Dr Monk on the Investigation of B7-H4–Directed Vedotin ADCs in Gynecologic Cancers

Bradley Monk, MD, FACS, FACOG, professor, the Division of Gynecologic Oncology, University of Arizona College of Medicine and Creighton University School of Medicine; director, principal investigator, Community Research Development, HonorHealth Research Institute, vice president, member, the Board of Directors, the GOG-Foundation; co-director, GOG-Partners, discusses the rationale for investigating B7-H4–directed vedotin antibody-drug conjugates (ADCs) and highlights how these agents may address unmet needs for patients with gynecologic cancers.

The ongoing, phase 1 SGNB7H4V-001 trial (NCT05194072) is investigating the efficacy of the B7-H4–directed vedotin, SGN-B7H4V in patients with advanced solid tumors, Monk begins. Vedotin ADCs such as tisotumab vedotin-tftv (Tivdak) have previously demonstrated efficacy in patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy, Monk notes.

Preliminary findings from the trial, which were presented at the 2023 ESMO Congress, highlighted the promising activity of SGN-B7H4V in diverse cancer types, Monk states. The trial evaluated different dosing schedules, comparing administration on days 1 and 8 of a 21-day cycle with administration of the agent on days 1 and 15 of 28-day cycles, he details. Initial data suggest robust activity and support the safety profile observed with both dosing schedules, he says.

Among 28 patients with breast cancer, 7 achieved objective responses, while 4 out of 20 patients with ovarian cancer responded to the treatment. Notably, a complete response was observed in 1 of 16 patients with endometrial cancer, and the drug had activity in lung and biliary tract cancers. The responses were characterized as early, deep, and durable.

Adverse effects associated with SGN-B7H4V were comparable to that of other vedotin ADCs, Monk continues. Fatigue, neuropathy, and bone marrow suppression were all common, while diarrhea levels remained low. Notably, alopecia and pneumonitis were rare occurrences, Monk notes.

These results contribute valuable toward the development of targeted therapies for various solid tumors, exemplified by the early and durable responses seen with SGN-B7H4V, Monk says. The findings also support ongoing efforts to advance the understanding of ADCs and their potential in treating patients with advanced solid tumors, he adds. Furthermore, the study's exploration of dosing schedules offers information for optimizing the administration of SGN-B7H4V, Monk emphasizes. The every-other-week schedule emerged as a preferred choice based on its demonstrated efficacy and safety. Further research may pave the way for the continued development and potential clinical application of SGN-B7H4V in the treatment landscape of advanced solid tumors, Monk concludes.