92Bio Doses First Patient in Phase 1 Trial of NTB-928, a Next-Generation Bispecific T-Cell Engager for Platinum-Resistant Ovarian Cancer
核心洞察
92Bio has dosed the first patient in a Phase 1 clinical trial of NTB-928 (搜索), a bispecific T-cell engager targeting FOLR1 (搜索) and CD3 (搜索), for platinum-resistant ovarian cancer (搜索).
NTB-928 (搜索) employs a dual-mechanism design combining affinity-tuned CD3 (搜索) engagement with avidity-dependent FOLR1 (搜索) binding to selectively kill tumor cells while sparing normal tissues.
FOLR1 (搜索) is overexpressed in more than 75% of ovarian cancers, and the selectivity challenge has historically constrained FOLR1-targeted T-cell engagers in this indication.
92Bio, Inc. (搜索), a clinical-stage biotechnology company based in Hayward, California, announced today that the first patient has been dosed in a Phase 1 clinical trial evaluating NTB-928 (搜索) for the treatment of platinum-resistant ovarian cancer (搜索). The milestone marks the company's transition into the clinical development stage for its lead bispecific T-cell engager (TCE) candidate.
The first patient was dosed at START New York-Long Island (搜索) under the direction of Principal Investigator Dr. Geraldine O'Sullivan Coyne, MD. The trial is being conducted across multiple US sites.
A Differentiated Approach to FOLR1 (搜索) Targeting
NTB-928 (搜索) is a fully human bispecific T-cell engaging antibody that targets both FOLR1 (搜索) and CD3 (搜索). Its selectivity derives from two synergistic design features: an affinity-tuned anti-CD3 arm that drives potent anti-tumor T-cell activation with reduced cytokine secretion, and a bivalent FOLR1-binding arm that confers avidity-dependent binding to tumor cells overexpressing FOLR1 while sparing normal cells that express only trace levels of the antigen.
Neither feature alone is sufficient for selectivity; both are required. This dual-mechanism design addresses what has been a key limitation of conventional approaches targeting FOLR1 (搜索) — the risk of on-target, off-tumor toxicity against normal tissues that express low levels of the antigen.
FOLR1 (搜索) is overexpressed in greater than 75% of ovarian cancers, making it a compelling therapeutic target. Preclinical data supporting NTB-928 (搜索)'s differentiated selectivity profile were published in Oncoimmunology (Avanzino et al., 2022), demonstrating robust tumor clearance in vitro, ex vivo, and in vivo with a favorable safety profile.
Trial Design and Objectives
The ongoing Phase 1 study is a single-arm, open-label trial utilizing a Bayesian Optimal Interval dose-escalation design with backfill (BOIN-BF). The primary objectives are to evaluate the safety, tolerability, and preliminary activity of NTB-928 (搜索) in patients with platinum-resistant ovarian cancer (搜索).
Leadership Perspectives
"Dosing the first patient in this study is a defining moment for 92Bio," said Ben Buelow, MD, PhD, Chief Executive Officer of 92Bio. "NTB-928 (搜索) was purpose-built to solve the selectivity challenge that has constrained FOLR1 (搜索) targeted T-cell engagers in ovarian cancer. Its unique combination of affinity-tuned CD3 (搜索) engagement and avidity-dependent FOLR1 binding positions it specifically as a best-in-class candidate for patients with ovarian cancer, and generally for FOLR1-positive malignancies beyond that."
Dr. Geraldine O'Sullivan Coyne, Principal Investigator at START New York-Long Island (搜索), emphasized the clinical significance: "The initiation of this study represents an important step forward in evaluating a novel approach for patients with platinum-resistant ovarian cancer (搜索), where significant unmet needs remain. We are proud to support the clinical development of NTB-928 (搜索) and grateful for the strong collaboration between START, 92Bio, and Northwell Health Cancer Institute (搜索). Milestones like this are only possible through a shared commitment to advancing research and expanding opportunities for patients."
About 92Bio
92Bio, Inc. (搜索) is a clinical-stage biotechnology company focused on developing differentiated T-cell engaging antibodies for the treatment of hematologic and solid tumors. The company's proprietary platform enables the engineering of bispecific antibodies with tumor-selective binding profiles designed to maximize efficacy while minimizing on-target, off-tumor toxicity.