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

Servier

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: Non-small Cell Lung Cancer (NSCLC)

Treatments: Drug: S095024 RDE; Drug: S095029 RDE; Drug: Cemiplimab; Drug: S095018 Recommended Dose Expansion (RDE); Drug: S095029; Drug: S095024; Drug: S095018

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT06162572

SPLFIO-174

Details and patient eligibility

About

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.

Enrollment: 176 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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
• Systemic chronic steroid therapy (>10mg/d prednisone or equivalent)
• Active infection, including infection requiring systemic antibiotic therapy
• 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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176 participants in 7 patient groups

S095018 (anti-TIM3 antibody) in combination with cemiplimab

Experimental group

Description:

Part A: Combination-therapy safety lead-in

Treatment:

Drug: S095018

Drug: Cemiplimab

S095024 (anti-CD73 antibody) in combination with cemiplimab

Experimental group

Description:

Part A: Combination-therapy safety lead-in

Treatment:

Drug: S095024

Drug: Cemiplimab

S095029 (anti-NKG2A antibody) in combination with cemiplimab

Experimental group

Description:

Part A: Combination-therapy safety lead-in

Treatment:

Drug: S095029

Drug: Cemiplimab

S095018 (anti-TIM3 antibody) RDE in combination with cemiplimab

Experimental group

Description:

Part B: Randomized dose expansion

Treatment:

Drug: S095018 Recommended Dose Expansion (RDE)

Drug: Cemiplimab

S095024 (anti-CD73 antibody) RDE in combination with cemiplimab

Experimental group

Description:

Part B: Randomized dose expansion

Treatment:

Drug: Cemiplimab

Drug: S095024 RDE

S095029 (anti-NKG2A antibody) RDE in combination with cemiplimab

Experimental group

Description:

Part B: Randomized dose expansion

Treatment:

Drug: Cemiplimab

Drug: S095029 RDE

Cemiplimab (control arm)

Active Comparator group

Description:

Part B: Randomized dose expansion

Treatment:

Drug: Cemiplimab