Dr Tarantino on the Potential Significance of SGN-B7H4V in Breast Cancer

Paolo Tarantino, MD, researcher, the European Institute of Oncology, clinical research fellow, Dana-Farber Cancer Institute, discusses ongoing investigations into the use of antibody-drug conjugates (ADCs) targeting B7-H4 vedotin, highlighting their potential significance for the treatment paradigm in breast cancer.

HER2 and TROP-2 have been the focus of research with ADCs in breast cancer, but novel targets are also under evaluation, Tarantino begins. B7-H4 is an interesting target for ADC development, Tarantino states. It serves as an immune checkpoint ligand with low expression in normal tissues but upregulated levels in various solid tumors, including breast cancer, he explains.

The phase 1 SGNB7H4V-001 trial (NCT05194072) is currently evaluating the B7-H4 vedotin SGN-B7H4V in patients with advanced solid tumors, Tarantino introduces. The ADC consists of a monoclonal antibody targeting B7-H4, linked to monomethyl auristatin E through a protease-cleavable linker, which is a similar design to that of ADCs like enfortumab vedotin-ejfv (Padcev) and tisotumab vedotin-tftv (Tivdak), Tarantino notes. In the phase 1 trial, 86 patients were enrolled in 2 cohorts exploring different dosing schedules, he details.

Early findings from this trial were presented at the 2023 ESMO Congress, where common adverse effects (AEs) were noted, including fatigue, peripheral sensory neuropathy, and cytopenia. These AEs aligned with the toxicity profile of other vedotin ADCs, Tarantino adds. Notably, the cohort with a 3-week dosing interval exhibited greater toxicity, and 2 patients experienced grade 5 toxicities. This resulted in the transition to a 4-week dosing schedule for all patients, Tarantino says.

Despite challenges, SGN-B7H4V demonstrated promising activity across various tumor types, Tarantino reports. Although predominantly studied in ovarian cancer, hormone receptor–positive breast cancer, and triple-negative breast cancer (TNBC), positive responses were observed with the agent in diverse cancers, Tarantino states. These included advanced breast cancer, ovarian cancer, endometrial cancer, lung cancer, and biliary tract cancers. Moreover, objective responses were observed in 7 of 28 patients with advanced breast cancer and 4 out of 20 patients with advanced ovarian cancer.

Although more data are awaited to confirm the agent's efficacy, initial results indicate the potential of SGN-B7H4V as an effective treatment across a spectrum of cancers, Tarantino emphasizes. Further study outcomes and other research will shed light on the future implications and clinical utility of this novel ADC, he concludes.