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

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)

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.

Study Overview

• Status: Terminated
• Conditions: Head and Neck Cancer
• Intervention / Treatment: Drug: Cisplatin; Radiation: intensity-modulated radiation therapy (IMRT); Drug: Xevinapant

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Edegem, Belgium
    • Uza - Parent
  • Ghent, Belgium
    • Universitair Ziekenhuis Gent - Medical Oncology
  • Libramont, Belgium
    • Centre Hospitalier de l'Ardenne - PARENT
  • Sint-Niklaas, Belgium
    • Vitaz
• Israel
  • Jerusalem, Israel
    • Hadassah University Hospital - Ein Kerem
• South Korea
  • Busan, South Korea
    • Pusan National University Hospital
  • Seongnam, South Korea
    • Seoul National University Bundang Hospital
  • Seoul, South Korea
    • Konkuk University Medical Center
  • Seoul, South Korea
    • Severance Hospital Yonsei University Health System
  • Yangsan, South Korea
    • Pusan National University Yangsan Hospital
• Spain
  • Girona, Spain
    • ICO Girona - Hospital Universitari de Girona Dr Josep Trueta - Servicio de Oncologia Medica
  • Madrid, Spain
    • Clinica Universidad de Navarra (MAD) - Oncology Service
  • Madrid, Spain
    • Hospital Universitario Fundacion Jimenez Diaz - Oncology
  • Seville, Spain
    • Hospital Universitario Virgen del Rocio - Oncology Service
• Taiwan
  • Kaohsiung City, Taiwan
    • Kaohsiung Medical University Chung-Ho Memorial Hospital
  • Taichung, Taiwan
    • China Medical University Hospital
  • Taipei, Taiwan
    • National Taiwan University Hospital
  • Taipei, Taiwan
    • Taipei Veterans General Hospital
• United States
  • Florida
    • Miami Beach, Florida, United States, 33140
      • Mount Sinai Comprehensive Cancer Center
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Karmanos Cancer Institute - PARENT
  • New York
    • The Bronx, New York, United States, 10467
      • Montefiore Medical Center Prime
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57105
      • Avera McKennan Hospital and University Health Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Xevinapant + Cisplatin + IMRT; 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: Cisplatin; Participants will receive weekly cisplatin for 7 weeks on Cycle 1 Day 2 (C1D2), C1D9, C1D16, C2D2, C2D9, C2D16, and C3D2).; Radiation: intensity-modulated radiation therapy (IMRT); Participants will receive 70 Gray (Gy) of IMRT in 35 fractions, 2 Gy/fraction, 5 days/week; Drug: Xevinapant; 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.; Other Names: Debio 1143

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Dose Limiting Toxicity (DLT)-Like Events	DLT-like events defined as any of the following treatment-related adverse events (AEs) or lab abnormalities occurring during the 5-week DLT-like assessment period and assessed as related to the study intervention: Grade 4 asymptomatic neutropenia more than (>) 7 days; Grade 2-3 febrile neutropenia; Grade 4 thrombocytopenia without bleeding more than and equal to (>=) 5 days or Grade 2-3 with bleeding or requiring transfusion; Grade 2-3 nonhematologic toxicity (e.g., renal impairment based on eGFR, Grade 4 skin toxicity/mucositis interfering with treatment); less than (<) 60% planned cumulative dose of xevinapant or cisplatin due to AE; >2-week Radiation therapy (RT) delay due to AE; Grade >=2 ototoxicity worsening >=2 grades from baseline and considered treatment-limiting; Hy's Law DILI; Grade >=3 lab abnormalities; any life-threatening or Grade 5 toxicity.	Time from the first dose of study intervention day upto 35 days (5 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment-Related TEAEs	AEs were defined as any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. TEAEs were defined as AEs emerging or worsening after start of treatment until 30 days after end of treatment. Adverse events were coded according to the latest available version of the Medical Dictionary for Regulatory Activities (MedDRA). Treatment-Related TEAEs was defined as any AE considered as related to study treatment.	Screening up to end of treatment (Day 134) and then follow up every 3 months (assessed up to maximum 6 months)
Absolute Estimated Glomerular Filtration Rate (eGFR) Values	eGFR creatinine was evaluated using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula. Absolute values in eGFR was presented. Here, mL/min/1.73 m^2 is defined as milliliters per minute per 1.73 square meters.	At Cycle1 Day 4 (C1D4), C1D11, C1D18, C2D1, C2D4, C2D11, C2D18, C3D1, C3D4, C4D1, C5D1, C6D1 and End of treatment (Day 134) (each cycle is of 3 weeks)
Absolute Change From Baseline in eGFR	eGFR creatinine was evaluated using CKD-EPI formula. Absolute change from baseline in eGFR was presented.	Baseline, C1D4, C1D11, C1D18, C2D1, C2D4, C2D11, C2D18, C3D1, C3D4, C4D1, C5D1, C6D1 and End of treatment (Day 134) (each cycle is of 3 weeks)
Objective Response (OR) According to Response Evaluation Criteria in Solid Tumor (RECIST) Version 1.1 Criteria as Assessed by Investigator	OR is defined as the number of participants who have a best overall response of complete response (CR) or partial response (PR) CR: Disappearance of target and non-target lesions and normalization of tumor markers. PR: At least a 30% decrease in the sum of measures (longest diameter for tumor lesions and short axis measure for nodes) of target lesions, taking as reference the baseline sum of diameters. Non target lesions must be non-progressive disease.	Up to approximately 6 months
Progression Free Survival (PFS) According to RECIST Version 1.1 Criteria as Assessed by Investigator	PFS was defined as the time from randomization to the first documented disease progression per RECIST 1.1 based on Blinded Independent Central Review (BICR), or death due to any cause, whichever occurs first. According to RECIST 1.1, progressive disease (PD) was defined as a 20% relative increase in the sum of diameters (SOD) of target lesions, taking as reference the nadir SOD and an absolute increase of >5 millimeter (mm) in the SOD, or the appearance of new lesions.	Time from randomization to the first documented disease progression, or death due to any cause, whichever occurs first (up to approximately 6 months)
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.	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 or End of Study, assessed approximately up to 6 months
Time to Subsequent Systemic Cancer Treatments	Time to subsequent systematic cancer treatments was defined as time from date of the first treatment administration until the start date of the first subsequent systemic cancer treatment for squamous cell carcinoma of the head and neck (SCCHN).	Time from date of the first treatment administration until the start date of the first subsequent systemic cancer treatment for SCCHN or End of study, assessed up to approximately 6 months

Collaborators and Investigators

• Sponsor: EMD Serono Research & Development Institute, Inc.
• Collaborators: Merck KGaA, Darmstadt, Germany
• Investigators: Study Director: Medical Responsible, EMD Serono Research & Development Institute, Inc.

Publications and helpful links

Helpful Links

• US Medical Information website, Medical Resources
• Trial Awareness and Transparency website

Study record dates

Study Major Dates

• Study Start (Actual): January 18, 2024
• Primary Completion (Actual): August 20, 2024
• Study Completion (Actual): August 20, 2024

Study Registration Dates

• First Submitted: September 20, 2023
• First Submitted That Met QC Criteria: September 20, 2023
• First Posted (Actual): September 28, 2023

Study Record Updates

• Last Update Posted (Estimated): September 29, 2025
• Last Update Submitted That Met QC Criteria: September 8, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Larynx; Stage III; Hypopharynx; Oropharynx; Stage IVA; Stage IVB; Unresected; Combination with CRT
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Otorhinolaryngologic Diseases; Head and Neck Neoplasms; Laryngeal Diseases; Therapeutics; Inorganic Chemicals; Chlorine Compounds; Nitrogen Compounds; Platinum Compounds; Radiotherapy; Radiotherapy, Conformal; Radiotherapy, Computer-Assisted; Cisplatin; Radiotherapy, Intensity-Modulated; N-benzhydryl-5-(2-(methylamino)propanamido)-3-(3-methylbutanoyl)-6-oxodecahydropyrrolo(1,2-a)(1,5)diazocine-8-carboxamide
• Other Study ID Numbers: MS202359_0025; 2023-505796-76-00 (Other Identifier: EU CTIS)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: We are committed to enhancing public health through responsible sharing of clinical trial data. Following approval of a new product or a new indication for an approved product in both the US and the European Union, the study sponsor and/or its affiliated companies will share study protocols, anonymized patient data and study level data, and redacted clinical study reports with qualified scientific and medical researchers, upon request, as necessary for conducting legitimate research. Further information on how to request data can be found on our website bit.ly/IPD21

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No