Phase 1b/2 Platform Study of Select Immunotherapy Combinations in Participants With Advanced Non-small Cell Lung Cancer (NSCLC)

Phase 2Active Not RecruitingNCT06162572

Servier Bio-Innovation LLC102 enrolled

Overview

This is a Phase 1b/2 study evaluating the anti-PD1 antibody, cemiplimab, in combination with either S095018 (anti-TIM3 antibody), S095024 (anti-CD73 antibody), or S095029 (anti-NKG2A antibody) in adult participants with previously untreated advanced/metastatic non-small cell lung cancer (NSCLC) with high PD-L1 expression. The study includes two parts: part A, the combination-therapy safety lead-in phase to determine the recommended dose for expansion (RDE) for S095018, S095024, and S095029 in combination with cemiplimab and part B, the randomized dose expansion phase to assess the efficacy of S095018, S095024, or S095029 in combination with cemiplimab. Study treatment will be administered for a maximum of 108 weeks, or until confirmed disease progression per iRECIST and/ or until meeting other treatment discontinuation criteria.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

102

Conditions

Non-small Cell Lung Cancer (NSCLC)

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Adult patient aged ≥ 18 years * Written informed consent * Histologically (squamous or non-squamous) or cytologically documented locally advanced NSCLC not eligible for surgical resection and/or definitive chemoradiation, or metastatic NSCLC * No prior systemic treatment for locally advanced or metastatic NSCLC * High tumor cell PD-L1 expression \[Tumor Proportion Score (TPS) ≥50%\] based on documented status as determined by an approved test * Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 * Measurable disease as determined by RECIST v1.1 Exclusion Criteria: * Tumors harboring driver mutations/genetic aberrations for which targeted therapies are approved as frontline treatment (e.g. EGFR mutation, ALK fusion oncogene, ROS1 aberrations) * Prior immune checkpoint inhibitor therapy * Active brain metastases * Participants with active and uncontrolled hepatitis B virus (HBV) or hepatitis C virus (HCV) infection * Uncontrolled HIV infection. Participants with HIV who have controlled infection (undetectable viral load and CD4 count above 350 either spontaneously or on a stable antiviral regimen) are allowed to enroll * Active, known or suspected autoimmune disease or immune deficiency * History of hypersensitivity reactions to any ingredient of the investigational medicinal product (IMP) and other monoclonal antibody (mAbs) and/or their excipients * History of interstitial lung disease, idiopathic pulmonary fibrosis, drug-induced pneumonitis, idiopathic pneumonitis or active pneumonitis ≥ grade 2 * History of inflammatory bowel disease or colitis ≥ grade 2 * History of hemophagocytic lymphohistiocytosis. * Systemic chronic steroid therapy (\>10mg/d prednisone or equivalent) * Clinically significant infection, as assessed by the investigator * Pregnant or breast-feeding (lactating) women * Participants with a history of allogeneic organ transplantation (e.g., stem cell or solid organ transplant) * Any medical condition that would in the investigator's judgement prevent the participant's participation in the clinical study

Outcomes

Primary Outcomes

Incidence and severity of dose-limiting toxicities (DLTs) during the first 2 cycles of combination treatment

Part A

Time frame: Through the end of the Cycle 2 (each cycle is 21 days)

Incidence and severity of adverse events (AEs)

Part A

Time frame: From the signed informed consent form (ICF) to 30 days after the last dose

Incidence and severity of serious adverse events (SAEs)

Part A

Time frame: From the signed ICF to 120 days after the last dose

Adverse Events (AEs) Leading to Dose Interruption, Modification, or Delays

Part A

Time frame: From signed ICF through treatment discontinuation (up to 108 weeks of treatment)

Adverse Events (AEs) Leading to Permanent Treatment Discontinuation

Part A

Time frame: From signed ICF through treatment discontinuation (up to 108 weeks of treatment)

Objective Response (OR)

Part B: Participants who achieve complete response (CR) or partial response (PR), as per investigator assessment using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.

Time frame: Until study termination (approximately 2 years)

Secondary Outcomes

Objective Response (OR)

Part A: Participants who achieve CR or PR, as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and immune RECIST (iRECIST) as assessed by the investigator.