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
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 102
- 试验地点
- 118
- 主要终点
- Adverse Events (AEs) Leading to Dose Interruption, Modification, or Delays
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
S095029 (anti-NKG2A antibody) RDE in combination with cemiplimab
Part B: Randomized dose expansion
干预措施: S095029 RDE (Drug)
S095029 (anti-NKG2A antibody) RDE in combination with cemiplimab
Part B: Randomized dose expansion
干预措施: Cemiplimab (Drug)
Cemiplimab (control arm)
Part B: Randomized dose expansion
干预措施: Cemiplimab (Drug)
S095024 (anti-CD73 antibody) in combination with cemiplimab
Part A: Combination-therapy safety lead-in
干预措施: Cemiplimab (Drug)
S095029 (anti-NKG2A antibody) in combination with cemiplimab
Part A: Combination-therapy safety lead-in
干预措施: Cemiplimab (Drug)
S095018 (anti-TIM3 antibody) RDE in combination with cemiplimab
Part B: Randomized dose expansion
干预措施: Cemiplimab (Drug)
S095024 (anti-CD73 antibody) RDE in combination with cemiplimab
Part B: Randomized dose expansion
干预措施: Cemiplimab (Drug)
S095018 (anti-TIM3 antibody) RDE in combination with cemiplimab
Part B: Randomized dose expansion
干预措施: S095018 Recommended Dose Expansion (RDE) (Drug)
S095024 (anti-CD73 antibody) RDE in combination with cemiplimab
Part B: Randomized dose expansion
干预措施: S095024 RDE (Drug)
S095024 (anti-CD73 antibody) in combination with cemiplimab
Part A: Combination-therapy safety lead-in
干预措施: S095024 (Drug)
S095029 (anti-NKG2A antibody) in combination with cemiplimab
Part A: Combination-therapy safety lead-in
干预措施: S095029 (Drug)
S095018 (anti-TIM3 antibody) in combination with cemiplimab
Part A: Combination-therapy safety lead-in
干预措施: S095018 (Drug)
S095018 (anti-TIM3 antibody) in combination with cemiplimab
Part A: Combination-therapy safety lead-in
干预措施: Cemiplimab (Drug)
结局指标
主要结局
Adverse Events (AEs) Leading to Dose Interruption, Modification, or Delays
时间窗: From signed ICF through treatment discontinuation (up to 108 weeks of treatment)
Part A
Incidence and severity of serious adverse events (SAEs)
时间窗: From the signed ICF to 120 days after the last dose
Part A
Objective Response (OR)
时间窗: 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.
Incidence and severity of dose-limiting toxicities (DLTs) during the first 2 cycles of combination treatment
时间窗: Through the end of the Cycle 2 (each cycle is 21 days)
Part A
Incidence and severity of adverse events (AEs)
时间窗: From the signed informed consent form (ICF) to 30 days after the last dose
Part A
Adverse Events (AEs) Leading to Permanent Treatment Discontinuation
时间窗: From signed ICF through treatment discontinuation (up to 108 weeks of treatment)
Part A
次要结局
- Objective Response (OR)(Until study termination (approximately 3 years))
- Plasma or serum concentration of S095024(From first dose to 30 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))
- Disease Control (DC)(Until study termination (approximately 3 years))
- Duration of Response (DoR)(Until study termination (approximately 3 years))
- Incidence and titer of anti-drug antibodies (ADA) directed against S095018(From screening to 90 days after the last dose)
- Incidence and titer of anti-drug antibodies (ADA) directed against S095029(From screening to 90 days after the last dose)
- 6-month Durable Response (6-month DR)(Until study termination (approximately 3 years))
- Incidence and titer of anti-drug antibodies (ADA) directed against S095024(From screening to 90 days after the last dose)
- Incidence and severity of adverse events (AEs)(From signed ICF to 30 days after the last dose)
- Incidence and severity of serious adverse events (SAEs)(From signed ICF to 120 days after the last dose)
- Adverse Events (AEs) Leading to Permanent Treatment Discontinuation(From signed ICF through treatment discontinuation (up to 108 weeks of treatment))
- Best Overall Response (BOR)(Until study termination (approximately 3 years))
- Progression-Free Survival (PFS)(Until study termination (approximately 3 years))
- Plasma or serum concentration of S095018(From first dose to 30 days after the last dose)
- Plasma or serum concentration of S095029(From first dose to 30 days after the last dose)