A Phase 3 Study to Evaluate Petosemtamab Compared With Investigator's Choice Monotherapy in Previously Treated Head and Neck Squamous Cell Carcinoma Patients (LiGeR-HN2)

Phase 3Active Not RecruitingNCT06496178

Merus B.V.621 enrolled

Overview

This is a phase 3 open-label, randomized, controlled, multicenter study to compare petosemtamab vs investigator's choice monotherapy in HNSCC patients for the second- and third-line treatment of incurable metastatic/recurrent disease. HNSCC patients must have progressive disease (PD) on or after anti-PD-1 therapy and platinum-containing therapy. Patients treated with platinum-containing therapy only in the adjuvant setting, or in the context of multimodal therapy for locally advanced disease, should have PD within 6 months of the last dose of platinum-containing therapy.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

621

Conditions

Head and Neck Squamous Cell Carcinoma

Interventions

PetosemtamabDRUG

MCLA-158

Investigator's ChoiceDRUG

Cetuximab

Investigator's ChoiceDRUG

Methotrexate

Investigator's Choice

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Signed ICF before initiation of any study procedures. * Age ≥ 18 years at signing of ICF. * Histologically previously confirmed HNSCC with evidence of metastatic or locally advanced disease not amenable to standard therapy with curative intent. * HNSCC participants progressed on or after anti-PD-1 therapy and platinum-containing therapy. * The eligible HNSCC primary tumor locations are oropharynx, oral cavity, hypopharynx, and larynx. * A baseline new tumor sample unless the participant has an available tumor sample as an FFPE block with sufficient material. * Measurable disease as defined by RECIST v1.1 by radiologic methods. * ECOG PS of 0 or 1 * Life expectancy ≥ 12 weeks, as per investigator * Adequate organ function (as per protocol) Exclusion Criteria: * Central nervous system metastases that are untreated or symptomatic, or require radiation, surgery, or continued steroid therapy to control symptoms within 14 days prior to randomization. * Known leptomeningeal involvement * Any systemic anticancer therapy within 4 weeks prior to randomization. * Major surgery within 3 weeks or palliative radiotherapy within 2 weeks prior to randomization. * Persistent Grade \>1 clinically significant toxicities related to prior antineoplastic therapies * History of hypersensitivity reaction to any of the excipients of treatment required for this study. * Unstable angina; history of congestive heart failure of Class II-IV New York Heart Association (NYHA) criteria, or serious cardiac arrhythmia requiring treatment or history of myocardial infarction within 6 months of study entry * History of prior malignancies with the exception of localized cancer with curative resection (e.g. cervical intraepithelial neoplasia or nonmelanoma skin cancer) * Current dyspnea at rest of any origin, or other diseases requiring continuous oxygen therapy * Current serious illness or medical conditions including, but not limited to, uncontrolled active infection, clinically significant pulmonary, metabolic or psychiatric disorders * Participants with known infectious diseases (as per protocol) * Pregnant or breastfeeding participants

Locations (197)

Outcomes

Primary Outcomes

Overall Survival (OS)

OS was defined as the time from randomization to death due to any cause.

Time frame: Up to approximately 3 years

Secondary Outcomes

Objective Response Rate (ORR) as Assessed by Blinded Independent Central Review

ORR was defined as the proportion of participants in the analysis population who had a Complete Response or Partial Response based per RECIST v1.1 with confirmation.