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•स्क्रिनमा देखिने चुरोट: सुर्तीजन्य हानि न्यूनीकरण नीतिमा दक्षिण एसियाले अझै के छुटाइरहेको छ•नेपालमा पिसाब नलीको संक्रमण र एन्टिबायोटिक प्रतिरोधको बढ्दो संकट•Frontline Perspectives on Nursing Leadership in Nepal•Protecting the Smallest Lungs from the Hidden Grip of RSV in Kathmandu•The Heavy Burden of Bullying on Student Wellbeing in Nepal•The Emerging Landscape of Thyroid Health in Central Nepal•How a Recent Western Nepal Study is Redefining Anemia Diagnosis•How H. Pylori is Impacting the Health of Karnali’s High-Altitude Communities•Sweet Poison, Bitter Reality: The Unseen Diabetes Epidemic Among Nepal’s Youth•How Missing Checklists and Protocols are Costing Lives in Nepal’s ERs•स्क्रिनमा देखिने चुरोट: सुर्तीजन्य हानि न्यूनीकरण नीतिमा दक्षिण एसियाले अझै के छुटाइरहेको छ•नेपालमा पिसाब नलीको संक्रमण र एन्टिबायोटिक प्रतिरोधको बढ्दो संकट•Frontline Perspectives on Nursing Leadership in Nepal•Protecting the Smallest Lungs from the Hidden Grip of RSV in Kathmandu•The Heavy Burden of Bullying on Student Wellbeing in Nepal•The Emerging Landscape of Thyroid Health in Central Nepal•How a Recent Western Nepal Study is Redefining Anemia Diagnosis•How H. Pylori is Impacting the Health of Karnali’s High-Altitude Communities•Sweet Poison, Bitter Reality: The Unseen Diabetes Epidemic Among Nepal’s Youth•How Missing Checklists and Protocols are Costing Lives in Nepal’s ERs

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.

Researchers

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

Abstract

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. 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. Mocertatug rezetecan monotherapy or combination therapy has a manageable safety profile and clinically meaningful anti-tumor activity in gynecological cancers. 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). 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). 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. BEHOLD-1: approximately 675 patients. BEHOLD-2: approximately 305 patients. BEHOLD-1: September 2027. BEHOLD-2: June 2027. BEHOLD-1: NCT06431594. BEHOLD-2: NCT06796907.
Source: PubMed (PMID: 42850140)View Original on PubMed