Article
作者: Oaknin, Ana ; Boni, Valentina ; Zeng, Xing ; van Dongen, Marloes G J ; Lorusso, Domenica ; Provencher, Diane ; Baka, Sofia ; Lheureux, Stephanie ; Kaisermann, Morrys ; Jalkanen, Katriina ; Moreno, Victor ; Lee, Jung-Yun ; McKean, William ; Kowalyszyn, Ruben ; Malinowska, Izabela A ; Ürün, Yüksel ; Bedard, Philippe L ; Schutte, Tim ; Ray-Coquard, Isabelle ; Liu Burström, Lisa
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.