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SAN ANTONIO -- The investigational agent datopotamab deruxtecan (Dato-DXd) offered antitumor activity with a manageable safety profile in patients with previously treated metastatic triple-negative breast cancer (TNBC), according to results of a phase I trial.

In updated data from a cohort in the , 15 of 44 patients responded to the agent, for a 34% objective response rate (ORR) per blinded independent central review, reported Ian Krop, MD, PhD, of the Susan F. Smith Center for Women's Cancers at the Dana Farber Cancer Institute in Boston.

After a median follow-up of 7.6 months, one additional response was awaiting confirmation and 17 other patients had stable disease, he stated in a presentation at the San Antonio Breast Cancer Symposium.

The median duration of response (DOR) was not reached, with the majority of responses ongoing at data cutoff.

"Despite recent advances in the treatment of TNBC, a significant need remains to improve patient outcomes, underscoring the importance of developing new and effective therapies," Krop said in a . "These preliminary results with datopotamab deruxtecan in pre-treated patients with metastatic TNBC are very encouraging and further evaluation of this agent is warranted."

Dato-DXd is an . The drug has a "humanized anti-TROP2 IgG13 monoclonal antibody [that is] attached to a topoisomerase I inhibitor payload, an exatecan derivative, via a tetrapeptide-based cleavable linker," according to developer AstraZeneca/Daiichi Sankyo.

The trial represents the first-in-human, open-label evaluation of Dato-DXd in patients with advanced solid tumors refractory to, or relapsed from standard treatment, or for whom no standard treatment is available, according to the developer. The drug doses in the trial were 6 mg/kg and 8 mg/kg.

Participants had metastatic TNBC with disease progression following standard treatment. They were treated with a median of three prior therapies, most commonly taxanes (91%), followed by platinum-based chemotherapy (52%), immunotherapy (43%), and topoisomerase I inhibitor-based ADCs (30%). At data cutoff, 30% of patients remained on treatment, according to the developer.

Krop's group also reported that, in a subgroup of 27 patients with measurable disease who were previously untreated with a topoisomerase I inhibitor-based ADC, the ORR was 52% with Dato-DXd: 13 responses with one additional response awaiting confirmation. Stable disease was seen in nine additional patients after a median follow-up of 8.8 months. A disease control rate of 81% was noted in this subgroup of patients.

Treatment-emergent adverse events (AEs) occurring in ≥15% of patients included nausea, stomatitis, vomiting, fatigue, alopecia, mucosal inflammation, constipation, headache, decreased lymphocyte count, decreased neutrophil count, pyrexia, anemia, pruritis, hypokalemia, diarrhea, and cough. Grade ≥3 treatment-related AEs were seen in 23%. There were no cases of .

Neelima Vidula, MD, of Mass General Cancer Center/Harvard Medical School in Boston, told 名媛直播 that ADCs "are really interesting because [they] can deliver a chemotherapy agent to a cancer cell, and there also can be a bystander effect induced by the agent itself, which means it kills other nearby cancer cells as well."

"This needs to be followed-up in phase III trials," Vidula added. "It will be interesting to follow development of this agent, and see where it fits in our treatment paradigm."

Based on "these encouraging results," a phase III study is planned, said Cristian Massacesi, MD, AstraZeneca chief medical officer and oncology chief development officer, in the press release.

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