FDA Fast Tracks Ozuriftamab Vedotin in Recurrent/Metastatic HNSCC

• A fast track designation has been granted to ozuriftamab vedotin (CAB-ROR2-ADC; BA3021) from the FDA for the treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC).
• Ozuriftamab vedotin is an ROR2-targeted antibody-drug conjugate (ADC).
• The agent is currently undergoing evaluation in the phase 2 BA3021-002 trial (NCT05271604).

Ozuriftamab vedotin (CAB-ROR2-ADC; BA3021) has gained a fast track designation from the FDA for the treatment of patients with recurrent or metastatic HNSCC that experienced disease progression on or following treatment with platinum-based chemotherapy and a PD-(L)1 inhibitor.¹

A phase 2 trial titled BA3021-002 is evaluating the agent’s safety and efficacy in treatment-refractory patients with HNSCC.² In the study, 33 patients were enrolled who had HNSCC and treated with the agent at a dose of 1.8 mg/kg every 3 weeks (n = 21) and once every 2 weeks (n = 12) regimens. Among the 29 evaluable patients, patients received a median of 3 prior lines of treatment.

To date, there have been 11 responses at the combined dose regimens, including 5 that are confirmed and 1 complete response. Of the 5 responders that are confirmed and 6 that are unconfirmed, the median number of prior treatments was 2 and 3, respectively. This shows that patients who are less heavily pretreated were generally more likely to receive conformational scans. Further, the disease control rate (DCR) among these patients was 86%.

“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,” said Jay M. Short, PhD, chairman, chief executive officer, and co-founder of BioAtla, in a press 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.”

Ozuriftamab vedotin is a conditionally and reversible active ADC that is directed against ROR2. ROR2 is a transmembrane receptor tyrosine kinase that works as a noncanonical Wnt5A signaling receptor and is expressed in head and neck cancer, lung cancer, triple-negative breast cancer, and melanoma. The overexpression of ROR2 is associated with poor prognosis and resistance to chemotherapy and immunotherapy.

About the Phase 2 BA3021-002 Trial

BA3021-002 is a multicenter, open-label, single-arm, phase 2 trial evaluating ozuriftamab vedotin for the treatment of patients aged 18 years or older who have histologically or cytologically confirmed recurrent or metastatic stage III/IV HNSCC that expresses ROR2.³ The study now has an estimated enrollment of 80 patients.

To be included in the study, patients must have an ECOG performance status of 0 or 1, have measurable disease by RECIST 1.1 criteria, have progressed on no more than 1 PD-(L)1 inhibitor alone or in combination, and cannot be amenable to local therapy with curative intent. Patients also must have adequate liver, renal, and hematologic functions.

Once enrolled, patients will receive ozuriftamab vedotin via intravenous infusion either alone or in combination with platinum chemotherapy at 1 of 2 dosing schedules.

The coprimary end points of the study include overall response rate and safety, including adverse events or serious adverse events as assessed by CTCAE v5. Key secondary end points being assessed are progression-free survival, duration of response, best overall response, DCR, overall survival, and time to treatment response.

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. BioAtla, Inc. July 23, 2024. Accessed July 24, 2024. https://tinyurl.com/3kderfw6

2. BioAtla reports first quarter 2024 financial results and highlights recent progress. News release. BioAtla, Inc. May 14, 2024. Accessed July 24, 2024. https://tinyurl.com/2fz8668a

3. 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 24, 2024. https://clinicaltrials.gov/study/NCT05271604