Phase 1b/2 Platform Study of Select Immunotherapy Combinations in Participants With Advanced Non-small Cell Lung Cancer (NSCLC)
- Conditions
- Non-small Cell Lung Cancer (NSCLC)
- Interventions
- Drug: S095024 RDEDrug: S095029 RDEDrug: S095018 Recommended Dose Expansion (RDE)
- 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
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 176
- 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
- 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
Adverse Events (AEs) Leading to Dose Interruption, Modification, or Delays From signed ICF through treatment discontinuation (up to 108 weeks of treatment) Part 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
Trial Locations
- Locations (144)
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
Flinders Medical Centre
🇦🇺Bedford Park, Australia
Sunshine Hospital
🇦🇺St Albans, Australia
Latrobe Regional Health
🇦🇺Traralgon, Australia
Medical University of Vienna - Akh
🇦🇹Wien, Austria
Jessa Ziekenhuis
🇧🇪Hasselt, Belgium
Uz Leuven Campus Gasthuisberg
🇧🇪Leuven, Belgium
Hospital de Amor - Barretos
🇧🇷Barretos, Brazil
Supera Oncologia
🇧🇷Chapecó, Brazil
CIONC
🇧🇷Curitiba, Brazil
ONCOSITE
🇧🇷Ijuí, Brazil
Liga Contra O Cancer - Natal
🇧🇷Natal, Brazil
Santa Casa de Porto Alegre
🇧🇷Porto Alegre, Brazil
Hospital São Lucas Da Pucrs
🇧🇷Porto Alegre, Brazil
Oncoclinicas Rj
🇧🇷Rio De Janeiro, Brazil
Icesp - Instituto Do Câncer Do Estado de São Paulo
🇧🇷São Paulo, Brazil
Hospital A C Camargo
🇧🇷São Paulo, Brazil
Hospital São Camilo
🇧🇷São Paulo, Brazil
Oncoclinicas Sp
🇧🇷São Paulo, Brazil
Hospital Albert Einstein
🇧🇷São Paulo, Brazil
Centre Georges Francois Leclerc
🇫🇷Dijon, France
Chu Grenoble Alpes
🇫🇷Grenoble, France
Institut Paoli Calmette
🇫🇷Marseille, France
Centre René Gauducheau/Inst de Cancér. de L'Ouest
🇫🇷Saint-Herblain, France
Institut Gustave Roussy
🇫🇷Villejuif, France
Hong Kong United Onology Centre
🇭🇰Hong Kong, Hong Kong
Prince of Wales Hospital
🇭🇰Hong Kong, Hong Kong
Queen Mary Hospital
🇭🇰Hong Kong, Hong Kong
Farkasgyepu Tudogyogyintezet
🇭🇺Farkasgyepű, Hungary
Bugat Pal Hospital
🇭🇺Gyöngyös, Hungary
Pecsi Tudomanyegyetem, Klinikai Kozpont
🇭🇺Pécs, Hungary
Centro Di Riferimento Oncologico
🇮🇹Aviano, Italy
Inst. Romagnolo Per Lo Studio E La Cura Dei Tumori
🇮🇹Meldola, Italy
Irccs Fondazione Istituto Nazionale Dei Tumori
🇮🇹Milano, Italy
Istituto Europeo Di Oncologia
🇮🇹Milano, Italy
ASST Grande Ospedale Metropolitano Niguarda
🇮🇹Milano, Italy
Ist. Nazionale Tumori Irccs Fondazione G Pascale
🇮🇹Napoli, Italy
Azienda Ospedaliera S. Maria Della Misericordia
🇮🇹Perugia, Italy
Istituto Clinico Humanitas I.R.C.C.S
🇮🇹Rozzano, Italy
Pusan National University Hospital
🇰🇷Busan, Korea, Republic of
Gacheon University Gil Medical Center
🇰🇷Incheon, Korea, Republic of
Korea University Guro Hospital
🇰🇷Seoul, Korea, Republic of
Centrul de Oncologie Sf Nectarie
🇷🇴Craiova, Romania
Val de Hebron Institute of Oncology (Vhio), University Hospital
🇪🇸Barcelona, Spain
National Taiwan University Hospital
🇨🇳Taipei, Taiwan
Istituto Nazionale Tumori Regina Elena
🇮🇹Roma, Italy
Chungbuk National University Hospital
🇰🇷Cheongju-si, Korea, Republic of
Inst Oncologic "Prof Dr I Chiricuta" Cluj Napoca
🇷🇴Cluj-Napoca, Romania
Centrul de Radioterapie Amethyst
🇷🇴Otopeni, Romania
Ploiesti Municipal Hospital
🇷🇴Ploieşti, Romania
Hospital Univ. Hm Sanchinarro Start Ciocc Early Phase
🇪🇸Madrid, Spain
Hospital Universitario Virgen de La Victoria
🇪🇸Málaga, Spain
Hospital Universitario Y Politecnico La Fe
🇪🇸Valencia, Spain
Hospital General Universitario Gregorio Marañón
🇪🇸Madrid, Spain
Clinica Universitaria de Navarra (Madrid)
🇪🇸Madrid, Spain
Clinica Universitaria de Navarra (Pamplona)
🇪🇸Pamplona, Spain
Hospital Virgen Del Rocío
🇪🇸Sevilla, Spain
Tri-Service General Hospital
🇨🇳Taipei, Taiwan
The Royal Marsden in Sutton
🇬🇧London, United Kingdom
The Royal Marsden in Chelsea
🇬🇧London, United Kingdom
Imperial College London
🇬🇧London, United Kingdom
The Christie Nhs Foundation Foundation Trust
🇬🇧Manchester, United Kingdom
Clinica Universitaria de Navarra (Madrid)
🇪🇸Madrid, Spain
Hospital Univ. Hm Sanchinarro Start Ciocc Early Phase
🇪🇸Madrid, Spain
Hospital Universitario Virgen de La Victoria
🇪🇸Málaga, Spain
Clinica Universitaria de Navarra (Pamplona)
🇪🇸Pamplona, Spain
Hospital Virgen Del Rocío
🇪🇸Sevilla, Spain
Hospital Universitario Y Politecnico La Fe
🇪🇸Valencia, Spain
National Taiwan University Hospital
🇨🇳Taipei, Taiwan
Tri-Service General Hospital
🇨🇳Taipei, Taiwan
The Royal Marsden in Sutton
🇬🇧London, United Kingdom
The Royal Marsden in Chelsea
🇬🇧London, United Kingdom
Imperial College London
🇬🇧London, United Kingdom
The Christie Nhs Foundation Foundation Trust
🇬🇧Manchester, United Kingdom
Institut Paoli Calmette
🇫🇷Marseille, France
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
Flinders Medical Centre
🇦🇺Bedford Park, Australia
Sunshine Hospital
🇦🇺St Albans, Australia
Latrobe Regional Health
🇦🇺Traralgon, Australia
Ordensklinikum Linz Elisabethinen
🇦🇹Linz, Austria
Universitatsklinikum St. Poelten
🇦🇹St. Poelten, Austria
Medical University of Vienna - Akh
🇦🇹Wien, Austria
Jessa Ziekenhuis
🇧🇪Hasselt, Belgium
Uz Leuven Campus Gasthuisberg
🇧🇪Leuven, Belgium
Hospital de Amor - Barretos
🇧🇷Barretos, Brazil
Supera Oncologia
🇧🇷Chapecó, Brazil
CIONC
🇧🇷Curitiba, Brazil
ONCOSITE
🇧🇷Ijuí, Brazil
Liga Contra O Cancer - Natal
🇧🇷Natal, Brazil
Santa Casa de Porto Alegre
🇧🇷Porto Alegre, Brazil
Hospital São Lucas Da Pucrs
🇧🇷Porto Alegre, Brazil
Oncoclinicas Rj
🇧🇷Rio De Janeiro, Brazil
Icesp - Instituto Do Câncer Do Estado de São Paulo
🇧🇷São Paulo, Brazil
Hospital A C Camargo
🇧🇷São Paulo, Brazil
Hospital São Camilo
🇧🇷São Paulo, Brazil
Oncoclinicas Sp
🇧🇷São Paulo, Brazil
Hospital Albert Einstein
🇧🇷São Paulo, Brazil
Centre Georges Francois Leclerc
🇫🇷Dijon, France
Chu Grenoble Alpes
🇫🇷Grenoble, France
Centre René Gauducheau/Inst de Cancér. de L'Ouest
🇫🇷Saint-Herblain, France
Institut Gustave Roussy
🇫🇷Villejuif, France
Hong Kong United Onology Centre
🇭🇰Hong Kong, Hong Kong
Prince of Wales Hospital
🇭🇰Hong Kong, Hong Kong
Queen Mary Hospital
🇭🇰Hong Kong, Hong Kong
Farkasgyepu Tudogyogyintezet
🇭🇺Farkasgyepű, Hungary
Bugat Pal Hospital
🇭🇺Gyöngyös, Hungary
Pecsi Tudomanyegyetem, Klinikai Kozpont
🇭🇺Pécs, Hungary
Centro Di Riferimento Oncologico
🇮🇹Aviano, Italy
Inst. Romagnolo Per Lo Studio E La Cura Dei Tumori
🇮🇹Meldola, Italy
Irccs Fondazione Istituto Nazionale Dei Tumori
🇮🇹Milano, Italy
Istituto Europeo Di Oncologia
🇮🇹Milano, Italy
ASST Grande Ospedale Metropolitano Niguarda
🇮🇹Milano, Italy
Ist. Nazionale Tumori Irccs Fondazione G Pascale
🇮🇹Napoli, Italy
Azienda Ospedaliera S. Maria Della Misericordia
🇮🇹Perugia, Italy
Istituto Nazionale Tumori Regina Elena
🇮🇹Roma, Italy
Istituto Clinico Humanitas I.R.C.C.S
🇮🇹Rozzano, Italy
Pusan National University Hospital
🇰🇷Busan, Korea, Republic of
Chungbuk National University Hospital
🇰🇷Cheongju-si, Korea, Republic of
Gacheon University Gil Medical Center
🇰🇷Incheon, Korea, Republic of
Korea University Guro Hospital
🇰🇷Seoul, Korea, Republic of
Inst Oncologic "Prof Dr I Chiricuta" Cluj Napoca
🇷🇴Cluj-Napoca, Romania
Centrul de Oncologie Sf Nectarie
🇷🇴Craiova, Romania
Centrul de Radioterapie Amethyst
🇷🇴Otopeni, Romania
Ploiesti Municipal Hospital
🇷🇴Ploieşti, Romania
Val de Hebron Institute of Oncology (Vhio), University Hospital
🇪🇸Barcelona, Spain
Hospital General Universitario Gregorio Marañón
🇪🇸Madrid, Spain