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

Sep 22, 2026

B7-H4 is overexpressed across multiple cancers, supporting its use as an immunotherapy target. This phase 1, open-label first-in-human study in advanced/metastatic breast, ovarian, and endometrial cancer assessed PF-07260437, a novel B7-H4×CD3 bispecific T-cell engager, focusing on safety, tolerability, and pharmacokinetics, with dose escalation every two weeks. Thirty female patients received subcutaneous escalating doses (100 μg start; with/without priming). Four patients (13.3%) had dose-limiting toxicities, including ALT/AST and bilirubin increases and cytokine release syndrome. No grade 4/5 TEAEs occurred, no objective responses were seen, and disease control rate was 33.3%. The sponsor terminated the study based on overall safety, with tolerable TEAEs and the MTD not reached.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages12

Reading Time30 min

AccessFree to download

Summary

Objectives and Study Design

Doses, Safety, and DLTs

Pharmacokinetics and Immunogenicity

Efficacy Outcomes

Trial Registration

Introduction

Rationale for CD3 Bispecific T-cell Engagers

Prior Approvals in Hematologic Malignancies

Emerging Evidence in Solid Tumors

Investigational New Drugs (2026) 44:305–316 [https://doi.org/10.1007/s10637-026-01614-2](https://doi.org/10.1007/s10637-026-01614-2) 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 Fengting Yan1 · Marcia Cruz‑Correa2 · Jennifer Specht3 · Edward Wenge Wang4 · Jinyu Lu5 · Hatem Soliman6 · Amy Jackson‑Fisher7 · Szu‑Yu Tang7 · Sibo Jiang7 · Christophe Le Corre7 · Meng Li8 · David Sommerhalder9 Received: 2 February 2026 / Accepted: 19 April 2026 / Published online: 22 May 2026 © The Author(s) 2026 Summary 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 treatmentrelated 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 * Fengting Yan [fengting.yan@swedish.org](fengting.yan@swedish.org); [yfengtin@fredhutch.org](yfengtin@fredhutch.org) 1 Swedish Cancer Institute, 1221 Madison Street, Seattle, WA 98104, USA 2 Pan American Center for Oncology Trials, 150 Av. Centro Médico, San Juan, PR 00935, USA 3 Fred Hutchinson Cancer Center, 1100 Fairview Ave N, Seattle, WA 98109, USA 4 City of Hope Comprehensive Cancer Center, 1500 E Duarte Rd, Duarte, CA 91010, USA 5 Montefiore Einstein Comprehensive Cancer Center, 1695 Eastchester Rd, Bronx, NY 10461, USA 6 Moffitt Cancer Center, 12902 USF Magnolia Drive, Tampa, FL 33612, USA 7 Pfizer, Torrey Heights, 11202 El Camino Real, San Diego, CA 92130, USA 8 Pfizer, 181 Oyster Point Blvd, South San Francisco, CA 94080, USA 9 NEXT Oncology, 2829 Babcock Rd Suite 300, San Antonio, TX 78229, USA Highlights • This study evaluated the safety, PK, immunogenicity, and anti-tumour activity of PF-07260437 in patients with solid tumours • Overall, 6 treatment-related DLTs were reported in 4 patients, which eventually resolved • DCR across cohorts was 33.3%(10/30) • PF-07260437 was tolerable in patients with breast, ovarian, and endometrial cancers with a manageable safety profile Keywords B7-H4 · Bispecific · T-cell engager · First-in-human trial · Solid tumours Introduction CD3 bispecific T-cell engagers are designed to simultaneously bind to specific tumour-expressed antigens on cancer cells and T cell activatio

FAQs

What was the main purpose of the PF-07260437 phase 1 study?

The study evaluated safety, pharmacokinetics, and preliminary anti-tumour activity of PF-07260437 in patients with advanced or metastatic breast, ovarian, and endometrial cancer. Primary objectives included determining MTD/RDE and safety and tolerability.

How was PF-07260437 administered and what dose escalation approach was used?

Patients received escalating doses of PF-07260437 subcutaneously every two weeks, starting at 100 μg, with some cohorts using a priming dose. A Bayesian logistic regression model (BLRM) guided dose escalation.

What were the key safety and efficacy findings?

Four patients (13.3%) experienced DLTs, including elevated liver enzymes/bilirubin and cytokine release syndrome, with no grade 4/5 TEAEs and no TEAEs causing discontinuation. No objective responses were observed; disease control rate was 33.3% (95% CI 17.3%, 52.8%).

Was the maximum tolerated dose reached and how did cytokines change?

The maximum tolerated dose (MTD) was not reached. Exposures at PF-07260437 ≥ 300 μg aligned with theoretic efficacious ranges, with a transient increase in serum cytokines after the first dose.

Sep 22, 2026

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