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

Phase 1TerminatedNCT06056310

EMD Serono Research & Development Institute, Inc.18 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Head and Neck Cancer

Interventions

XevinapantDRUG

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.

CisplatinDRUG

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

intensity-modulated radiation therapy (IMRT)RADIATION

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

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (23)

Mount Sinai Comprehensive Cancer Center

Miami Beach, Florida, United States

Outcomes

Primary Outcomes

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

Secondary Outcomes

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

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.

Time frame: 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

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.

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)

Data from ClinicalTrials.gov

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