puxitatug samrotecan (AZD8205)

P1/2, N=370, Recruiting, AstraZeneca | Trial completion date: Mar 2027 --> Sep 2027 | Trial primary completion date: Mar 2027 --> Sep 2027

P2, N=28, Not yet recruiting, M.D. Anderson Cancer Center

P3, N=700, Recruiting, AstraZeneca | Not yet recruiting --> Recruiting

P3, N=700, Not yet recruiting, AstraZeneca

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.

P1/2, N=370, Recruiting, AstraZeneca | Trial completion date: Jun 2026 --> May 2027 | Trial primary completion date: Jun 2026 --> May 2027

P1/2, N=340, Recruiting, AstraZeneca | Trial completion date: Dec 2025 --> Jun 2026 | Trial primary completion date: Dec 2025 --> Jun 2026

The comprehensive nature of this work increases our confidence in the understanding of these processes. We hope this analytical approach can inform future development of bioconjugate drug candidates.

P1/2, N=340, Recruiting, AstraZeneca | N=248 --> 340 | Trial completion date: Jun 2025 --> Dec 2025 | Trial primary completion date: Jun 2025 --> Dec 2025

Spatial analysis revealed that ACC subtypes have distinct TMEs, with enrichment of ACC-I immune cells that are restricted to the stroma. B7-H4 is highly expressed in poor-prognosis ACC-I subtype and is a potential therapeutic target.

To further exploit the DNA damage elicited by the specific delivery of the TOP1i warhead, the combination of AZD8205 with a novel poly-ADP ribose polymerase 1 (PARP1) selective inhibitor, AZD5305, was investigated. These data demonstrate that AZD8205 is a promising therapeutic candidate for the treatment of B7-H4 positive solid tumors. A first in human phase I/IIa study in patients with advanced solid tumors is currently ongoing (NCT05123482).

Secondary objectives include assessing initial activity (objective response and progression-free survival by RECIST v1.1, and overall survival), pharmacodynamics, pharmacokinetics, and immunogenicity. The trial is currently recruiting and will enroll patients globally.