868P - Phase II trial of ozuriftamab vedotin (BA3021), a conditionally active biologic (CAB)-ROR2-ADC, in patients with recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN)

Background

Few patients (pts) with R/M SCCHN respond to salvage therapy. ROR2 is a receptor tyrosine kinase that is overexpressed in many solid tumors, including lung, head and neck, breast, and melanoma, and is associated with therapeutic resistance. CABs are designed to reduce off-tumor toxicity and immunogenicity, avoid tissue-mediated drug disposition, and improve pharmacokinetics (Chang HW, et al. PNAS. 2021). BA3021, a CAB-ROR2-ADC, conditionally and reversibly binds to ROR2 and internalizes under low pH conditions in tumors.

Methods

In this open-label phase II study, pts with R/M SCCHN and measurable disease by RECIST v1.1 who previously experienced progression on a PD-1 inhibitor received BA3021 at 1.8 mg/kg every other week (Q2W). Once Q2W enrollment was complete, pts enrolled in a more intensive dosing regimen of days 1 and 8 of a 3-week cycle (2Q3W). Efficacy was assessed via best overall response, which included complete response (CR), partial response (PR), and stable disease (SD) per RECIST v1.1 in evaluable pts (those who had ≥1 tumor scan after receiving study drug). Treatment-emergent adverse events (TEAEs) were graded using NCI CTCAE v5.0.

Results

As of March 13, 2024, 31 pts with a median of 3 prior lines of therapy received BA3021 either Q2W (n=12) or 2Q3W (n=19) for a median of 58 days. Overall, among 25 pts evaluable for efficacy, 8 responders (32%; 1 CR and 7 PR; confirmed and unconfirmed) were reported, and 10 pts had SD. In the Q2W cohort (12 evaluable pts), 1 CR, 2 PR, and 4 SD were reported. In the 2Q3W cohort (13 evaluable pts), 5 PR and 6 SD were reported. The most frequent TEAEs were fatigue (55%), nausea (29%), anemia (26%), decreased appetite (26%), and diarrhea (26%). Nineteen pts had grade 3‒4 TEAEs; the most frequent (10% each) were anemia, hyponatremia, and hypoxia. Related grade 3 peripheral neuropathy led to study drug discontinuation in 1 pt. As of the data cut, 11 pts remained on BA3021 (2 in Q2W and 9 in 2Q3W).

Conclusions

Treatment with BA3021 yielded promising antitumor activity with a manageable tolerability profile in heavily pretreated pts (median 3 prior regimens) with R/M SCCHN. Further evaluation of BA3021 in earlier-stage pts is planned.

Clinical trial identification

NCT05271604 EudraCT 2022-001532-28.

Editorial acknowledgement

Alec Jacobson, MD, from MedLogix Communications, a Citrus Health Group, Inc, company (Chicago, IL).

Legal entity responsible for the study

BioAtla, Inc.

Funding

BioAtla, Inc.

Disclosure

W. Wong: Financial Interests, Research Funding: BioAtla, Hookipa. D.R. Adkins: Financial Interests, Speaker, Consultant, Advisor: Blueprint Medicine, Boehringer Ingelheim, Coherus Biosciences, Cue Biopharma, Eisai Europe, Exelixis, Gilead Sciences, Immunitas, Inhibrx, Kura Oncology, Merck, Targimmune Therapeutics, Vaccinex, Xilio Therapeutics; Financial Interests, Institutional, Research Funding: Adlai Nortye, Alentis, AstraZeneca, BeiGene, BioAtla, Blueprint Medicine, Boehringer Ingelheim, Calliditas, Celgene/BMS, Cofactor Genomics, Coherus Biosciences, Cue Biopharma, Daiichi Sankyo, Debiopharm, Eli Lilly, Epizyme, Exelixis, Genmab, Gilead Sciences, GSK, Hookipa, Immutep, Inhibrx, ISA Pharmaceuticals, Janux, Johnson & Johnson, Kura Oncology, Merck, Merus, Natco, Novartis, Pfizer, Roche, Seagen, Tizona, Vaccinex, Xilio Therapeutics; Financial Interests, Institutional, Local PI: Adlai Nortye, Alentis, AstraZeneca, BeiGene, BioAtla, Blueprint Medicine, Boehringer Ingelheim, Calliditas, Celgene/BMS, Cofactor Genomics, Coherus Biosciences, Cue Biopharma, Daiichi Sankyo, Debiopharm, Eli Lilly, Epizyme, Exelixis, Genmab, Gilead Sciences, GSK, Hookipa, Immutep, Inhibrx, ISA Pharmaceuticals, Janux, Johnson & Johnson, Kura Oncology, Merck, Merus, Natco, Novartis, Pfizer, Roche, Seagen, Tizona, Vaccinex, Xilio Therapeutics; Other, Membership or affiliation: NCCN Head and Neck Panel. J. Lorch: Financial Interests, Speaker, Consultant, Advisor: Bayer, Eisai, Genentech, Novartis; Financial Interests, Institutional, Research Funding: Bayer, Bristol Myers Squibb, Millennium, Novartis. J.S. Grewal: Financial Interests, Other, Honoraria: BMS, Ipsen, Lilly, OncLive; Financial Interests, Speaker, Consultant, Advisor: OncLive; Financial Interests, Speaker’s Bureau: BMS, Ipsen, Lilly, OncLive; Financial Interests, Expert Testimony: Monsanto; Financial Interests, Other, Travel, accommodations, expenses: Vaccibody, Nykode Therapeutics. A.L. Ho: Financial Interests, Personal, Invited Speaker, discussed head and neck cancer therapies: Chinese American Hematologist and Oncologist Network; Financial Interests, Personal, Invited Speaker, Discussed salivary cancer therapies: Lurie Cancer Center (Northwestern); Financial Interests, Personal, Invited Speaker, discussed thyroid cancer therapies: Physician Education Resource; Financial Interests, Personal, Invited Speaker, Discussed thyroid cancer therapies: Endocrine Society; Financial Interests, Personal, Invited Speaker, Discussed head and neck cancer therapies: University of Pittsburgh Medical Center; Financial Interests, Personal, Invited Speaker, Discussed thyroid cancer therapeutics: New York University; Financial Interests, Personal, Advisory Board, Serve on DSMC: Affyimmune; Financial Interests, Personal, Other, Serve on the NCI Head and Neck Steering Committee: National Cancer Institute; Financial Interests, Personal, Advisory Board, Member of advisory board: Exelixis, Remix Therapeutics, Elevar Therapeutics, Prelude Therapeutics, Eisai, Ayala, Kura Oncology; Financial Interests, Personal, Other, Member of Safety Monitoring Committee: Kura Oncology; Financial Interests, Personal, Advisory Board, Member of advisory board: Merck; Financial Interests, Personal, Other, Consultant: ExpertConnect; Financial Interests, Personal, Advisory Board, Member of advisory board and consulting: Rgenta; Financial Interests, Personal, Advisory Board, Advisory Board: Coherus; Financial Interests, Personal, Advisory Board: Nested Therapeutics; Financial Interests, Personal, Full or part-time Employment: Memorial Sloan Kettering Cancer Center; Financial Interests, Institutional, Other, Listed as inventor for: Memorial Sloan Kettering Cancer Center; Financial Interests, Institutional, Coordinating PI, Serve as PI. also served on paid advisory board: Ayala; Financial Interests, Institutional, Coordinating PI, Serve as trial PI, also serve on paid SMC/advisory board: Kura Oncology; Financial Interests, Institutional, Local PI, Trial PI and served on an advisory board: Elevar Therapuetics; Financial Interests, Institutional, Coordinating PI, PI of IIT: Novartis, Merck, Bristol Meyer Squibb; Financial Interests, Institutional, Coordinating PI, PI of several IIT trials: Bayer; Financial Interests, Institutional, Coordinating PI, PI of trial: Bioatla, TILT Biotherapeutics, Genentech Roche, Astellas, Celldex; Financial Interests, Institutional, Local PI, PI of trial: OncC4; Financial Interests, Institutional, Coordinating PI, PI of several IITs: AstraZeneca; Financial Interests, Institutional, Coordinating PI, PI of trial and was part of paid advisory board: Eisai; Financial Interests, Institutional, Local PI, co-PI of trial: Poseida Therapuetics; Financial Interests, Institutional, Local PI: Hookipa; Financial Interests, Institutional, Coordinating PI, PI of IST clinical trial: Verastem; Financial Interests, Institutional, Coordinating PI, PI of Remix sponsored trial: Remix Therapeutics; Non-Financial Interests, Advisory Role: Cellestia, Inxmed; Non-Financial Interests, Member of Board of Directors: International Thyroid Oncology Group; Non-Financial Interests, Leadership Role: International Rare Cancer Initiative; Non-Financial Interests, Leadership Role, for the head and neck working group: Alliance for Clinical Trials in Oncology. K. Chen, K. Aysola: Other, Full or part-time Employment: BioAtla. J. Thomas: Financial Interests, Speaker, Consultant, Advisor: Kura Oncology, Tasly Pharmaceuticals. All other authors have declared no conflicts of interest.