felmetatug vedotin (PF-08046048)

P1, N=246, Terminated, Seagen, a wholly owned subsidiary of Pfizer | Trial completion date: Dec 2025 --> May 2025 | Active, not recruiting --> Terminated | Trial primary completion date: Dec 2025 --> May 2025; The trial was terminated for strategic reasons. The decision was not based on any safety and/or efficacy concerns

P1, N=236, Active, not recruiting, Seagen, a wholly owned subsidiary of Pfizer | N=572 --> 236 | Trial completion date: Nov 2027 --> Dec 2025 | Trial primary completion date: Nov 2027 --> Dec 2025

B7-H4-directed agents, particularly antibody-drug conjugates (ADCs) like puxitatug samrotecan (AZD8205), felmetatug vedotin (SGN-B7H4V), and GSK5733584, have demonstrated early clinical activity with promising response rates in triple-negative breast cancer (TNBC). Combination strategies, such as ADCs with anti-PD-1 or PARP inhibitor therapies, have also shown enhanced tumor regression in preclinical models and are the subject of several ongoing clinical trials. This review highlights the current landscape of B7-H4-targeted agents, their progress in clinical trials, and the potential for combination approaches to improve outcomes in B7-H4-expressing cancers.

P1, N=572, Active, not recruiting, Seagen Inc. | Recruiting --> Active, not recruiting

P1, N=572, Recruiting, Seagen Inc. | N=430 --> 572 | Trial completion date: Jan 2027 --> Nov 2027 | Trial primary completion date: Jun 2025 --> Nov 2027

P1, N=400, Recruiting, Seagen Inc. | Active, not recruiting --> Recruiting | N=164 --> 400

The immune checkpoint ligand B7-H4 is a promising molecular target expressed by multiple solid tumors. SGN-B7H4V demonstrates robust antitumor activity in preclinical models through multiple potential mechanisms. Altogether, these preclinical data support the evaluation of SGN-B7H4V as a monotherapy in the ongoing phase 1 study of SGN-B7H4V in advanced solid tumors (NCT05194072) and potential future clinical combinations with immunotherapies.

P1, N=164, Active, not recruiting, Seagen Inc. | Recruiting --> Active, not recruiting | N=400 --> 164

Responses were observed at all tested dose levels and across various tumor types. Dose expansion in select tumor types is planned.

This vedotin drug linker system has been clinically validated in multiple ADC programs, including brentuximab vedotin, enfortumab vedotin, and tisotumab vedotin. Moreover, SGN-B7H4V in combination with an anti-PD1 agent led to improved antitumor activity and elicited durable immune memory. Altogether, these nonclinical data further support the evaluation of SGN-B7H4V as a monotherapy in the ongoing Phase 1 Study of SGN-B7H4V in Advanced Solid Tumors ( NCT05194072 ) and potential future clinical combinations with immunotherapies.

DOR, PFS, and OS will be estimated using the Kaplan–Meier method. Enrollment for Part A is ongoing in North America and is planned in Europe.

This vedotin drug linker system has been clinically validated by multiple ADC programs, including brentuximab vedotin, enfortumab vedotin, tisotumab vedotin, and polatuzumab vedotin. Finally, SGN-B7H4V drove robust, curative activity in an immunocompetent tumor model as a monotherapy and paired well with an anti-PD1 agent. Altogether, these data support the evaluation of SGN-B7H4V as a monotherapy in a first-in-human phase 1 clinical study and potential future clinical combinations with immunotherapies.