BEHOLD-1 and -2: phase 1/2 randomized studies evaluating the B7 homolog 4 protein-targeted antibody-drug conjugate mocertatug rezetecan in patients with solid tumors, including endometrial and ovarian cancers.

BACKGROUND

B7 homolog 4 protein (B7-H4) is an immunoregulatory protein that is overexpressed in gynecological cancers and has limited expression in normal tissues. Mocertatug rezetecan (Mo-Rez; GSK5733584) is a novel antibody-drug conjugate comprising an anti-B7-H4 antibody conjugated to a topoisomerase 1 inhibitor payload via a protease-cleavable linker and has shown early clinical activity in gynecological cancers.

PRIMARY

OBJECTIVE

The BEHOLD program is evaluating the safety, tolerability, and preliminary anti-tumor activity of mocertatug rezetecan as monotherapy (BEHOLD-1) and as combination therapy (BEHOLD-2) in gynecological cancers.

STUDY HYPOTHESIS: Mocertatug rezetecan monotherapy or combination therapy has a manageable safety profile and clinically meaningful anti-tumor activity in gynecological cancers.

TRIAL

DESIGN

BEHOLD-1 is a phase 1a/b study evaluating doses of intravenous mocertatug rezetecan in advanced solid tumors (phase 1a: dose escalation; phase 1b: randomized dose optimization/expansion). The phase 1/2 BEHOLD-2 study evaluates doses of intravenous mocertatug rezetecan with intravenous dostarlimab in endometrial cancer or with intravenous bevacizumab in ovarian cancer (part A: dose exploration; part B: dose expansion).

MAJOR INCLUSION/EXCLUSION CRITERIA: Eligible patients are defined as follows: BEHOLD-1 phase 1a: patients with advanced solid tumors; BEHOLD-1 phase 1b: patients with platinum-resistant ovarian cancer or advanced or recurrent endometrial cancer; BEHOLD-2 part A: patients with advanced or recurrent endometrial cancer or advanced ovarian cancer; BEHOLD-2 part B: patients with second-line-or-later mismatch repair proficient or microsatellite stable endometrial cancer or second-line-or-later platinum-sensitive ovarian cancer. For both studies, patients must have measurable disease per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1).

PRIMARY ENDPOINTS: BEHOLD-1 phase 1a: dose-limiting toxicities. BEHOLD-1 phase 1b: confirmed objective response rate per RECIST v1.1. BEHOLD-2 part A: dose-limiting toxicities and safety. BEHOLD-2 part B: confirmed objective response rate per RECIST v1.1.

SAMPLE SIZE: BEHOLD-1: approximately 675 patients. BEHOLD-2: approximately 305 patients.

ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING

RESULTS

BEHOLD-1: September 2027. BEHOLD-2: June 2027.

TRIAL REGISTRATION: BEHOLD-1: NCT06431594. BEHOLD-2: NCT06796907.