Clinical trial NCT06162572: Phase 1b/2 Platform Study of Select Immunotherapy Combinations in Participants With Advanced Non-small Cell Lung Cancer (NSCLC)
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Non-small Cell Lung Cancer (NSCLC)
Keywords: Non-small Cell Lung Carcinoma
Lead sponsor: Servier
Sponsor class: INDUSTRY
Collaborators: name: Institut de Recherches Internationales Servier
name: Regeneron Pharmaceuticals
First posted: 2023-12-08
Enrollment: 176
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Incidence and severity of dose-limiting toxicities (DLTs) during the first 2 cycles of combination treatment
timeFrame: Through the end of the Cycle 2 (each cycle is 21 days)
measure: Incidence and severity of adverse events (AEs)
timeFrame: From the signed informed consent form (ICF) to 30 days after the last dose
measure: Incidence and severity of serious adverse events (SAEs)
timeFrame: From the signed ICF to 120 days after the last dose
measure: Adverse Events (AEs) Leading to Dose Interruption, Modification, or Delays
timeFrame: From signed ICF through treatment discontinuation (up to 108 weeks of treatment)
measure: Adverse Events (AEs) Leading to Permanent Treatment Discontinuation
timeFrame: From signed ICF through treatment discontinuation (up to 108 weeks of treatment)
measure: Objective Response (OR)
timeFrame: Until study termination (approximately 2 years)
Secondary outcomes:
measure: Objective Response (OR)
timeFrame: Until study termination (approximately 3 years)
measure: Best Overall Response (BOR)
timeFrame: Until study termination (approximately 3 years)
measure: Duration of Response (DoR)
timeFrame: Until study termination (approximately 3 years)
measure: Disease Control (DC)
timeFrame: Until study termination (approximately 3 years)
measure: 6-month Durable Response (6-month DR)
timeFrame: Until study termination (approximately 3 years)
measure: Progression-Free Survival (PFS)
timeFrame: Until study termination (approximately 3 years)
measure: Plasma or serum concentration of S095018
timeFrame: From first dose to 30 days after the last dose
measure: Plasma or serum concentration of S095024
timeFrame: From first dose to 30 days after the last dose
measure: Plasma or serum concentration of S095029
timeFrame: From first dose to 30 days after the last dose
measure: Incidence and titer of anti-drug antibodies (ADA) directed against S095018
timeFrame: From screening to 90 days after the last dose
measure: Incidence and titer of anti-drug antibodies (ADA) directed against S095024
timeFrame: From screening to 90 days after the last dose
measure: Incidence and titer of anti-drug antibodies (ADA) directed against S095029
timeFrame: From screening to 90 days after the last dose
measure: Incidence and severity of adverse events (AEs)
timeFrame: From signed ICF to 30 days after the last dose
measure: Incidence and severity of serious adverse events (SAEs)
timeFrame: From signed ICF to 120 days after the last dose
measure: Adverse Events (AEs) Leading to Dose Interruption, Modification, or Delays
timeFrame: From signed ICF through treatment discontinuation (up to 108 weeks of treatment)
measure: Adverse Events (AEs) Leading to Permanent Treatment Discontinuation
timeFrame: From signed ICF through treatment discontinuation (up to 108 weeks of treatment)
Other outcomes:
Locations:
city: Loma Linda
country: United States
facility: Loma Linda University
state: California
city: Lawrence
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Detroit
country: United States
facility: Henry Ford Health
state: Michigan
city: Las Vegas
country: United States
facility: Comprehensive Cancer Center of Nevada
state: Nevada
city: Canton
country: United States
facility: Gabrail Cancer Center
state: Ohio
city: Columbus
country: United States
facility: Ohio State University Comprehensive Cancer Center
state: Ohio
city: Fairfax
country: United States
facility: Virginia Cancer Specialists, P.C.
state: Virginia
city: Ciudad Autonoma de Buenos Aires
country: Argentina
facility: Instituto Médico Especializado Alexander Fleming
city: Santa Fe
country: Argentina
facility: Sanatorio Parque S.A.
city: Albury
country: Australia
facility: Border Medical Oncology Research Unit
city: Bedford Park
country: Australia
facility: Flinders Medical Centre
city: St Albans
country: Australia
facility: Sunshine Hospital
city: Traralgon
country: Australia
facility: Latrobe Regional Health
city: Linz
country: Austria
facility: Ordensklinikum Linz Elisabethinen
city: St. Poelten
country: Austria
facility: Universitatsklinikum St. Poelten
city: Wien
country: Austria
facility: Medical University of Vienna - Akh
city: Hasselt
country: Belgium
facility: Jessa Ziekenhuis
city: Leuven
country: Belgium
facility: Uz Leuven Campus Gasthuisberg
city: Barretos
country: Brazil
facility: Hospital de Amor - Barretos
city: Chapecó
country: Brazil
facility: Supera Oncologia
city: Curitiba
country: Brazil
facility: CIONC
city: Ijuí
country: Brazil
facility: ONCOSITE
city: Natal
country: Brazil
facility: Liga Contra O Cancer - Natal
city: Porto Alegre
country: Brazil
facility: Santa Casa de Porto Alegre
city: Porto Alegre
country: Brazil
facility: Hospital São Lucas Da Pucrs
city: Rio De Janeiro
country: Brazil
facility: Oncoclinicas Rj
city: São Paulo
country: Brazil
facility: Icesp - Instituto Do Câncer Do Estado de São Paulo
city: São Paulo
country: Brazil
facility: Hospital A C Camargo
city: São Paulo
country: Brazil
facility: Hospital São Camilo
city: São Paulo
country: Brazil
facility: Oncoclinicas Sp
city: São Paulo
country: Brazil
facility: Hospital Albert Einstein
city: Dijon
country: France
facility: Centre Georges Francois Leclerc
city: Grenoble
country: France
facility: Chu Grenoble Alpes
city: Marseille
country: France
facility: Institut Paoli Calmette
city: Saint-Herblain
country: France
facility: Centre René Gauducheau/Inst de Cancér. de L'Ouest
city: Villejuif
country: France
facility: Institut Gustave Roussy
city: Hong Kong
country: Hong Kong
facility: Hong Kong United Onology Centre
city: Hong Kong
country: Hong Kong
facility: Prince of Wales Hospital
city: Hong Kong
country: Hong Kong
facility: Queen Mary Hospital
city: Farkasgyepű
country: Hungary
facility: Farkasgyepu Tudogyogyintezet
city: Gyöngyös
country: Hungary
facility: Bugat Pal Hospital
city: Pécs
country: Hungary
facility: Pecsi Tudomanyegyetem, Klinikai Kozpont
city: Aviano
country: Italy
facility: Centro Di Riferimento Oncologico
city: Meldola
country: Italy
facility: Inst. Romagnolo Per Lo Studio E La Cura Dei Tumori
city: Milano
country: Italy
facility: Irccs Fondazione Istituto Nazionale Dei Tumori
city: Milano
country: Italy
facility: Istituto Europeo Di Oncologia
city: Milano
country: Italy
facility: ASST Grande Ospedale Metropolitano Niguarda
city: Napoli
country: Italy
facility: Ist. Nazionale Tumori Irccs Fondazione G Pascale
city: Perugia
country: Italy
facility: Azienda Ospedaliera S. Maria Della Misericordia
city: Roma
country: Italy
facility: Istituto Nazionale Tumori Regina Elena
city: Rozzano
country: Italy
facility: Istituto Clinico Humanitas I.R.C.C.S
city: Busan
country: Korea, Republic of
facility: Pusan National University Hospital
city: Cheongju-si
country: Korea, Republic of
facility: Chungbuk National University Hospital
city: Incheon
country: Korea, Republic of
facility: Gacheon University Gil Medical Center
city: Seoul
country: Korea, Republic of
facility: Korea University Guro Hospital
city: Cluj-Napoca
country: Romania
facility: Inst Oncologic "Prof Dr I Chiricuta" Cluj Napoca
city: Craiova
country: Romania
facility: Centrul de Oncologie Sf Nectarie
city: Otopeni
country: Romania
facility: Centrul de Radioterapie Amethyst
city: Ploieşti
country: Romania
facility: Ploiesti Municipal Hospital
city: Barcelona
country: Spain
facility: Val de Hebron Institute of Oncology (Vhio), University Hospital
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañón
city: Madrid
country: Spain
facility: Clinica Universitaria de Navarra (Madrid)
city: Madrid
country: Spain
facility: Hospital Univ. Hm Sanchinarro Start Ciocc Early Phase
city: Málaga
country: Spain
facility: Hospital Universitario Virgen de La Victoria
city: Pamplona
country: Spain
facility: Clinica Universitaria de Navarra (Pamplona)
city: Sevilla
country: Spain
facility: Hospital Virgen Del Rocío
city: Valencia
country: Spain
facility: Hospital Universitario Y Politecnico La Fe
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Tri-Service General Hospital
city: London
country: United Kingdom
facility: The Royal Marsden in Sutton
city: London
country: United Kingdom
facility: The Royal Marsden in Chelsea
city: London
country: United Kingdom
facility: Imperial College London
city: Manchester
country: United Kingdom
facility: The Christie Nhs Foundation Foundation Trust
Study officials:
References: