A phase 1 study of PF-07260437, a B7-H4 × CD3 bispecific T-cell engager, in patients with advanced or metastatic breast, ovarian, and endometrial cancer

B7-H4 is overexpressed in various cancers, making it a promising target for cancer immunotherapy. This phase 1, open-label, first-in-human study in patients with advanced/metastatic breast, ovarian and endometrial cancer evaluates the safety, pharmacokinetics (PK), and anti-tumour activity of PF-07260437, a novel B7-H4xCD3 bispecific T-cell engager. Enrolled patients received escalating doses of PF-07260437 (with/without priming dose) subcutaneously every two weeks, with a starting dose of 100 µg. Primary objectives included determination of maximum tolerated dose (MTD)/recommended dose for expansion (RDE), safety and tolerability. Secondary objectives included PK parameters and immunogenicity. Bayesian logistic regression model (BLRM) was used to guide dose escalation. Thirty patients with advanced/metastatic breast, ovarian and endometrial cancer received the study treatment during dose escalation; all were female (median age, 61.0 [41-75] years). Four patients (13.3%) experienced DLTs (alanine aminotransferase increased, aspartate aminotransferase increased, blood bilirubin increased, cytokine release syndrome). Overall, 29 (96.7%) patients experienced 202 treatment-related TEAEs (no grade 4/5 TEAEs); no TEAE resulted in study discontinuation. No objective response was observed. Disease control rate (DCR) was 33.3% (95% CI: 17.3%, 52.8%). PF-07260437 ≥ 300 μg resulted in exposures in the theoretic efficacious range, with a transient increase in serum cytokines levels following the first dose. The study was terminated by the Sponsor based on the overall assessment of the observed clinical safety, preliminary efficacy, pharmacokinetic and pharmacodynamic data. The MTD was not reached. PF-07260437 was tolerable in patients with breast, ovarian, and endometrial cancers with manageable TEAEs. TRIAL REGISTRATION NUMBER: NCT05067972. REGISTRATION DATE: 5 October, 2021.