XRay Vision: A Phase 3 Study of Xevinapant Plus Radiotherapy (RT) for High-risk, Cisplatin-ineligible Patients with Resected, Locally Advanced Squamous Cell Carcinoma of the Head and Neck (LA SCCHN)

Purpose/Objective(s) The current standard of care for patients (pts) with resected LA SCCHN who are at high-risk of disease recurrence and are cisplatin eligible is chemoradiotherapy (CRT; cisplatin + RT). For pts who cannot receive cisplatin, treatment options are limited, and there is currently no treatment specifically recommended by international guidelines. Xevinapant, a first-in-class, small-molecule inhibitor of apoptosis protein inhibitor, has been shown to restore cancer cell sensitivity to apoptosis, thereby enhancing the effects of chemotherapy and RT. In a randomized phase 2 study in pts with unresected LA SCCHN, xevinapant + CRT was associated with a 53% lower risk of death after 5 years of follow-up and a 67% lower risk of death or disease progression after 3 years of follow-up vs placebo + CRT. In preclinical SCCHN models, xevinapant + RT alone also demonstrated antitumor activity. These promising clinical and preclinical data provide a strong rationale for combining xevinapant + RT in cisplatin-ineligible pts with LA SCCHN. Materials/Methods XRay Vision (NCT05386550) is a randomized, double-blind, placebo-controlled, phase 3 study comparing xevinapant or placebo + intensity-modulated RT (IMRT) in pts with resected LA SCCHN who are ineligible for cisplatin and have a high risk of relapse. Eligible pts must have histologically confirmed cancer of the oral cavity, oropharynx, hypopharynx, or larynx; undergone surgery with curative intent 4–10 weeks before the start of treatment (if possible, it is recommended to start treatment within 8 weeks from surgery); high risk of relapse; no residual disease by CT scan; and ineligible for cisplatin (meeting ≥1 of the following criteria: eGFR