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

Phase 1

Recruiting

• Conditions: Non-small Cell Lung Cancer (NSCLC)
• Interventions: Drug: S095018; Drug: S095024 RDE; Drug: S095024; Drug: S095029 RDE; Drug: S095029; Drug: S095018 Recommended Dose Expansion (RDE); Drug: Cemiplimab

• Registration Number: NCT06162572
• Lead Sponsor: Servier Bio-Innovation LLC

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-11-29
• Study First Submitted QC: 2023-12-07
• Study First Posted: 2023-12-08
• Study Start: 2024-08-07
• Status Verified: 2025-07
• Last Update Submitted: 2025-07-07
• Last Update Posted: 2025-07-08
• Primary Completion: 2027-04
• Study Completion: 2027-07-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 176

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)
• 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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
S095018 (anti-TIM3 antibody) in combination with cemiplimab	Cemiplimab	Part A: Combination-therapy safety lead-in
S095029 (anti-NKG2A antibody) RDE in combination with cemiplimab	Cemiplimab	Part B: Randomized dose expansion
S095024 (anti-CD73 antibody) RDE in combination with cemiplimab	Cemiplimab	Part B: Randomized dose expansion
S095018 (anti-TIM3 antibody) in combination with cemiplimab	S095018	Part A: Combination-therapy safety lead-in
S095024 (anti-CD73 antibody) in combination with cemiplimab	Cemiplimab	Part A: Combination-therapy safety lead-in
S095024 (anti-CD73 antibody) RDE in combination with cemiplimab	S095024 RDE	Part B: Randomized dose expansion
S095024 (anti-CD73 antibody) in combination with cemiplimab	S095024	Part A: Combination-therapy safety lead-in
S095029 (anti-NKG2A antibody) RDE in combination with cemiplimab	S095029 RDE	Part B: Randomized dose expansion
S095029 (anti-NKG2A antibody) in combination with cemiplimab	S095029	Part A: Combination-therapy safety lead-in
S095018 (anti-TIM3 antibody) RDE in combination with cemiplimab	S095018 Recommended Dose Expansion (RDE)	Part B: Randomized dose expansion
S095029 (anti-NKG2A antibody) in combination with cemiplimab	Cemiplimab	Part A: Combination-therapy safety lead-in
S095018 (anti-TIM3 antibody) RDE in combination with cemiplimab	Cemiplimab	Part B: Randomized dose expansion
Cemiplimab (control arm)	Cemiplimab	Part B: Randomized dose expansion

Primary Outcome Measures

Name	Time	Method
Adverse Events (AEs) Leading to Dose Interruption, Modification, or Delays	From signed ICF through treatment discontinuation (up to 108 weeks of treatment)	Part A
Incidence and severity of serious adverse events (SAEs)	From the signed ICF to 120 days after the last dose	Part A
Objective Response (OR)	Until study termination (approximately 2 years)	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.
Incidence and severity of dose-limiting toxicities (DLTs) during the first 2 cycles of combination treatment	Through the end of the Cycle 2 (each cycle is 21 days)	Part A
Incidence and severity of adverse events (AEs)	From the signed informed consent form (ICF) to 30 days after the last dose	Part A
Adverse Events (AEs) Leading to Permanent Treatment Discontinuation	From signed ICF through treatment discontinuation (up to 108 weeks of treatment)	Part A

Secondary Outcome Measures

Name	Time	Method
Objective Response (OR)	Until study termination (approximately 3 years)	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.
Plasma or serum concentration of S095024	From first dose to 30 days after the last dose	Part A and B
Duration of Response (DoR)	Until study termination (approximately 3 years)	Part A and B: The time from the first documentation of CR or PR until the documented progressive disease (PD) or death, as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and immune RECIST (iRECIST) as assessed by the investigator.
Disease Control (DC)	Until study termination (approximately 3 years)	Part A and B: Participants who achieved stable disease (SD), PR, or CR (based on participant's best response), as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and immune RECIST (iRECIST) as assessed by the investigator.
Incidence and titer of anti-drug antibodies (ADA) directed against S095018	From screening to 90 days after the last dose	Part A and B
Incidence and titer of anti-drug antibodies (ADA) directed against S095029	From screening to 90 days after the last dose	Part A and B
6-month Durable Response (6-month DR)	Until study termination (approximately 3 years)	Part A and B: Continuous CR or PR for ≥ 6 months, recorded between the date of the first dose of treatment and the date of the first objectively documented progression per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 or the date of subsequent anti-cancer therapy, whichever occurs first.
Incidence and titer of anti-drug antibodies (ADA) directed against S095024	From screening to 90 days after the last dose	Part A and B
Incidence and severity of adverse events (AEs)	From signed ICF to 30 days after the last dose	Part B
Incidence and severity of serious adverse events (SAEs)	From signed ICF to 120 days after the last dose	Part B
Adverse Events (AEs) Leading to Permanent Treatment Discontinuation	From signed ICF through treatment discontinuation (up to 108 weeks of treatment)	Part B
Best Overall Response (BOR)	Until study termination (approximately 3 years)	Part A and B: The best response designation using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and immune RECIST (iRECIST), recorded between the date of the first dose of treatment and the date of the first objectively documented progression or the date of subsequent anti-cancer therapy, whichever occurs first. CR or PR used in the BOR requires a confirmation that is at least 4 weeks apart.
Progression-Free Survival (PFS)	Until study termination (approximately 3 years)	Part A and B: The time from the first dose to the first documented PD or death due to any cause, whichever occurs first, as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and immune RECIST (iRECIST) as assessed by the investigator.
Plasma or serum concentration of S095018	From first dose to 30 days after the last dose	Part A and B
Plasma or serum concentration of S095029	From first dose to 30 days after the last dose	Part A and B
Adverse Events (AEs) Leading to Dose Interruption, Modification, or Delays	From signed ICF through treatment discontinuation (up to 108 weeks of treatment)	Part B

Trial Locations

Locations (73)

Loma Linda University; 🇺🇸 Loma Linda, California, United States

University of Kansas Medical Center; 🇺🇸 Lawrence, Kansas, United States

Henry Ford Health; 🇺🇸 Detroit, Michigan, United States

Comprehensive Cancer Center of Nevada; 🇺🇸 Las Vegas, Nevada, United States

Gabrail Cancer Center; 🇺🇸 Canton, Ohio, United States

Ohio State University Comprehensive Cancer Center; 🇺🇸 Columbus, Ohio, United States

Virginia Cancer Specialists, P.C.; 🇺🇸 Fairfax, Virginia, United States

Instituto Médico Especializado Alexander Fleming; 🇦🇷 Ciudad Autonoma de Buenos Aires, Argentina

Sanatorio Parque S.A.; 🇦🇷 Santa Fe, Argentina

Border Medical Oncology Research Unit; 🇦🇺 Albury, Australia

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