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

NCT06056310 | Terminated Phase 1 Results DMC FDA Drug

• 2 other identifiers: MS202359_00252023-505796-76-00
• Study Type: interventional
• Target: 18
• Locations: 6 countries
• Sites: 23

Brief Summary

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.

Conditions

Head and Neck Cancer

Keywords

Unresected; Combination with CRT; Stage III; Stage IVA; Stage IVB; Oropharynx; Hypopharynx; Larynx

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

• Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment-Related TEAEs

  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

  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

  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

  Up to approximately 6 months

• Progression Free Survival (PFS) According to RECIST Version 1.1 Criteria as Assessed by Investigator

  Time from randomization to the first documented disease progression, or death due to any cause, whichever occurs first (up to approximately 6 months)

Study Arms (1)

Xevinapant + Cisplatin + IMRT

EXPERIMENTAL

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; Drug: Cisplatin; Radiation: intensity-modulated radiation therapy (IMRT)

Interventions

Xevinapant DRUG

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.

Also known as: Debio 1143

Xevinapant + Cisplatin + IMRT

Cisplatin DRUG

Participants will receive weekly cisplatin for 7 weeks on Cycle 1 Day 2 (C1D2), C1D9, C1D16, C2D2, C2D9, C2D16, and C3D2).

Xevinapant + Cisplatin + IMRT

intensity-modulated radiation therapy (IMRT) RADIATION

Participants will receive 70 Gray (Gy) of IMRT in 35 fractions, 2 Gy/fraction, 5 days/week

Xevinapant + Cisplatin + IMRT

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• EMD Serono Research & Development Institute, Inc.: lead
• Merck KGaA, Darmstadt, Germany: collaborator

Study Sites (23)

Mount Sinai Comprehensive Cancer Center

Miami Beach, Florida, 33140, United States

Location

Karmanos Cancer Institute - PARENT

Detroit, Michigan, 48201, United States

Location

Montefiore Medical Center PRIME

The Bronx, New York, 10467, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Avera McKennan Hospital and University Health Center

Sioux Falls, South Dakota, 57105, United States

Location

Uza - Parent

Edegem, Belgium

Location

Universitair Ziekenhuis Gent - Medical Oncology

Ghent, Belgium

Location

Centre Hospitalier de l'Ardenne - PARENT

Libramont, Belgium

Location

Vitaz

Sint-Niklaas, Belgium

Location

Hadassah University Hospital - Ein Kerem

Jerusalem, Israel

Location

Pusan National University Hospital

Busan, South Korea

Location

Seoul National University Bundang Hospital

Seongnam, South Korea

Location

Konkuk University Medical Center

Seoul, South Korea

Location

Severance Hospital Yonsei University Health System

Seoul, South Korea

Location

Pusan National University Yangsan Hospital

Yangsan, South Korea

Location

ICO Girona - Hospital Universitari de Girona Dr Josep Trueta - Servicio de Oncologia Medica

Girona, Spain

Location

Clinica Universidad de Navarra (MAD) - Oncology Service

Madrid, Spain

Location

Hospital Universitario Fundacion Jimenez Diaz - Oncology

Madrid, Spain

Location

Hospital Universitario Virgen del Rocio - Oncology Service

Seville, Spain

Location

Kaohsiung Medical University Chung-Ho Memorial Hospital

Kaohsiung City, Taiwan

Location

China Medical University Hospital

Taichung, Taiwan

Location

National Taiwan University Hospital

Taipei, Taiwan

Location

Taipei Veterans General Hospital

Taipei, Taiwan

Location

Related Links

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

MeSH Terms

Conditions

Head and Neck Neoplasms; Laryngeal Diseases

Interventions

N-benzhydryl-5-(2-(methylamino)propanamido)-3-(3-methylbutanoyl)-6-oxodecahydropyrrolo(1,2-a)(1,5)diazocine-8-carboxamide; Cisplatin; Radiotherapy, Intensity-Modulated

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Otorhinolaryngologic Diseases

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Radiotherapy, Conformal; Radiotherapy, Computer-Assisted; Radiotherapy; Therapeutics

Results Point of Contact

• Title: Communication Center
• Organization: Merck Healthcare KGaA, Darmstadt Germany, an affiliate of Merck KGaA, Darmstadt, Germany

service@emdgroup.com

+49-6151-72-5200

Study Officials

• Medical Responsible

  EMD Serono Research & Development Institute, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 20, 2023
• First Posted: September 28, 2023
• Study Start: January 18, 2024
• Primary Completion: August 20, 2024
• Study Completion: August 20, 2024
• Last Updated: September 29, 2025
• Results First Posted: September 29, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

BE (4); US (5); KR (5); TW (4); IL (1); ES (4)