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Abstract
Background Pembrolizumab (pembro) ± chemotherapy is a standard-of-care first-line (1L) treatment option for recurrent/metastatic (R/M) PD-L1+ head and neck squamous cell carcinoma (HNSCC). Pembro monotherapy is often used in patients with a PD-L1 combined positive score (CPS) of ≥20. However, limited benefit has been observed in this subgroup, with an objective response rate (ORR) of <25% and median overall survival (OS) of <15 months.1 This highlights the high unmet need for more effective treatment options. INBRX-106 is a novel, hexavalent OX40 agonist designed to promote hyperclustering of OX40, which is a costimulatory receptor that plays a crucial role in amplifying and prolonging the antitumor immune response. Combining OX40 agonism with the PD-1 checkpoint inhibitor pembro may allow for continuation of the antitumor response potentiated by OX40 signaling. In an ongoing phase 1/2 study (NCT04198766), INBRX-106 + pembro has demonstrated a favorable safety profile, robust pharmacodynamics, and promising clinical activity in multiple tumor types, including R/M HNSCC. INBRX106-01-201 (NCT06295731), a phase 2/3 randomized study, will evaluate INBRX-106 + pembro vs pembro alone as 1L treatment in patients with R/M HNSCC (figure 1).
Methods Eligible patients will have HNSCC considered incurable with local therapies; no prior therapy in the R/M setting; a centrally confirmed PD-L1 CPS of ≥20; measurable disease by Response Evaluation Criteria in Solid Tumors version 1.1; and a primary tumor in the oral cavity, oropharynx, hypopharynx, or larynx. Up to 450 patients will be randomized 1:1 (stratified by disease status, human papillomavirus status, and Eastern Cooperative Oncology Group performance status) to INBRX-106 + pembro 200 mg every 3 weeks (q3w) or pembro (alone in the open-label phase 2 part or with placebo in the double-blind phase 3 part). If the phase 2 part shows compelling results for the primary efficacy endpoint (ORR) and supportive secondary safety and efficacy endpoints (eg, duration of response [DOR], progression-free survival [PFS] rate at 6 months, and clinical benefit rate [CBR]), the study can seamlessly proceed to the phase 3 part. The phase 3 part has dual primary efficacy endpoints of PFS and/or OS; secondary endpoints include ORR, DOR, CBR, time to chemotherapy, safety, and patient-reported quality of life. This study is currently enrolling; up to 35 sites are planned in the US, 25 in Europe, and 25 in Asia-Pacific.
Acknowledgements Medical writing assistance was provided by Jenna M. Gaska, PhD, of Nucleus Global, an Inizio company, and funded by Inhibrx Biosciences, Inc.
Trial Registration ClinicalTrials.gov identifier, NCT06295731.
Reference
Burtness B, Harrington KJ, Greil R, et al. Pembrolizumab alone or with chemotherapy versus cetuximab with chemotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-048): a randomised, open-label, phase 3 study. Lancet. 2019;394(10212):1915–1928.
Ethics Approval The study protocol was reviewed and approved by the institutional review board at each participating institution; all patients provided written informed consent.
Design of the phase 2/3 study INBRX106-01-201 (NCT06295731). ClinicalTrials.gov identifier, NCT06295731. Protocol version 1.0; January 31, 2024. INBRX-106 and pembro to be administered every 3 weeks. 1L, first line; CBR, clinical benefit rate; CPS, combined positive score; DOR, duration of response; ECOG PS, Eastern Cooperative Oncology Group performance status; HNSCC, head and neck squamous cell carcinoma; HPV, human papillomavirus; ORR, objective response rate; OS, overall survival; PD-L1, programmed cell death 1 ligand 1; pembro, pembrolizumab; PFS, progression-free survival; PFS6mo progression-free survival rate at 6 months; PRO, patient-reported outcome; R, randomized; R/M, recurrent/metastatic; TTCx, time to chemotherapy; Tx, treatment
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