92Bio, Inc. (www.92biotech.com), a clinical-stage biotechnology company developing next-generation T-cell engaging antibodies (TCEs), announced dosing of the first patient in a Phase 1 clinical trial evaluating NTB-928 for the treatment of platinum-resistant ovarian cancer. The trial is being conducted at multiple US sites, with the first patient dosed at START New York-Long Island under the direction of Principal Investigator Dr. Geraldine O'Sullivan Coyne, MD.

NTB-928 combines an affinity-tuned anti-CD3 moiety with an avidity-dependent FOLR1-binding arm for tumor versus normal selectivity. The dual-mechanism design enables potent killing of FOLR1-overexpressing ovarian cancer cells while sparing normal tissues that express trace FOLR1—a key limitation of conventional approaches targeting this antigen. Notably, FOLR1 is overexpressed in greater than 75% of ovarian cancer. Preclinical data supporting NTB-928's differentiated selectivity profile have been published in Oncoimmunology (Avanzino et al., 2022).

The ongoing Phase 1, single-arm, open-label trial utilizes a Bayesian Optimal Interval dose-escalation design with backfill (BOIN-BF) to evaluate the safety, tolerability, and preliminary activity of NTB-928.

"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 was purpose-built to solve the selectivity challenge that has constrained FOLR1 targeted T-cell engagers in ovarian cancer. Its unique combination of affinity-tuned CD3 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."

“The initiation of this study represents an important step forward in evaluating a novel approach for patients with platinum-resistant ovarian cancer, where significant unmet needs remain,” said Geraldine O'Sullivan Coyne, MD, Principal Investigator at START New York-Long Island who dosed the first patient. “We are proud to support the clinical development of NTB-928 and grateful for the strong collaboration between START, 92Bio, and Northwell Health Cancer Institute. Milestones like this are only possible through a shared commitment to advancing research and expanding opportunities for patients.”