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

Non-small Cell Lung Cancer (NSCLC) Clinical Trial

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06162572
• Other study ID #: SPLFIO-174
• Status: Not yet recruiting
• Phase: Phase 1/Phase 2
• Start date: June 7, 2024
• Est. completion date: July 2027

Study information

• Verified date: May 2024
• Source: Servier
• Contact: Institut de Recherches Internationales Servier (I.R.I.S.), Clini
• Phone: +33 1 55 72 60 00
• Email: scientificinformation[@]servier.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 176
• Est. completion date: July 2027
• Est. primary completion date: April 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

• 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

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-small Cell Lung Cancer (NSCLC)

Intervention

Drug:
• S095018
Via IV infusion on Day 1 of each 21-day cycle
• S095024
Via IV infusion on Day 1 of each 21-day cycle
• S095029
Via IV infusion on Day 1 of each 21-day cycle
• S095018 Recommended Dose Expansion (RDE)
Via IV infusion on Day 1 of each 21-day cycle
• S095024 RDE
Via IV infusion on Day 1 of each 21-day cycle
• S095029 RDE
Via IV infusion on Day 1 of each 21-day cycle
• Cemiplimab
350 mg via IV infusion on Day 1 of each 21-day cycle

Locations

Country	Name	City	State
Australia	Albury Wodonga Regional Cancer Centre; Border Medical Oncology Research Unit	Albury
Australia	Flinders Medical Centre	Bedford Park
Australia	Sunshine Hospital	St Albans
Hong Kong	Hong Kong United Onology Centre	Hong Kong
Hong Kong	Queen Mary Hospital	Hong Kong
Hong Kong	Sir Yue Kong Pao Centre for Cancer; Prince of Wales Hospital	Hong Kong
United States	Gabrail Cancer Center	Canton	Ohio
United States	Virginia Cancer Specialists, P.C.	Fairfax	Virginia

Sponsors (3)

Lead Sponsor	Collaborator
Servier Bio-Innovation LLC	Institut de Recherches Internationales Servier, Regeneron Pharmaceuticals

Countries where clinical trial is conducted

United States,  Australia,  Hong Kong, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	Incidence and severity of adverse events (AEs)	Part A	From the signed informed consent form (ICF) to 30 days after the last dose
Primary	Incidence and severity of serious adverse events (SAEs)	Part A	From the signed ICF to 120 days after the last dose
Primary	Adverse Events (AEs) Leading to Dose Interruption, Modification, or Delays	Part A	From signed ICF through treatment discontinuation (up to 108 weeks of treatment)
Primary	Adverse Events (AEs) Leading to Permanent Treatment Discontinuation	Part A	From signed ICF through treatment discontinuation (up to 108 weeks of treatment)
Primary	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	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	Plasma or serum concentration of S095018	Part A and B	From first dose to 30 days after the last dose
Secondary	Plasma or serum concentration of S095024	Part A and B	From first dose to 30 days after the last dose
Secondary	Plasma or serum concentration of S095029	Part A and B	From first dose to 30 days after the last dose
Secondary	Incidence and titer of anti-drug antibodies (ADA) directed against S095018	Part A and B	From screening to 90 days after the last dose
Secondary	Incidence and titer of anti-drug antibodies (ADA) directed against S095024	Part A and B	From screening to 90 days after the last dose
Secondary	Incidence and titer of anti-drug antibodies (ADA) directed against S095029	Part A and B	From screening to 90 days after the last dose
Secondary	Incidence and severity of adverse events (AEs)	Part B	From signed ICF to 30 days after the last dose
Secondary	Incidence and severity of serious adverse events (SAEs)	Part B	From signed ICF to 120 days after the last dose
Secondary	Adverse Events (AEs) Leading to Dose Interruption, Modification, or Delays	Part B	From signed ICF through treatment discontinuation (up to 108 weeks of treatment)
Secondary	Adverse Events (AEs) Leading to Permanent Treatment Discontinuation	Part B	From signed ICF through treatment discontinuation (up to 108 weeks of treatment)