A Study of Xevinapant (Debio 1143) in Combination With Platinum-Based Chemotherapy and Standard Fractionation Intensity-Modulated Radiotherapy in Participants With Locally Advanced Squamous Cell Carcinoma of the Head and Neck, Suitable for Definitive Chemoradiotherapy (TrilynX)

Merck KGaA (EMD Serono)

Status and phase: Active, not recruiting; Phase 3

Conditions: Squamous Cell Carcinoma of the Head and Neck

Treatments: Drug: Placebo; Drug: Xevinapant (Debio 1143); Radiation: Intensity Modulation Radiation Therapy (IMRT); Drug: Cisplatin

Study type: Interventional

Funder types: Industry; Other

Identifiers

NCT04459715

Debio 1143-SCCHN-301

2020-000377-25 (EudraCT Number)

MS202359_0006

Details and patient eligibility

About

The primary objective of the study is to demonstrate superior efficacy of Xevinapant (Debio 1143) vs placebo when added to chemoradiotherapy (CRT) in locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN).

Enrollment: 730 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Eastern Cooperative Oncology Group performance status (ECOG PS) 0 or 1
• Histologically confirmed diagnosis of previously untreated Locally Advanced Squamous Cell Carcinoma of the Head and Neck (LA-SCCHN) participant (stage III, IVa or IVb according to the American Joint Committee on Cancer(AJCC))/Classification of malignant tumors: T=size of the primary tumor, N=regional lymph node involvement, M=distant metastasis (TNM) Staging System, 8th Edition.) suitable for definitive ChemoRadiotherapy (CRT), of at least one of the following sites: oropharynx, hypopharynx and larynx
• For OroPharyngeal Cancer (OPC) participants, primary tumors must be human papillomavirus (HPV)-negative as determined by p16 expression using immunohistochemistry
• Evaluable tumor burden (measurable and/or non-measurable tumor lesions) assessed by computed tomography scan (CT-scan) or magnetic resonance imaging (MRI), based on Response evaluation criteria in solid tumors (RECIST) version 1.1
• Peripheral neuropathy less than (<) grade 2
• Adequate hematologic, renal and hepatic function
• Other protocol defined inclusion criteria may apply

Exclusion criteria

• Primary tumor of nasopharynx, 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 Ed.)
• Prior definitive or adjuvant Radiotherapy (RT) and/or radical surgery to the head and neck region which may jeopardize the primary tumor irradiation plan, or any other prior SCCHN systemic treatment, including investigational agents
• Documented weight loss of >10% during the last 4 weeks prior to randomization (unless adequate measures are undertaken for nutritional support), OR plasmatic albumin < 3.0 g/dL. No albumin transfusions are allowed within 2 weeks before randomization
• Known allergy to Xevinapant (Debio 1143), cisplatin, carboplatin, other platinum-based agent or any excipient known to be present in any of these products or in the placebo formulation
• other protocol defined exclusion criteria may apply

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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730 participants in 2 patient groups

Xevinapant (Debio 1143)

Experimental group

Description:

Participants will receive: Concomitant chemo-radiation therapy period (Cycles 1-3): * Radiotherapy * Cisplatin * Xevinapant (Debio 1143) Monotherapy period (Cycles 4-6): • Xevinapant (Debio 1143)

Treatment:

Drug: Cisplatin

Radiation: Intensity Modulation Radiation Therapy (IMRT)

Drug: Xevinapant (Debio 1143)

Placebo

Active Comparator group

Description:

Participants will receive: Concomitant chemo-radiation therapy period (Cycles 1-3): * Radiotherapy * Cisplatin * Matched placebo Monotherapy period (Cycles 4-6): • Matched placebo

Treatment:

Drug: Cisplatin

Radiation: Intensity Modulation Radiation Therapy (IMRT)

Drug: Placebo