Phase 1b Safety Study of Xevinapant, Weekly Cisplatin, and RT in Participants With Unresected LA SCCHN (HyperlynX)

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the tolerability and safety of Xevinapant when added to weekly cisplatin-based concurrent chemoradiotherapy (CRT) in the treatment of participants with unresectable locally advanced squamous cell carcinoma of the head and neck, suitable for definitive chemoradiotherapy.

Official Title
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A Single Arm, Open Label, Phase 1b Study of Xevinapant in Combination With Weekly Cisplatin and Intensity-modulated Radiotherapy to Assess Safety and Tolerability in Participants With LA SCCHN, Suitable for Definitive Chemoradiotherapy (HyperlynX)

Conditions
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Head and Neck Cancer

Intervention / Treatment
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* Drug: Xevinapant
* Drug: Cisplatin
* Radiation: intensity-modulated radiation therapy (IMRT)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants having an Eastern Cooperative Oncology Group Performance Score (ECOG PS) of 0 - 1 Histologically confirmed diagnosis in previously untreated Locally Advanced Squamous Cell Carcinoma of Head and neck (LA SCCHN) patient (Stage III, IVA, or IVB according to the American Joint Committee on Cancer [AJCC]/ Tumor Nodes and metastases (TNM) Staging System, 8th Edition) suitable for definitive Chemoradiotherapy (CRT), with one of the following primary sites: oropharynx (OPC) Human Papillomavirus (HPV)-negative, hypopharynx, and larynx Participant should be able to swallow liquids or has an adequately functioning feeding tube, gastrostomy, or jejunostomy in place. For participants requiring liquid nutrition at baseline or during the study including the follow-up period, access to liquid nutrition supply should be ensured Participant with evaluable tumor burden (measurable and/or non-measurable tumor lesions) assessed by CT scan and/or MRI, based on RECIST v 1.1. Adequate hematological, hepatic, and renal function as defined in the protocol Other protocol defined inclusion criteria could apply Exclusion Criteria: Primary tumor of nasopharyngeal, paranasal sinuses, nasal, or oral cavity, salivary, thyroid, or parathyroid gland pathologies, skin, or unknown primary site Metastatic disease (Stage IVC as per AJCC/TNM, 8th Edition) Existing need of a hearing aid or greater than or equal to (>=) 25 decibel shift over 2 contiguous frequencies on a pretreatment hearing test as clinically indicated Known history of infection with human immunodeficiency virus (HIV). If unknown history of HIV, an HIV screening test is to be performed and participants with positive serology for HIV-1/2 must be excluded Known gastrointestinal disorder with clinically established malabsorption syndrome and major gastrointestinal surgery in the last 12 months that may limit oral absorption Other protocol defined exclusion criteria could apply

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Xevinapant + Cisplatin + IMRT<br>Participants will receive xevinapant once daily from Day 1 to Day 14, per 3-week cycle (Each cycle is of 3 weeks). The first three cycles are given in combination with weekly cisplatin and radiotherapy, followed by 3 cycles of monotherapy xevinapant. | Drug: Xevinapant<br>* Participants will receive xevinapant once daily from Day 1 to Day 14, per 3-week cycle (Each cycle is of 3 weeks). The first three cycles are given in combination with weekly cisplatin and radiotherapy, followed by 3 cycles of monotherapy xevinapant.<br>* Other names: Debio 1143;Drug: Cisplatin<br>* Participants will receive weekly cisplatin for 7 weeks on Cycle 1 Day 2 (C1D2), C1D9, C1D16, C2D2, C2D9, C2D16, and C3D2).<br>Radiation: intensity-modulated radiation therapy (IMRT)<br>* Participants will receive 70 Gray (Gy) of IMRT in 35 fractions, 2 Gy/fraction, 5 days/week<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Dose limiting toxicity (DLT)-like events |  | From Day 1 up to 5 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Adverse Events (AEs) and Treatment-Related AEs (TRAE) |  | From Day 1 up to 18 weeks (Each cycle is of 3 Weeks) | 
| Absolute values and changes in estimated glomerular filtration rate (eGFR) |  | From Screening up to Cycle 3 Day 4 (Day 67) | 
| Objective Response (OR) According to Response Evaluation Criteria in Solid Tumor (RECIST) version 1.1 criteria as assessed by Investigator |  | Time from first administration of study intervention until Progressive Disease (PD) or death, whichever is earlier assessed approximately up to 1.6 years | 
| Progression Free Survival (PFS) According to RECIST version 1.1 Criteria as Assessed by Investigator |  | Time from first administration of study intervention until PD or death, whichever is earlier assessed approximately up to 1.6 years | 
| Locoregional Control (LRC) According to RECIST version 1.1 Criteria As assessed by Investigator | LRC is defined as the time from date of the first treatment until date of the first occurrence of progression at the site of the primary tumor or the locoregional lymph nodes. | From randomization to the earliest between PFS event (progression at the site of the primary tumor or the locoregional lymph nodes) or End of Study assessed approximately up to 1.6 years | 
| Time to Subsequent Systemic Cancer Treatments |  | From randomization to the earliest between PFS event (progression at the site of the primary tumor or the locoregional lymph nodes) or End of Study, assessed approximately up to 1.6 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Unresected, Combination with CRT, Stage III, Stage IVA, Stage IVB, Oropharynx, Hypopharynx, Larynx