medwireNews: TROPION-PanTumor01 trial findings suggest that the TROP2-directed antibody–drug conjugate datopotamab deruxtecan (Dato-DXd) might offer a novel treatment option for patients with advanced triple-negative breast cancer (TNBC).
Presenting the initial TNBC cohort results of the phase 1 basket study at the ESMO Breast Cancer Virtual Congress 2021, Aditya Bardia (Massachusetts General Hospital Cancer Center, Boston, USA) said that Dato-DXd has a “manageable safety profile” and that the “emerging efficacy results show antitumor activity in heavily pretreated patients with metastatic TNBC.”
Dato-DXd – an anti-TROP2 immunoglobulin G antibody combined with a topoisomerase I inhibitor and a cleavable linker – has previously shown activity in the study’s cohort of relapsed and refractory non-small-cell lung cancer patients.
The current TNBC cohort had 24 patients unselected for TROP2 expression who had previously been given a median of four systemic treatments, with 88% receiving at least two. These included taxanes (83%), platinum-based chemotherapy (50%), and immunotherapy (33%), as well as sacituzumab govitecan (8%) or a PARP inhibitor (4%).
Dato-DXd was given intravenously every 3 weeks at a dose of 6 mg/kg (n=22) or 8 mg/kg (n=2), and at data cutoff 75% of patients were continuing treatment, while 25% of patients had discontinued following disease progression.
All participants experienced at least one treatment-related adverse event (TRAE), and grade 3 and more severe TRAEs occurred in 17% of the cohort. There were no serious or fatal TRAEs and none of the patients discontinued treatment because of AEs, but 25% of patients required a dose reduction, most commonly for stomatitis (13%) and mucosal inflammation (8%).
The majority of treatment-emergent AEs were nonhematologic grade 1 or 2 side effects; the most common any-grade events were stomatitis (63%), nausea (63%), fatigue (42%), vomiting (42%), alopecia (25%), cough (21%), and pruritus (21%), while anemia, headache, and constipation were each experienced by 17% of patients.
Bardia highlighted that there were no reports of drug-related interstitial lung disease, or grade 3 or more severe episodes of diarrhea or neutropenia.
Turning to efficacy results, the presenter said Dato-DXd had “impressive antitumor activity,” citing an objective response rate of 43% for the 21 patients assessed by blinded independent central review. These included a confirmed complete or partial response in 24% of patients and responses pending confirmation in 19%.
Just one patient experienced disease progression, giving a disease control rate of 95%. Thus, the majority of patients had a decrease in tumor volume and the majority of these responses occurred within the first 2 months of treatment, Bardia commented.
The investigator concluded that “further study in breast cancer is needed,” adding that “the hormone receptor-positive cohort is now enrolling.”
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