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

Phase 1

Terminated

Conditions: Head and Neck Cancer

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

Registration Number: NCT06056310

Lead Sponsor: EMD Serono Research & Development Institute, Inc.

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 18

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 & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Xevinapant + Cisplatin + IMRT	intensity-modulated radiation therapy (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.
Xevinapant + Cisplatin + IMRT	Cisplatin	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.
Xevinapant + Cisplatin + IMRT	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.

Primary Outcome Measures

Name	Time	Method
Number of Participants With Dose Limiting Toxicity (DLT)-Like Events	Time from the first dose of study intervention day upto 35 days (5 weeks)	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.

Secondary Outcome Measures

Name	Time	Method
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)	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.
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)	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.
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)	eGFR creatinine was evaluated using CKD-EPI formula. Absolute change from baseline in eGFR was presented.
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	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.
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)	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.
Locoregional Control (LRC) According to RECIST Version 1.1 Criteria As Assessed by Investigator	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	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 to Subsequent Systemic Cancer Treatments	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	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).

Trial Locations

Locations (23): Mount Sinai Comprehensive Cancer Center
🇺🇸
Miami Beach, Florida, United States
Karmanos Cancer Institute - PARENT
🇺🇸
Detroit, Michigan, United States
Montefiore Medical Center PRIME
🇺🇸
The Bronx, New York, United States
Cleveland Clinic
🇺🇸
Cleveland, Ohio, United States
Avera McKennan Hospital and University Health Center
🇺🇸
Sioux Falls, South Dakota, United States
Uza - Parent
🇧🇪
Edegem, Belgium
Universitair Ziekenhuis Gent - Medical Oncology
🇧🇪
Ghent, Belgium
Centre Hospitalier de l'Ardenne - PARENT
🇧🇪
Libramont, Belgium
Vitaz
🇧🇪
Sint-Niklaas, Belgium
Hadassah University Hospital - Ein Kerem
🇮🇱
Jerusalem, Israel
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Mount Sinai Comprehensive Cancer Center
🇺🇸Miami Beach, Florida, United States