Non-small Cell Lung Cancer (NSCLC)
Conditions
Keywords
Non-small Cell Lung Carcinoma
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.
Interventions
DRUGS095018
Via IV infusion on Day 1 of each 21-day cycle
DRUGS095024
Via IV infusion on Day 1 of each 21-day cycle
DRUGS095029
Via IV infusion on Day 1 of each 21-day cycle
DRUGS095018 Recommended Dose Expansion (RDE)
Via IV infusion on Day 1 of each 21-day cycle
DRUGS095024 RDE
Via IV infusion on Day 1 of each 21-day cycle
DRUGS095029 RDE
Via IV infusion on Day 1 of each 21-day cycle
DRUGCemiplimab
350 mg via IV infusion on Day 1 of each 21-day cycle
Sponsors
Servier Bio-Innovation LLC
Institut de Recherches Internationales Servier
Regeneron Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| Incidence and severity of serious adverse events (SAEs) | From the signed ICF to 120 days after the last dose | Part A |
| Adverse Events (AEs) Leading to Dose Interruption, Modification, or Delays | From signed ICF through treatment discontinuation (up to 108 weeks of treatment) | Part A |
| Adverse Events (AEs) Leading to Permanent Treatment Discontinuation | From signed ICF through treatment discontinuation (up to 108 weeks of treatment) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
| 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 S095024 | 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 |
| 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 S095024 | 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 |
| 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 Dose Interruption, Modification, or Delays | From signed ICF through treatment discontinuation (up to 108 weeks of treatment) | Part B |
| Adverse Events (AEs) Leading to Permanent Treatment Discontinuation | From signed ICF through treatment discontinuation (up to 108 weeks of treatment) | Part B |
Countries
Argentina, Australia, Austria, Belgium, Brazil, France, Hong Kong, Hungary, Italy, Romania, Spain, Taiwan, United Kingdom, United States
Outcome results
None listed