FDA Provides Guidance on Registrational Path for Ozuriftamab Vedotin in Oropharyngeal Squamous Cell Carcinoma

Following the completion of a Type B (end of phase 2) meeting, the FDA has aligned with BioAtla on the design of a potential phase 3 trial, including dosing regimen and end points, that may support the accelerated approval of its conditionally active biologic ROR2-targeted antibody-drug conjugate (ADC), ozuriftamab vedotin (BA3021; Oz-V), in oropharyngeal squamous cell carcinoma (OPSCC).1

Oz-V is a conditionally and reversibly active ADC specifically directed against ROR2, a transmembrane TKI receptor expressed across solid tumors, including head and neck cancer. Overexpression of ROR2 is driven by E6/E7 oncoproteins, which are associated with human papillomavirus (HPV) infection. This overexpression is linked to poor prognosis and resistance to both chemo- and immunotherapies.

Notably, the FDA granted fast track designation to Oz-V for the treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) who have previously experienced progression on a PD-1/L1 inhibitor and platinum-based chemotherapy.2

“The actionable regulatory alignment represents an important milestone for BioAtla as it enables initiation of the first phase 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,” Jay M. Short, PhD, chairman, chief executive officer and co-founder of BioAtla, Inc, stated in a news release.1 “Having a clear registrational path with the potential for accelerated approval is very positive for our near-term strategic partnering objectives and enabling initiation of the Oz-V Phase 3 study with a partner. This underscores the potential of the CAB platform technology, which includes clinical readouts on our dual CAB EpCAM T-cell engager [BA3182] later this year.”

What Phase 3 Trial Design and Pathway to Approval Were Agreed Upon?

The prospective, open-label phase 3 trial will enroll approximately 300 patients with OPSCC, who will be randomly assigned 1:1 to receive either Oz-V at a dose of 1.8 mg/kg every other week or investigator’s choice of cetuximab (Erbitux), docetaxel, or methotrexate monotherapy.

The FDA’s guidance includes a path for accelerated approval of Oz-V based on an interim analysis of enrolled patients. This will require a statistically significant improvement of confirmed overall response rate (ORR) by blinded independent central review (BICR), supported by an adequately characterized duration of response (DOR). For full approval, the primary end point will be a statistically significant improvement in overall survival (OS).

What Is Already Known About the Efficacy of Oz-V in OPSCC?

Oz-V is currently under evaluation in the multicenter, open-label, single-arm, phase 2 BA3021-002 trial (NCT05271604), which enrolled adult patients with histologically or cytologically confirmed recurrent or metastatic stage III/IV HNSCC expressing ROR2 who have progressed on no more than 1 PD-L1 inhibitor alone or in combination.3,4

Previously reported findings from this trial, shared during the 2025 ASCO Annual Meeting, showed antitumor activity with Oz-V at a dose of 1.8 mg/kg every 2 weeks among patients with heavily pretreated HPV-positive OPSCC (n = 20). At the data cutoff of May 14, 2025, the ORR with Oz-V was 45% (n = 5 of 11), including a confirmed complete response rate of 27%. The disease control rate was 100%, and follow-up is ongoing.4 The median OS was 11.6 months, the median progression-free survival was 4.7 months, and the median DOR was 9.9 months.

These results compare favorably to other studies in this patient population using either cetuximab, docetaxel, or methotrexate monotherapy, which have reported ORRs ranging from 0% to 3.4% and a median OS of 4.4 months.

In the full HNSCC dataset (n = 40), most adverse effects (AEs) were low grade. The most frequently reported AEs were fatigue (57%) and anemia (32%). At the 1.8 mg/kg dose, 15% of patients have experienced grade 3 or higher treatment-related AEs (TRAE) to date. No treatment-related serious AEs have been observed, and only 1 patient discontinued treatment due to a TRAE.

References

1. BioAtla announces regulatory update on clinical 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. September 8, 2025. Accessed September 9, 2025. https://ir.bioatla.com/news-releases/news-release-details/bioatla-announces-regulatory-update-clinical-development-plan
2. 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. July 23, 2024. Accessed September 9, 2025. https://ir.bioatla.com/news-releases/news-release-details/bioatla-granted-fda-fast-track-designation-ozuriftamab-vedotin
3. A phase 2 open-label study of conditionally active biologic ozuriftamab vedotin (BA3021) in failed PD-1/L1 treatment of patients with recurrent or metastatic squamous cell carcinoma of the head and neck. J Clin Oncol. 2023;41(16):TPS6107. doi:10.1200/JCO.2023.41.16_suppl.TPS6107
4. BioAtla presents phase 2 ozuriftamab vedotin (oz-v) clinical trial data demonstrating compelling antitumor activity in HPV-associated oropharyngeal squamous cell carcinoma (HPV+ OPSCC) at the 1.8 mg/kg q2w dosing regimen. News release. BioAtla. June 2, 2025. Accessed September 9, 2025.https://ir.bioatla.com/news-releases/news-release-details/bioatla-presents-phase-2-ozuriftamab-vedotin-oz-v-clinical-trial