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

Activo, no reclutaFase 2ClinicalTrials.gov

ID: NCT06162572Tipo: INTERVENTIONALInicio: 7 de ago de 2024Fin estimado: 1 de jul de 2027

Traducción no disponible, mostrando original

Resumen

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.

Elegibilidad

Edad mínima: 18 YearsSexo: ALL

Criterios de inclusión

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

Criterios de exclusión

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