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

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.

Brief Title

Categories

Brain, Spine & Nerve Cancers

Cancer

Head & Neck

Endocrine System Cancers

Asthma and Other Respiratory Diseases

Lung & Chest Cancers

COVID-19

Lung

Completion Date

2024-08-20

Completion Date Type

Actual

Conditions

Head and Neck Cancer

Eligibility Criteria

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

Inclusion Criteria

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

Gender

All

Gender Based

false

Keywords

Unresected

Combination with CRT

Stage III

Stage IVA

Stage IVB

Oropharynx

Hypopharynx

Larynx

Healthy Volunteers

No

Last Update Post Date

Mon, 09/29/2025 - 12:00

Last Update Post Date Type

Estimated

Last Update Submit Date

Mon, 09/08/2025 - 12:00

Minimum Age

18 Years

NCT Id

NCT06056310

Org Class

Industry

Org Full Name

EMD Serono

Org Study Id

MS202359_0025

Overall Status

Terminated

Phases

Phase 1

Primary Completion Date

Tue, 08/20/2024 - 12:00

Primary Completion Date Type

Actual

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)

Primary Outcomes

Outcome Description

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.

Outcome Measure

Number of Participants With Dose Limiting Toxicity (DLT)-Like Events

Outcome Time Frame

Time from the first dose of study intervention day upto 35 days (5 weeks)

Secondary Ids

Secondary Id

2023-505796-76-00

Secondary Outcomes

Outcome Description

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.

Outcome Time Frame

Screening up to end of treatment (Day 134) and then follow up every 3 months (assessed up to maximum 6 months)

Outcome Measure

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

Outcome Description

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.

Outcome Time Frame

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)

Outcome Measure

Absolute Estimated Glomerular Filtration Rate (eGFR) Values

Outcome Description

eGFR creatinine was evaluated using CKD-EPI formula. Absolute change from baseline in eGFR was presented.

Outcome Time Frame

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)

Outcome Measure

Absolute Change From Baseline in eGFR

Outcome Description

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.

Outcome Time Frame

Up to approximately 6 months

Outcome Measure

Objective Response (OR) According to Response Evaluation Criteria in Solid Tumor (RECIST) Version 1.1 Criteria as Assessed by Investigator

Outcome Description

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.

Outcome Time Frame

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

Outcome Measure

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

Outcome Description

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.

Outcome Time Frame

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

Outcome Measure

Locoregional Control (LRC) According to RECIST Version 1.1 Criteria As Assessed by Investigator

Outcome Description

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).

Outcome Time Frame

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

Outcome Measure

Time to Subsequent Systemic Cancer Treatments