Positive FDA Type B Meeting Enables Development of Oz-V for Oropharyngeal Cancer

During a type B end-of-phase 2 meeting between BioAtla Inc and the FDA regarding a trial evaluating the conditionally active biologic antibody drug conjugate (CAB ADC) ozuriftamab vedotin (Oz-V) in treatment of human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC), the parties have settled on a phase 3 trial design with dosages and end points that support potential accelerated approval. The meeting allows for initiation of phase 3, with projected trial advancement in early 2026.¹

“The actionable regulatory alignment … enables initiation of the first [p]hase 3 study of a CAB ADC in an indication that represents a sizable and steadily growing population that is poorly served by current standard of care agents, including EGFR inhibitors,” said Jay M. Short, chief executive officer of BioAtla Inc, in a press release.

For full approval, the phase 3 trial will require randomization and stratification of approximately 300 patients with OPSCC between 2 open label treatment arms. Patients randomized to the experimental arm will receive 1.8 mg/kg of Oz-V every other week; patients in the control arm will receive either cetuximab (Erbitux), docetaxel, or methotrexate monotherapy. A statistically significant improvement of overall survival (OS) is needed for full approval, while an accelerated approval requires statistically significant improvement of confirmed overall response rate (ORR) by blinded independent central review (BICR) supported by an adequately characterized duration of response (DOR) without detriment in OS.

Data from phase 2 (NCT05271604) demonstrated improvement in overall response rate (ORR) and overall survival (OS), suggesting promising clinical performance. The ORR was found to be 45% (confirmed and unconfirmed); the median OS was 11.6 months, an increase compared with other studies testing monotherapies of either cetuximab, docetaxel, or methotrexate (ORR, 0%–3.4%; median OS, 4.4 months).

About Oz-V and the Unmet Need in OPSCC

Oropharyngeal squamous cell carcinoma is the sixth most common cancer worldwide, with 90% of HPV-positive cases attributed to HPV 16.² It can present with a persistent sore throat, lump in the neck, voice hoarseness, and unexplained weight loss, which can significantly reduce a patient’s quality of life.

While current targeted therapies such as EGFR inhibitors and other standard-of-care treatment regimens have demonstrated initial effectiveness in treatment and management of oral cancers, resistance mechanisms and treatment-related toxicities remain challenges.³

As a conditionally and reversibly active ADC, Oz-V targets ROR2 overexpression, which is associated with poor prognosis and chemo- and immunotherapy resistance.

“This underscores the potential of the CAB platform technology,” noted Short in the press release.

In July 2024, the FDA granted fast track designation to the agent in metastatic head and neck squamous cell carcinoma that progressed following treatment with platinum-based chemotherapy and a PD-(L)1 inhibitor.⁴

Given the increasing incidence of OPSCC, continued development of Oz-V treatment and is a pertinent step toward filling this therapeutic gap. Continued research in phase 3 and eventual publication of trial data will be essential to deepening understanding of Oz-V’s clinical benefits. Furthermore, a path to accelerated approval will be essential to earlier treatment and management of this serious condition.

REFERENCES:

1. Development Plan for Ozuriftamab Vedotin in Oropharyngeal Squamous Cell Carcinoma (OPSCC) Following Productive Type B (End of Phase 2) Meeting with FDA. News release. BioAtla, Inc. Published September 8, 2025. Accessed September 9, 2025.https://tinyurl.com/4bkkpweh

2. Jamal Z, Anjum F. Oropharyngeal Squamous Cell Carcinoma. National Institutes of Health; 2023. Accessed September 10, 2025. https://www.ncbi.nlm.nih.gov/books/NBK563268/

3. Veeraraghavan VP, Daniel S, Dasari AK, et al. Emerging targeted therapies in oral oncology: Focus on EGFR inhibition. Oral Oncol Rep. 2024;11:100592. doi:10.1016/j.oor.2024.1005923.

4. BioAtla granted FDA fast track designation for ozuriftamab vedotin (CAB-ROR2-ADC) for treatment of patients with recurrent or metastatic squamous cell carcinoma of the head and neck. News release. BioAtla, Inc. July 23, 2024. Accessed September 10, 2025. https://tinyurl.com/3kderfw6