First-line dual targeting combination shows encouraging, durable responses in triple-negative breast cancer

Encouraging antitumour efficacy was shown with pumitamig, an investigational bispecific antibody targeting PD-L1 and VEGF-A, in combination with the TROP2 antibody drug conjugate (ADC) DB-1305/BNT325 in 30 patients with advanced or metastatic triple-negative breast cancer (TNBC), as recently reported at the ESMO Breast Cancer 2026 congress (Abstract 426RO). Despite the small patient population, “every patient had some kind of reduction in their tumour size,” noted Prof. Rebecca A. Dent, of National Cancer Centre Singapore (NCCS), commenting the results from the phase II expansion cohort of a multicenter, open-label phase I/II trial investigating the combination as first-line treatment. In the study, disease control rate (DCR) was 96.7% (95% CI: 56.5, 89.7) (Figure). “For me, this is quite impactful”, she added.

At data cut-off, 66.7% of patients remained on treatment, and median treatment duration was 6.9 months. At a median follow-up of 7.7 months, unconfirmed objective response rate (ORR) was 83.3 (95% CI: 65.3, 94.4) and confirmed ORR was 76.7% (95% CI: 57.7, 90.1). Responses were durable, with 95.2% ongoing responses at 6 months. According to Dent, durability of responses has a strong biological rationale based on the synergistic effect of the dual targeting of pumitamig and the TROP1-directed ADC, which may influence the tumour microenvironment. “There is a lot of interest in bispecific antibodies, and we have learned from our colleagues in liver cancer how potentially important it is to target VEGF in combination with targeting the immune system. The result is not just additive, it is potentially synergistic,” she highlighted. “This is a highly active combination. I think this study data provide proof of concept that combining ADCs with bispecific antibodies can affect the tumour microenvironment.”

Pumitamig plus BNT325 was well tolerated and had a manageable safety profile. Stomatitis was commonly observed, being grade 1-2 in most cases, and adverse events were managed by dose reductions and/or interruptions. More than 15% of patients reported grade 3-4 treatment-related adverse events (TRAEs). “It will be interesting to understand whether they resolve quickly with dose reductions, as it does seem to be the case,” she said, noting that larger phase III trials further evaluating safety are needed. “However it is very reassuring that interstitial lung disease was not reported.”