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

Plain English Summary

Phase 1b/2 Platform Study of Select Immunotherapy Combinations in Participants With Advanced Non-small Cell Lung Cancer (NSCLC) is a Phase 2 clinical trial sponsored by Servier Bio-Innovation LLC studying Non-small Cell Lung Cancer (NSCLC). This study tests new combinations of immunotherapy drugs to treat advanced non-small cell lung cancer (NSCLC) in adults who have not received prior treatment. It is for patients with advanced or metastatic NSCLC that has high levels of a protein called PD-L1 on cancer cells. Participants will receive one of several investigational drug combinations via IV infusion. Alternative treatments for this condition include chemotherapy, radiation, and other immunotherapies. The trial aims to enroll 101 participants.

Official 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.

Who Can Participate

Here is what you need to know about eligibility for this trial. Adults aged 18 and older with advanced or metastatic NSCLC. Patients must have high PD-L1 expression (50% or more) and good general health (ECOG 0 or 1). Cannot have received prior immunotherapy or have specific genetic mutations in their cancer for which targeted treatments exist. Cannot have active brain metastases or uncontrolled autoimmune conditions. This trial is studying Non-small Cell Lung Cancer (NSCLC), so participants generally need a confirmed diagnosis.

What They're Measuring

The study will measure how safe the new drug combinations are and how well they shrink tumors or control cancer growth, aiming to find effective and tolerable treatments for patients. The specific primary outcome measures are: 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)); Incidence and severity of adverse events (AEs) (From the signed informed consent form (ICF) to 30 days after the last dose); Incidence and severity of serious adverse events (SAEs) (From the signed ICF to 120 days after the last dose); Adverse Events (AEs) Leading to Dose Interruption, Modification, or Delays (From signed ICF through treatment discontinuation (up to 108 weeks of treatment)); Adverse Events (AEs) Leading to Permanent Treatment Discontinuation (From signed ICF through treatment discontinuation (up to 108 weeks of treatment)). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 2, which tests whether the treatment actually works against the target condition. Phase 2 trials involve 100-300 patients and continue to monitor safety while evaluating effectiveness. This phase often tests different dosages to find the optimal amount. About 33% of Phase 2 drugs advance to Phase 3. If successful, the treatment will move to large-scale Phase 3 trials needed for FDA approval.

Why This Trial Matters

This trial explores new ways to combine immunotherapies to potentially improve outcomes for patients with advanced lung cancer who have specific biomarkers, addressing a need for more effective first- Phase 2 success would typically lead to larger Phase 3 trials needed for regulatory approval. This research targets Non-small Cell Lung Cancer (NSCLC), where improved treatment options are needed.

Investor Insight

This trial investigates novel immunotherapy combinations for a significant unmet need in first-line advanced NSCLC, potentially offering a competitive advantage if successful. Phase 2 trials have approximately a 15-20% chance of eventually gaining FDA approval.

Is This Trial Right for Me?

Ask your doctor if your cancer has high PD-L1 expression and if you have any genetic mutations that might affect treatment options. Be prepared for regular IV infusions and potential side effects, which will be closely monitored. Understand that this is an open-label study, meaning both you and your doctor will know which treatment you are receiving. The trial is being conducted at 20 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: PARALLEL
• Masking: NONE
• Enrollment: 101 participants

Interventions

• DRUG: S095018 — Via IV infusion on Day 1 of each 21-day cycle
• DRUG: S095024 — Via IV infusion on Day 1 of each 21-day cycle
• DRUG: S095029 — Via IV infusion on Day 1 of each 21-day cycle
• DRUG: S095018 Recommended Dose Expansion (RDE) — Via IV infusion on Day 1 of each 21-day cycle
• DRUG: S095024 RDE — Via IV infusion on Day 1 of each 21-day cycle

Primary Outcomes

• 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))
• Incidence and severity of adverse events (AEs) (From the signed informed consent form (ICF) to 30 days after the last dose)
• Incidence and severity of serious adverse events (SAEs) (From the signed ICF to 120 days after the last dose)
• Adverse Events (AEs) Leading to Dose Interruption, Modification, or Delays (From signed ICF through treatment discontinuation (up to 108 weeks of treatment))
• Adverse Events (AEs) Leading to Permanent Treatment Discontinuation (From signed ICF through treatment discontinuation (up to 108 weeks of treatment))

Secondary Outcomes

• Objective Response (OR) (Until study termination (approximately 3 years))
• Best Overall Response (BOR) (Until study termination (approximately 3 years))
• Duration of Response (DoR) (Until study termination (approximately 3 years))
• Disease Control (DC) (Until study termination (approximately 3 years))
• 6-month Durable Response (6-month DR) (Until study termination (approximately 3 years))

Full 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)
* 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

Trial Locations

• Loma Linda University, Loma Linda, California, 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, Buenos Aires, Argentina
• Sanatorio Parque S.A., Santa Fe, Argentina
• Border Medical Oncology Research Unit, Albury, Australia
• Flinders Medical Centre, Bedford Park, Australia
• ...and 10 more locations

Frequently Asked Questions

Related Conditions

• Non-small Cell Lung Cancer (NSCLC)
• Lung Cancer
• Metastatic Cancer
• Oncology
• Immunotherapy
• Cancer
• Tumor
• Advanced Cancer
• Carcinoma
• Malignancy

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