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

Head and Neck Cancer Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06056310
• Other study ID #: MS202359_0025
• Secondary ID: 2023-505796-76-0
• Status: Recruiting
• Phase: Phase 1
• Start date: January 18, 2024
• Est. completion date: April 16, 2025

Study information

• Verified date: June 2024
• Source: EMD Serono
• Contact: US Medical Information
• Phone: 888-275-7376
• Email: eMediUSA[@]emdserono.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: April 16, 2025
• Est. primary completion date: April 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Head and Neck Cancer
• Head and Neck Neoplasms

Intervention

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.
• 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

Locations

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

Sponsors (2)

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

Countries where clinical trial is conducted

United States,  Belgium,  Israel,  Korea, Republic of,  Spain,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants with Dose limiting toxicity (DLT)-like events		From Day 1 up to 5 Weeks
Secondary	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)
Secondary	Absolute values and changes in estimated glomerular filtration rate (eGFR)		From Screening up to Cycle 3 Day 4 (Day 67)
Secondary	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
Secondary	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
Secondary	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
Secondary	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

External Links

•   Trial Awareness and Transparency website