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

A Phase 1b/2, Multicenter, Open-label Platform Study of Select Immunotherapy Combinations in Adult Participants With Previously Untreated Advanced Non-small Cell Lung Cancer (NSCLC) With High PD-L1 Expression

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 Overview

• Status: Active, not recruiting
• Conditions: Non-small Cell Lung Cancer (NSCLC)
• Intervention / Treatment: Drug: S095018; Drug: Cemiplimab; Drug: S095024; Drug: S095029; Drug: S095018 Recommended Dose Expansion (RDE); Drug: S095024 RDE; Drug: S095029 RDE

• Study Type: Interventional
• Enrollment (Actual): 102
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina
    • Instituto Medico Especializado Alexander Fleming
  • Santa Fe, Argentina
    • Sanatorio Parque S.A.
• Australia
  • Albury, Australia, 2640
    • Border Medical Oncology Research Unit
  • Bedford Park, Australia, 5042
    • Flinders Medical Centre
  • St Albans, Australia, 3021
    • Sunshine Hospital
  • Traralgon, Australia, 3844
    • Latrobe Regional Health
• Austria
  • Linz, Austria, 4020
    • Ordensklinikum Linz Elisabethinen
  • Sankt Pölten, Austria, 3100
    • Universitatsklinikum St. Poelten
  • Vienna, Austria, 1090
    • Medical University of Vienna - Akh
• Belgium
  • Hasselt, Belgium, 3500
    • Jessa Ziekenhuis
  • Leuven, Belgium, 3500
    • Uz Leuven Campus Gasthuisberg
• Brazil
  • Barretos, Brazil, 14784-400
    • Hospital de Amor - Barretos
  • Chapecó, Brazil, 89812618
    • Supera Oncologia
  • Curitiba, Brazil, 80810-050
    • CIONC
  • Natal, Brazil, 59035-055
    • Liga Contra O Cancer - Natal
  • Porto Alegre, Brazil, 90020-090
    • Santa Casa de Porto Alegre
  • Porto Alegre, Brazil, 90619-900
    • Hospital Sao Lucas Da Pucrs
  • Rio de Janeiro, Brazil, 22250-905
    • Oncoclinicas Rj
  • São Paulo, Brazil, 01509-010
    • Hospital A C Camargo
  • São Paulo, Brazil, 03102-002
    • Hospital São Camilo
  • São Paulo, Brazil, 04538-132
    • Oncoclinicas Sp
  • São Paulo, Brazil, 05652-900
    • Hospital Albert Einstein
• France
  • Dijon, France, 21079
    • Centre Georges Francois Leclerc
  • Grenoble, France, 38043
    • Chu Grenoble Alpes
  • Marseille, France, 13009
    • Institut Paoli Calmette
  • Saint-Herblain, France, 44805
    • Centre René Gauducheau/Inst de Cancér. de L'Ouest
  • Villejuif, France, 94805
    • Institut Gustave Roussy
• Hong Kong
  • Hong Kong, Hong Kong
    • Queen Mary Hospital
  • Hong Kong, Hong Kong
    • Prince of Wales Hospital
  • Hong Kong, Hong Kong
    • Hong Kong United Onology Centre
• Hungary
  • Farkasgyepű, Hungary, 8582
    • Farkasgyepu Tudogyogyintezet
  • Gyöngyös, Hungary, 3200
    • Bugat Pal Hospital
  • Pécs, Hungary, 7624
    • Pecsi Tudomanyegyetem, Klinikai Kozpont
• Italy
  • Aviano, Italy, 33081
    • Centro di riferimento Oncologico
  • Meldola, Italy, 47014
    • Inst. Romagnolo Per Lo Studio E La Cura Dei Tumori
  • Milan, Italy, 20141
    • Istituto Europeo di Oncologia
  • Milan, Italy, 20162
    • ASST Grande Ospedale Metropolitano Niguarda
  • Milan, Italy, 20133
    • Irccs Fondazione Istituto Nazionale Dei Tumori
  • Naples, Italy, 80131
    • Ist. Nazionale Tumori Irccs Fondazione G Pascale
  • Perugia, Italy, 06132
    • Azienda Ospedaliera S. Maria Della Misericordia
  • Roma, Italy, 00144
    • Istituto Nazionale Tumori Regina Elena
  • Rozzano, Italy, 20089
    • Istituto Clinico Humanitas I.R.C.C.S
• Romania
  • Cluj-Napoca, Romania
    • Inst Oncologic "Prof Dr I Chiricuta" Cluj Napoca
  • Ploieşti, Romania
    • Ploiesti Municipal Hospital
• Spain
  • Barcelona, Spain, 08035
    • Vall D' Hebron Institute of Oncology (Vhio), University Hospital
  • Madrid, Spain, 28007
    • Hospital General Universitario Gregorio Marañón
  • Madrid, Spain, 28027
    • Clinica Universitaria de Navarra (Madrid)
  • Madrid, Spain, 28050
    • Hospital Univ. Hm Sanchinarro Start Ciocc Early Phase
  • Málaga, Spain, 29010
    • Hospital Universitario Virgen de la Victoria
  • Pamplona, Spain, 31008
    • Clinica Universitaria de Navarra (Pamplona)
  • Seville, Spain, 41013
    • Hospital Virgen del Rocío
  • Valencia, Spain, 46026
    • Hospital Universitario y Politécnico La FE
• Taiwan
  • Taipei, Taiwan, 100225
    • National Taiwan University Hospital
  • Taipei, Taiwan, 114202
    • Tri-Service General Hospital
• United Kingdom
  • London, United Kingdom, SW3 6JJ
    • The Royal Marsden in Chelsea
  • London, United Kingdom, SM2 5PT
    • The Royal Marsden in Sutton
  • Manchester, United Kingdom, M20 4BX
    • The Christie Nhs Foundation Foundation Trust
• United States
  • California
    • Loma Linda, California, United States, 92354
      • Loma Linda University
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health
  • Nevada
    • Las Vegas, Nevada, United States, 89119
      • Comprehensive Cancer Center of Nevada
  • Ohio
    • Canton, Ohio, United States, 44718
      • Gabrail Cancer Center
    • Columbus, Ohio, United States, 43210
      • Ohio State University Comprehensive Cancer Center
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Virginia Cancer Specialists, P.C.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: S095018 (anti-TIM3 antibody) in combination with cemiplimab; Part A: Combination-therapy safety lead-in	Drug: S095018; Via IV infusion on Day 1 of each 21-day cycle; Drug: Cemiplimab; 350 mg via IV infusion on Day 1 of each 21-day cycle
Experimental: S095024 (anti-CD73 antibody) in combination with cemiplimab; Part A: Combination-therapy safety lead-in	Drug: Cemiplimab; 350 mg via IV infusion on Day 1 of each 21-day cycle; Drug: S095024; Via IV infusion on Day 1 of each 21-day cycle
Experimental: S095029 (anti-NKG2A antibody) in combination with cemiplimab; Part A: Combination-therapy safety lead-in	Drug: Cemiplimab; 350 mg via IV infusion on Day 1 of each 21-day cycle; Drug: S095029; Via IV infusion on Day 1 of each 21-day cycle
Experimental: S095018 (anti-TIM3 antibody) RDE in combination with cemiplimab; Part B: Randomized dose expansion	Drug: Cemiplimab; 350 mg via IV infusion on Day 1 of each 21-day cycle; Drug: S095018 Recommended Dose Expansion (RDE); Via IV infusion on Day 1 of each 21-day cycle
Experimental: S095024 (anti-CD73 antibody) RDE in combination with cemiplimab; Part B: Randomized dose expansion	Drug: Cemiplimab; 350 mg via IV infusion on Day 1 of each 21-day cycle; Drug: S095024 RDE; Via IV infusion on Day 1 of each 21-day cycle
Experimental: S095029 (anti-NKG2A antibody) RDE in combination with cemiplimab; Part B: Randomized dose expansion	Drug: Cemiplimab; 350 mg via IV infusion on Day 1 of each 21-day cycle; Drug: S095029 RDE; Via IV infusion on Day 1 of each 21-day cycle
Active Comparator: Cemiplimab (control arm); Part B: Randomized dose expansion	Drug: Cemiplimab; 350 mg via IV infusion on Day 1 of each 21-day cycle

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Until study termination (approximately 3 years)
Best Overall Response (BOR)	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.	Until study termination (approximately 3 years)
Duration of Response (DoR)	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.	Until study termination (approximately 3 years)
Disease Control (DC)	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.	Until study termination (approximately 3 years)
6-month Durable Response (6-month DR)	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.	Until study termination (approximately 3 years)
Progression-Free Survival (PFS)	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.	Until study termination (approximately 3 years)
Plasma or serum concentration of S095018	Part A and B	From first dose to 30 days after the last dose
Plasma or serum concentration of S095024	Part A and B	From first dose to 30 days after the last dose
Plasma or serum concentration of S095029	Part A and B	From first dose to 30 days after the last dose
Incidence and titer of anti-drug antibodies (ADA) directed against S095018	Part A and B	From screening to 90 days after the last dose
Incidence and titer of anti-drug antibodies (ADA) directed against S095024	Part A and B	From screening to 90 days after the last dose
Incidence and titer of anti-drug antibodies (ADA) directed against S095029	Part A and B	From screening to 90 days after the last dose
Incidence and severity of adverse events (AEs)	Part B	From signed ICF to 30 days after the last dose
Incidence and severity of serious adverse events (SAEs)	Part B	From signed ICF to 120 days after the last dose
Adverse Events (AEs) Leading to Dose Interruption, Modification, or Delays	Part B	From signed ICF through treatment discontinuation (up to 108 weeks of treatment)
Adverse Events (AEs) Leading to Permanent Treatment Discontinuation	Part B	From signed ICF through treatment discontinuation (up to 108 weeks of treatment)

Collaborators and Investigators

• Sponsor: Servier Bio-Innovation LLC
• Collaborators: Regeneron Pharmaceuticals; Institut de Recherches Internationales Servier

Study record dates

Study Major Dates

• Study Start (Actual): August 7, 2024
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): July 1, 2027

Study Registration Dates

• First Submitted: November 29, 2023
• First Submitted That Met QC Criteria: December 7, 2023
• First Posted (Actual): December 8, 2023

Study Record Updates

• Last Update Posted (Actual): May 11, 2026
• Last Update Submitted That Met QC Criteria: May 8, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Non-small Cell Lung Carcinoma
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carcinoma, Non-Small-Cell Lung; Antineoplastic Agents, Immunological; Antineoplastic Agents; cemiplimab
• Other Study ID Numbers: SPLFIO-174

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Qualified scientific and medical researchers can request access to anonymized patient-level and study-level clinical trial data.

Access can be requested for all interventional clinical studies:

• used for Marketing Authorization (MA) of medicines and new indications approved after 1 January 2014 in the European Economic Area (EEA) or the United States (US).
• where Servier is the Marketing Authorization Holder (MAH). The date of the first MA of the new medicine (or the new indication) in one of the EEA Member States will be considered for this scope.

In addition, access can be requested for all interventional clinical studies in patients:

• sponsored by Servier
• with a first patient enrolled as of 1 January 2004 onwards
• for New Chemical Entity or New Biological Entity (new pharmaceutical form excluded) for which development has been terminated before any Marketing authorization (MA) approval.

• IPD Sharing Time Frame: After Marketing Authorization in EEA or US if the study is used for the approval.
• IPD Sharing Access Criteria: Researchers should register on Servier Data Portal and fill in the research proposal form. This form in four parts should be fully documented. The Research Proposal Form will not be reviewed until all mandatory fields are completed.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No