92Bio Doses First Patient in Phase 1 Trial of NTB-928, a FOLR1×CD3 Bispecific T-Cell Engager Engineered for Tumor Selectivity in Platinum-Resistant Ovarian Cancer

92Bio, Inc. announced today the dosing of the first patient in a phase 1 clinical trial of NTB-928, a fully human bispecific T-cell engaging antibody (TCE) targeting folate receptor alpha (FOLR1) and CD3, in patients with platinum-resistant ovarian cancer (PROC).¹ The first patient was dosed at START New York-Long Island in collaboration with Northwell Health Cancer Institute, under the direction of principal investigator Geraldine O'Sullivan Coyne, MD.¹ The trial marks a clinical entry point for a mechanistically differentiated approach to FOLR1-directed immunotherapy — a target that has attracted significant drug development attention in ovarian cancer but has historically been constrained by on-target, off-tumor toxicity.

What is NTB-928 and how does it work?

NTB-928 is a fully human bispecific antibody engineered to redirect cytotoxic T cells toward FOLR1-overexpressing ovarian cancer cells. FOLR1 is expressed at high levels in more than 75% of ovarian cancers, making it an attractive tumor-associated antigen.¹ However, FOLR1 is also expressed at low levels in certain normal tissues — including lung epithelium and kidney proximal tubules — which has historically created an on-target, off-tumor toxicity challenge for therapies directed at this antigen.

NTB-928 addresses this through a dual-mechanism selectivity design.¹ The molecule combines an affinity-tuned anti-CD3 arm — calibrated to drive potent T-cell activation while reducing systemic cytokine release relative to higher-affinity CD3 binders — with a bivalent, avidity-dependent FOLR1-binding arm. The bivalent FOLR1 arm preferentially engages cells that overexpress FOLR1, exploiting the avidity effect: tumor cells densely expressing FOLR1 are bound and killed efficiently, while normal cells expressing only trace levels of FOLR1 are largely spared. Critically, neither feature alone is sufficient for selectivity; both are required in combination. Preclinical data supporting this differentiated selectivity profile have been published in Oncoimmunology.²

Why is platinum-resistant ovarian cancer such a difficult setting?

Platinum-resistant ovarian cancer, defined as disease that recurs within six months of prior platinum-based chemotherapy, represents one of the most difficult-to-treat settings in gynecologic oncology. Response rates to standard salvage chemotherapy regimens are typically below 20%, and overall survival remains poor.³ The clinical need has driven a wave of targeted and immunotherapeutic drug development in this setting, including ADC-based strategies — notably mirvetuximab soravtansine (Elahere), a FOLR1-targeting ADC that became the first biomarker-selected therapy approved for PROC in 2022.⁴

The FOLR1 antigen targeted by NTB-928 is the same target exploited by Elahere, but the mechanism is fundamentally different: rather than delivering a cytotoxic payload, NTB-928 redirects the patient's own T cells to recognize and destroy FOLR1-expressing tumor cells. A recent BioPharm International report on GSK's B7-H4 ADC highlights the continued investment in gynecologic oncology biologics targeting antigens with high tumor and low normal-tissue expression — a principle that underpins NTB-928's design.

The selectivity challenge NTB-928 is designed to solve reflects a broader engineering imperative the field is actively responding to. As Sabeen Mekan, MD, of Zymeworks told BioPharm International at BIO 2026, "I think the biggest innovation moving forward is on the payload side... bispecific, trispecific, and multispecific formats are designed to improve targeting precision and enhance therapeutic activity by engaging multiple epitopes or biological mechanisms simultaneously."

Meanwhile, CTIM-76, a CLDN6×CD3 bispecific TCE from Context Therapeutics in PROC, achieved a 29% confirmed overall response rate with low rates of cytokine release syndrome in phase 1, providing early validation that TCEs can generate meaningful clinical activity in ovarian cancer.

What are the phase 1 trial design and endpoints?

The ongoing phase 1 trial is a single-arm, open-label, multicenter dose-escalation study using a Bayesian Optimal Interval with backfill design to efficiently identify the recommended phase 2 dose while allowing additional patients to enroll at previously cleared dose levels.¹ Primary endpoints include safety and tolerability; secondary endpoints include preliminary anti-tumor activity.¹

"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."¹

"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," added O'Sullivan Coyne. "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."¹

References

1. 92Bio, Inc. Doses First Patient in Phase 1 Clinical Trial of NTB-928 in Platinum-Resistant Ovarian Cancer. (2016 Jul 1). Business Wire. https://www.businesswire.com/news/home/20260701011885/en/92Bio-Inc.-Doses-First-Patient-in-Phase-1-Clinical-Trial-of-NTB-928-in-Platinum-Resistant-Ovarian-Cancer
2. Avanzino BC, Prabhakar K, Dalvi P, Hartstein S, Kehm H, Balasubramani A, Boudreau AA, Buelow B, et al. (2022 Aug 20). T-cell engaging bispecific antibody with a tumor-selective bivalent folate receptor alpha binding arm for the treatment of ovarian cancer. Oncoimmunology. https://pubmed.ncbi.nlm.nih.gov/36016696/
3. Pujade-Lauraine E, Hilpert F, Weber B, et al. (2014 May 1). Bevacizumab combined with chemotherapy for platinum-resistant recurrent ovarian cancer: The AURELIA open-label randomized Phase III trial. J Clin Oncol. https://pubmed.ncbi.nlm.nih.gov/24637997/
4. FDA grants accelerated approval to mirvetuximab soravtansine-gynx for FRα positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer. (2022 Nov 14). US Food and Drug Administration. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-mirvetuximab-soravtansine-gynx-fra-positive-platinum-resistant