NCT06056310 · REGISTRY CONDITION SEARCH

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

Found through the registry condition index, not selected as a treatment recommendation. This discovery collection was restricted to studies with posted results.

Phase: PHASE1
Status at capture: TERMINATED
Registry last update: 2025-09-29

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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

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

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outcome · POSTED

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

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outcome · POSTED

Absolute Estimated Glomerular Filtration Rate (eGFR) Values

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outcome · POSTED

Absolute Change From Baseline in eGFR

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outcome · POSTED

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

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outcome · POSTED

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

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outcome · POSTED

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

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outcome · POSTED

Time to Subsequent Systemic Cancer Treatments

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

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
healthy Volunteers: false
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
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.
intervention Names
Drug: Xevinapant
Drug: Cisplatin
Radiation: intensity-modulated radiation therapy (IMRT)
label
Xevinapant + Cisplatin + IMRT
type
EXPERIMENTAL

interventions

arm Group Labels
Xevinapant + Cisplatin + IMRT
description
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.
name
Xevinapant
other Names
Debio 1143
type
DRUG
arm Group Labels
Xevinapant + Cisplatin + IMRT
description
Participants will receive weekly cisplatin for 7 weeks on Cycle 1 Day 2 (C1D2), C1D9, C1D16, C2D2, C2D9, C2D16, and C3D2).
name
Cisplatin
type
DRUG
arm Group Labels
Xevinapant + Cisplatin + IMRT
description
Participants will receive 70 Gray (Gy) of IMRT in 35 fractions, 2 Gy/fraction, 5 days/week
name
intensity-modulated radiation therapy (IMRT)
type
RADIATION

Study design

allocation

intervention Model

SINGLE_GROUP

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 18
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

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

secondary Outcomes

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.
measure
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment-Related TEAEs
time Frame
Screening up to end of treatment (Day 134) and then follow up every 3 months (assessed up to maximum 6 months)
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.
measure
Absolute Estimated Glomerular Filtration Rate (eGFR) Values
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)
description
eGFR creatinine was evaluated using CKD-EPI formula. Absolute change from baseline in eGFR was presented.
measure
Absolute Change From Baseline in eGFR
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)
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.
measure
Objective Response (OR) According to Response Evaluation Criteria in Solid Tumor (RECIST) Version 1.1 Criteria as Assessed by Investigator
time Frame
Up to approximately 6 months
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.
measure
Progression Free Survival (PFS) According to RECIST Version 1.1 Criteria as Assessed by Investigator
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)
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.
measure
Locoregional Control (LRC) According to RECIST Version 1.1 Criteria As Assessed by Investigator
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
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).
measure
Time to Subsequent Systemic Cancer Treatments
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

Full study description

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.

Source references