A Phase 2 Peri-Operative Trial of Fianlimab and Cemiplimab in Combination With Chemotherapy Versus Cemiplimab in Combination With Chemotherapy in Patients With Resectable Early Stage (Stage II to IIIB [N2]) NSCLC
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 195
- 试验地点
- 209
- 主要终点
- Pathological complete response (pCR) as evaluated by blinded independent pathological review (BIPR) in post-treatment resected tumor samples
研究概览
简要总结
This study is researching an experimental drug called fianlimab (also called REGN3767) with two other medications called cemiplimab and platinum-doublet chemotherapy, individually called a "study drug" or collectively called "study drugs", when combined in this study. The study is being conducted in patients who have resectable stage II to IIIB (N2) non-small cell lung cancer (NSCLC) that can be treated with surgery.
The aim of the study is to see how effective the combination of fianlimab, cemiplimab, and chemotherapy is in comparison with cemiplimab and chemotherapy as peri-operative therapy in participants with NSCLC.
The study is looking at several other research questions, including:
- What side effects may happen from taking the study drugs
- How much of each study drug is in the blood at different times
- Whether the body makes antibodies against the study drugs (which could make the drugs less effective or could lead to side effects)
- How administering the study drugs might affect quality of life
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Patients with newly diagnosed, histologically confirmed, fully resectable stage II to IIIB (N2) NSCLC as per American Joint Committee on Cancer (AJCC) version 8
- •For patients with evidence of mediastinal adenopathy on imaging, mediastinal lymph node sampling is required as defined in the protocol
- •All patients must have disease status showing no evidence of distant metastases documented by a complete physical examination and imaging studies performed within 4 weeks prior to randomization as defined in the protocol
- •A patient must have an evaluable Programmed cell death ligand-1 (PD-L1) immunohistochemistry (IHC) result as defined in the protocol
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- •Adequate bone marrow, hepatic and kidney function as defined in the protocol
排除标准
- •Any evidence of locally advanced unresectable or metastatic disease as defined in the protocol
- •Patients with tumors with known Epidermal growth factor receptor (EGFR) gene mutations, anaplastic lymphoma kinase (ALK) gene translocations as defined in the protocol
- •Uncontrolled infection with human immunodeficiency virus (HIV), hepatitis B (HBV) or hepatitis C virus (HCV) infection as defined in the protocol
- •Treatment with anti-cancer therapy including immunotherapy, chemotherapy, radiotherapy, or biological therapy in the 3 years prior to randomization. Adjuvant hormonotherapy used for breast cancer or other hormone-sensitive cancers in long term remission is allowed.
- •Patients with a history of myocarditis
- •Note: Other protocol-defined Inclusion/ Exclusion Criteria apply
研究组 & 干预措施
Arm C
Randomized 1:1:1
Neoadjuvant period:
fianlimab low dose + cemiplimab + platinum doublet chemotherapy
Adjuvant Period:
fianlimab low dose + cemiplimab
干预措施: Fianlimab (Drug)
Arm A
Randomized 1:1:1
Neoadjuvant period:
placebo + cemiplimab + platinum doublet chemotherapy
Adjuvant period:
placebo + cemiplimab
干预措施: Paclitaxel (Drug)
Arm A
Randomized 1:1:1
Neoadjuvant period:
placebo + cemiplimab + platinum doublet chemotherapy
Adjuvant period:
placebo + cemiplimab
干预措施: Pemetrexed (Drug)
Arm B
Randomized 1:1:1
Neoadjuvant period:
fianlimab high dose + cemiplimab + platinum doublet chemotherapy
Adjuvant period:
fianlimab high dose + cemiplimab
干预措施: Fianlimab (Drug)
Arm A
Randomized 1:1:1
Neoadjuvant period:
placebo + cemiplimab + platinum doublet chemotherapy
Adjuvant period:
placebo + cemiplimab
干预措施: Placebo (Drug)
Arm B
Randomized 1:1:1
Neoadjuvant period:
fianlimab high dose + cemiplimab + platinum doublet chemotherapy
Adjuvant period:
fianlimab high dose + cemiplimab
干预措施: Carboplatin (Drug)
Arm A
Randomized 1:1:1
Neoadjuvant period:
placebo + cemiplimab + platinum doublet chemotherapy
Adjuvant period:
placebo + cemiplimab
干预措施: Cemiplimab (Drug)
Arm A
Randomized 1:1:1
Neoadjuvant period:
placebo + cemiplimab + platinum doublet chemotherapy
Adjuvant period:
placebo + cemiplimab
干预措施: Carboplatin (Drug)
Arm B
Randomized 1:1:1
Neoadjuvant period:
fianlimab high dose + cemiplimab + platinum doublet chemotherapy
Adjuvant period:
fianlimab high dose + cemiplimab
干预措施: Pemetrexed (Drug)
Arm A
Randomized 1:1:1
Neoadjuvant period:
placebo + cemiplimab + platinum doublet chemotherapy
Adjuvant period:
placebo + cemiplimab
干预措施: Cisplatin (Drug)
Arm B
Randomized 1:1:1
Neoadjuvant period:
fianlimab high dose + cemiplimab + platinum doublet chemotherapy
Adjuvant period:
fianlimab high dose + cemiplimab
干预措施: Cemiplimab (Drug)
Arm B
Randomized 1:1:1
Neoadjuvant period:
fianlimab high dose + cemiplimab + platinum doublet chemotherapy
Adjuvant period:
fianlimab high dose + cemiplimab
干预措施: Paclitaxel (Drug)
Arm C
Randomized 1:1:1
Neoadjuvant period:
fianlimab low dose + cemiplimab + platinum doublet chemotherapy
Adjuvant Period:
fianlimab low dose + cemiplimab
干预措施: Cemiplimab (Drug)
Arm B
Randomized 1:1:1
Neoadjuvant period:
fianlimab high dose + cemiplimab + platinum doublet chemotherapy
Adjuvant period:
fianlimab high dose + cemiplimab
干预措施: Cisplatin (Drug)
Arm C
Randomized 1:1:1
Neoadjuvant period:
fianlimab low dose + cemiplimab + platinum doublet chemotherapy
Adjuvant Period:
fianlimab low dose + cemiplimab
干预措施: Pemetrexed (Drug)
Arm C
Randomized 1:1:1
Neoadjuvant period:
fianlimab low dose + cemiplimab + platinum doublet chemotherapy
Adjuvant Period:
fianlimab low dose + cemiplimab
干预措施: Paclitaxel (Drug)
Arm C
Randomized 1:1:1
Neoadjuvant period:
fianlimab low dose + cemiplimab + platinum doublet chemotherapy
Adjuvant Period:
fianlimab low dose + cemiplimab
干预措施: Carboplatin (Drug)
Arm C
Randomized 1:1:1
Neoadjuvant period:
fianlimab low dose + cemiplimab + platinum doublet chemotherapy
Adjuvant Period:
fianlimab low dose + cemiplimab
干预措施: Cisplatin (Drug)
结局指标
主要结局
Pathological complete response (pCR) as evaluated by blinded independent pathological review (BIPR) in post-treatment resected tumor samples
时间窗: Up to 24 months
次要结局
- Percentage of patients with definitive surgery(Up to 24 months)
- Percentage of patients with cancelled surgery(Up to 24 months)
- Median length of hospital stay(Up to 24 months)
- Anti-drug antibodies (ADA) to fianlimab in serum over time(Up to 30 months)
- Major pathological response (MPR) by BIPR in post-treatment resected tumor samples(Up to 24 months)
- Occurrence of interruption and discontinuation of study drug(s) due to TEAE(Up to 5 years)
- Concentrations of fianlimab in serum(Up to 30 months)
- Event-Free Survival (EFS)(Up to 3 years)
- Tumor response to neoadjuvant therapy per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) criteria by investigator assessment(Up to 24 months)
- Occurrence of Treatment-emergent adverse event (TEAEs)(Up to 5 years)
- Occurrence of Adverse events of special interest (AESIs)(Up to 5 years)
- Occurrence of immune-mediated adverse events (imAEs)(Up to 5 years)
- Concentrations of cemiplimab in serum(Up to 30 months)
- MPR by local pathology review in post-treatment resected tumor samples(Up to 24 months)
- Occurrence of Adverse events (AEs)(Up to 5 years)
- Occurrence of Serious adverse events (SAEs)(Up to 5 years)
- Occurrence of laboratory abnormalities(Up to 5 years)
- Occurrence of death due to TEAE(Up to 5 years)
- ADA to cemiplimab in serum over time(Up to 30 months)
- Overall change in patient-reported role functioning per EORTC QLQ-C30(Up to 5 years)
- Percentage of patients with delayed surgery(Up to 24 months)
- Completeness of resection (R0, R1, R2, Rx)(Up to 24 months)
- Surgical approach (thoracotomy, minimally invasive, minimally invasive to thoracotomy)(Up to 24 months)
- Overall change in patient-reported physical functioning per EORTC QLQ-C30(Up to 5 years)
- Overall change in patient-reported chest pain per European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer 13 (EORTC QLQ-LC13)(Up to 5 years)
- Change in patient-reported general health status per EuroQoL 5-Dimensional 5-Level Scale (EQ-5D-5L) index(Up to 5 years)
- Length in delay of surgery(Up to 24 months)
- Type of surgery (lobectomy, sleeve lobectomy, bilobectomy, pneumonectomy, other)(Up to 24 months)
- Incidence of post operative AE associated with surgery(Up to 90 days post-surgery)
- Overall change in patient-reported cough per EORTC QLQ-LC13(Up to 5 years)
- Overall change in patient-reported composite of chest pain, dyspnea, and cough per EORTC QLQ-LC13(Up to 5 years)
- Time until definitive deterioration in patient-reported global health status/QoL per EORTC QLQ-C30(Up to 5 years)
- Incidence of peri operative AE associated with surgery(Up to 90 days post-surgery)
- Incidence of peri operative SAE associated with surgery(Up to 90 days post-surgery)
- Incidence of post operative SAE associated with surgery(Up to 90 days post-surgery)
- Overall change in patient-reported global health status/QoL per European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30)(Up to 5 years)
- Overall change in patient-reported dyspnea per EORTC QLQ-LC13(Up to 5 years)
- Change in patient-reported general health status per Visual analogue scale (VAS) scores(Up to 5 years)
- Time until definitive deterioration in patient-reported physical functioning per EORTC QLQ-C30(Up to 5 years)
- Time until definitive deterioration in patient-reported role functioning per EORTC QLQ-C30(Up to 5 years)
- Time until definitive deterioration in patient-reported chest pain per EORTC QLQ-LC13(Up to 5 years)
- Time until definitive deterioration in patient-reported cough per EORTC QLQ-LC13(Up to 5 years)
- Time until definitive deterioration in patient-reported dyspnea per EORTC QLQ-LC13(Up to 5 years)
- Time until definitive deterioration in patient-reported composite of chest pain, dyspnea and cough per EORTC QLQ-LC13(Up to 5 years)