FDA Grants Fast Track Designation to Ozuriftamab Vedotin in Recurrent/Metastatic HNSCC

Jay M. Short, PhD

The FDA has granted fast track designation to the ROR2-targeted antibody-drug conjugate (ADC) ozuriftamab vedotin (CAB-ROR2-ADC; BA3021) as a potential treatment option for patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) who experienced disease progression on or after treatment with platinum-based chemotherapy and a PD-(L)1 inhibitor.¹

Ozuriftamab vedotin is a conditionally and reversible active agent directed at ROR2, a transmembrane receptor tyrosine kinase that functions as a noncanonical Wnt5A signaling receptor. ROR2 is expressed in various solid tumors, such as head and neck cancer, lung cancer, triple-negative breast cancer, and melanoma; its overexpression is linked to poor prognosis and resistance to chemotherapy and immunotherapy.

The safety and efficacy of this agent is currently under investigation in the phase 2 BA3021-002 trial (NCT05271604). Early results from this study have shown clinical activity with ozuriftamab vedotin along with a manageable safety profile in treatment-refractory patients with HNSCC.

As of the data cutoff of May 14, 2024, ozuriftamab vedotin administered at 1.8 mg/kg twice every 3 weeks (n = 21) or once every 2 weeks (n = 12) produced a total of 11 responses among evaluable patients (n = 29), 5 of which were confirmed and 1 of which was a complete response. Among the 5 confirmed and 6 unconfirmed responders, the median number of prior treatment lines was 2 and 3, respectively. The disease control rate (DCR) was 86%.²

“The FDA’s decision is an important recognition of the potential of our CAB-ROR2-ADC, ozuriftamab vedotin. There remains a significant unmet need in refractory head and neck cancer where previous treatments have failed and current outcomes are suboptimal with low response rates,” Jay M. Short, PhD, chairman, chief executive officer and co-founder of BioAtla, stated in a news release.¹ “To date, ozuriftamab vedotin has shown promising clinical activity in treatment-refractory patients with HNSCC who had a median of 3 prior lines of therapy. In addition, ozuriftamab vedotin continues to have a manageable safety profile with no new safety signals. We look forward to discussing with the FDA plans for a potential registrational trial in the second half of this year.”

The multicenter, open-label, single-arm phase 2 study is enrolling patients at least 18 years of age with histologically or cytologically confirmed recurrent or metastatic stage III/IV HNSCC expressing ROR2.^3,4 Patients must have progressed on no more than 1 PD-(L)1 inhibitor alone or in combination; have measurable disease by RECIST 1.1 criteria; have an ECOG performance status of 0 or 1; and must not be amenable to local therapy with curative intent. Eligible primary tumor locations include the oropharynx, oral cavity, hypopharynx, and larynx; patients with a primary tumor site of the nasopharynx are excluded from the study.

The study plans to enroll approximately 40 patients, with 20 assigned to each cohort according to prior receipt of a PD-(L)1 inhibitor. Ozuriftamab vedotin will be administered intravenously to patients either alone or in combination with platinum chemotherapy at 1 of 2 dosing schedules.³

Overall response rate and safety serve as the study’s coprimary end points. Key secondary end points include progression-free survival, overall survival, duration of response, best overall response, DCR, time-to-treatment response, and percent change in tumor size from baseline. Pharmacokinetics, the relationship between tumor ROR2 status and clinical response with the study drug. immunogenicity, and potential candidate tumor or blood-based biomarkers that correlate with the agent’s antitumor activity serve as exploratory end points.

Ozuriftamab vedotin is also being evaluated in the phase 1/2 BA3021-001 trial (NCT03504488) both alone and in combination with nivolumab (Opdivo) in patients with advanced solid tumors.⁵

References

1. 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. July 23, 2024. Accessed July 23, 2024. https://ir.bioatla.com/news-releases/news-release-details/bioatla-granted-fda-fast-track-designation-ozuriftamab-vedotin
2. BioAtla reports first quarter 2024 financial results and highlights recent progress. May 14, 2024. Accessed July 23, 2024. https://ir.bioatla.com/news-releases/news-release-details/bioatla-reports-first-quarter-2024-financial-results-and
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. A phase 2 open label study of BA3021 in patients with recurrent or metastatic squamous cell carcinoma of the head and neck. ClinicalTrials.gov. Updated September 29, 2023. Accessed July 23, 2024. https://clinicaltrials.gov/study/NCT05271604
5. CAB-ROR2-ADC safety and efficacy study in patients with TNBC or head & neck cancer (Ph1) and NSCLC or melanoma (Ph2). ClinicalTrials.gov. Updated January 31, 2024. Accessed July 23, 2024. https://clinicaltrials.gov/study/NCT03504488