food and Drug Administration (FDA) approved datopotamab deruxtecan-dlnk (Dato-DXd; Datroway) for adults with unresectable or metastatic triple-negative breast cancer (TNBC) who are ineligible for PD-1/PD-L1 immune checkpoint inhibitor therapy.
Dato-DXd is an antibody-drug conjugate (ADC) in which a toxic topoisomerase I inhibitor (deruxtecan-dlnk) is joined with a Trop-2-targeting antibody (datopotamab). Trop-2 is preferentially expressed in many breast cancers, and upon binding to Trop-2 on the cellular surface, Dato-DXd enters the cell, where the topoisomerase I inhibitor component detaches and kills the cell. The development and characterization of Dato-DXd was first published in Molecular Cancer Therapeutics, a journal of the American Association for Cancer Research (AACR).
TNBC does not respond to breast cancer therapies that target hormone receptors and/or human epidermal growth factor 2 (HER2), so patients have typically been treated with first-line chemotherapy. Although immune checkpoint inhibition has expanded the first-line treatment options available to some patients with TNBC, most patients are ineligible due to the lack of PD-L1 expression on their TNBC tumors. For patients ineligible for immune checkpoint inhibitor therapy, Trop-2-targeting ADCs like Dato-DXd and sacituzumab govitecan-hziy (Trodelvy) provide targeted treatment options.
The approval was based on results from TROPION-Breast02, a multicenter, international, open-label, randomized phase III clinical trial, which enrolled 644 patients. The conditions for enrollment were a diagnosis of unresectable or metastatic TNBC that had not previously received therapy for unresectable or metastatic disease and ineligibility for PD-1/PD-L1 inhibitor therapy. Patients were randomly assigned 1:1 to receive either Dato-DXd or the investigator’s choice of chemotherapy: paclitaxel, nab-paclitaxel, capecitabine, eribulin, or carboplatin.
Patients in the Dato-DXd arm experienced significantly longer progression-free survival (PFS) with a median of 10.8 months compared with the patients in the chemotherapy arm, who experienced a median PFS of 5.6 months. Overall survival was also significantly better in the Dato-DXd arm, than in the chemotherapy arm (median 23.7 months vs. 18.7 months). Finally, the confirmed objective response rate was 64% in the Dato-DXd arm, compared with 30% in the chemotherapy arm.
The recommended dose of Dato-DXd is 6 mg/kg of body weight, up to a maximum of 540 mg in patients who weigh at least 90 kg, administered as an intravenous infusion once every three weeks until disease progression or unacceptable toxicity.
TNBC, which accounts for approximately 11% of breast cancers, is an aggressive subtype in which cells do not express hormone receptors for estrogen and progesterone and do not overexpress HER2. Without such targetable traits, TNBC cells do not respond to targeted therapies that are effective for hormone-receptor- and/or HER2-positive breast cancers. According to federal statistics, it was estimated that 321,910 individuals would be diagnosed with female breast cancer and 42,140 patients would die of the disease in the United States in 2026.
The FDA rendered its decision on May 22, 2026. Check this resource for updated information on all therapeutics regulated by the FDA.