Phase III Xevinapant (Debio 1143) and Radiotherapy in Resected LA SCCHN, High Risk, Cisplatin-ineligible Participants (XRAY VISION)

• Status: Not yet recruiting
• Trial end date: 2031-01-25
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of this study is to demonstrate the superior efficacy of Xevinapant (Debio 1143) versus placebo when added to radiotherapy in the treatment of high-risk participants with resected locally advanced squamous cell carcinoma of the head and neck (LA SCCHN) who are ineligible to receive cisplatin-based chemoradiation concurrently. Study details include: Study duration: Participants will be followed until the last on-study participant reaches his/her 60-month post-randomization visit, a decision to end the study has been triggered, or until premature discontinuation from study, whichever occurs first. Treatment duration: 18 weeks, consisting of six 3-week cycles. Health measurement/observation: Improved Disease-Free Survival. Visit frequency: Weekly visit during combination therapy period, once every 3 weeks during monotherapy period, and every 3, 4, or 6 months during the Disease-Free Survival Follow-up period in Year 1, 2 and 3, or 4 and 5 (with telephone contact in between), respectively, and every 3 months (telephone visits allowed) during the Overall Survival Follow-up period.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: EMD Serono Research & Development Institute, Inc.
• Collaborator: Merck KGaA, Darmstadt, Germany

Criteria

Inclusion Criteria:

• Participants with Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0-1

• Participants with histologically confirmed squamous cell carcinoma with one of the following primary sites: oral cavity, oropharynx, hypopharynx or larynx. Participants have received surgery with curative intent on these sites in the past 4 to 8 weeks before start of treatment (Cycle 1 Day 1)

• Oropharynx (OPC) participants must have known human papillomavirus (HPV) status as determined by p16 expression using immunohistochemistry (ICH)

• Participants with no residual disease by computed tomography (CT) and 2-deoxy-2-[fluorine-18] fluoro-D-glucose positron emission tomography (18F-FDG-PET) and have a high risk of relapse with 1 or 2 of the following criteria, confirmed by local histopathology: • nodal extra-capsular extension (ECE) and positive resection margins (R1 or close margin less than or equal to (<=) 1 millimeter (mm)

• Are unfit to receive high-dose cisplatin by meeting one or more of the following criteria: 30 < estimated glomerular filtration rate (eGFR) < 60 milliliter per minute per 1.73 meter square (mL/min /1.73 m^2); History of hearing loss, defined as Grade >= 2 audiometric hearing loss. An audiogram is not required if one of the other criteria meets unfitness to receive high-dose cisplatin; Peripheral neuropathy > = Grade 2 and if >= 70 years, unfit according to G8 questionnaire (Score <= 14)

• Participants with adequate hematologic and hepatic function as defined in the protocol

• Other protocol-defined inclusion criteria could apply

Exclusion Criteria:

• Any condition, including any uncontrolled disease state other than SCCHN that in the Investigator's opinion constitutes an inappropriate risk or a contraindication for participation in the study or that could interfere with the study objectives, conduct, or evaluation

• Participant with incomplete surgery

• Primary tumor of nasopharyngeal, paranasal sinuses, nasal cavity, salivary, thyroid or parathyroid gland, skin or unknown primary site

• Prior definitive, neoadjuvant, concurrent or adjuvant (C)RT to the head and neck region which may jeopardize the primary tumor irradiation plan, or any other prior SCCHN systemic treatment, including investigational agents

• Participation in any clinical study within 28 days prior to screening or during participation in this study

• Known contraindication to undergoing positron emission tomography with 18F-FDG-PET-CT scans, or both contrast-enhanced MRI and contrast-enhanced CT scans

• Known allergy to Xevinapant (Debio 1143) or any excipient known to be present in Xevinapant (Debio 1143) or in the placebo formulation

• Other protocol-defined exclusion criteria could apply