A Randomized, Double-blind, Placebo-controlled, Phase III Study Evaluating the Efficacy and Safety of Pembrolizumab Plus Platinum-based Doublet Chemotherapy With or Without Canakinumab as First Line Therapy for Locally Advanced or Metastatic Non-squamous and Squamous Non-small Cell Lung Cancer Subjects (CANOPY-1)
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 673
- 试验地点
- 157
- 主要终点
- Part 1 (Safety Run-in): Number of Participants With Dose-limiting Toxicities (DLTs)
研究概览
简要总结
This was a Phase III study of pembrolizumab plus platinum-based doublet chemotherapy with or without canakinumab in previously untreated locally advanced or metastatic non-squamous and squamous NSCLC participants.
详细描述
The study primarily assessed the safety and tolerability (safety run-in Part A) of pembrolizumab plus platinum-based doublet chemotherapy with canakinumab, and then, the efficacy (double-blind, randomized, placebo-controlled Part B) of pembrolizumab plus platinum-based doublet chemotherapy with or without canakinumab.
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 100 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed locally advanced stage IIIB or stage IV NSCLC for treatment in the first-line setting
- •Known PD-L1 status determined by a Novartis designated central laboratory. A newly obtained tissue biopsy or an archival biopsy (block or slides) is required for PD-L1 determination (PD-L1 IHC 22C3 pharmDx assay), prior to study randomization. Note: For the safety run-in part, known PD-L1 status is not required.
- •Eastern Cooperative oncology group (ECOG) performance status of 0 or
- •At least 1 measurable lesion by RECIST 1.1
排除标准
- •Previous immunotherapy (e.g. anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways).
- •Prior treatment with canakinumab or drugs of a similar mechanism of action (IL-1β inhibitor).
- •Subjects with epidermal growth factor receptor (EGFR) sensitizing mutations (identified in exons 19, 20, or 21), and/or ALK rearrangement by locally approved laboratory testing.
- •Previously untreated or symptomatic central nervous system (CNS) metastases or lepto-meningeal disease.
- •Subject with suspected or proven immune-compromised state or infections.
- •Subject has prior to starting study drug: received live vaccination ≤3 months, had major surgery ≤4 weeks prior to starting study drug, has thoracic radiotherapy: lung fields ≤ 4 weeks, other anatomic sites ≤ 2 weeks, palliative radiotherapy for bone lesions ≤ 2 weeks.
研究组 & 干预措施
Part 1: Cohort A
Safety run-in, canakinumab in combination with pembrolizumab, carboplatin, and pemetrexed.
干预措施: canakinumab (Drug)
Part 1: Cohort A
Safety run-in, canakinumab in combination with pembrolizumab, carboplatin, and pemetrexed.
干预措施: pembrolizumab (Drug)
Part 2: Placebo+pembro+CTx
Double-blind, randomized, placebo-controlled, canakinumab-matching placebo in combination with pembrolizumab and platinum-based doublet chemotherapy.
干预措施: canakinumab-matching placebo (Drug)
Part 2: Placebo+pembro+CTx
Double-blind, randomized, placebo-controlled, canakinumab-matching placebo in combination with pembrolizumab and platinum-based doublet chemotherapy.
干预措施: nab-paclitaxel (Drug)
Part 2: Placebo+pembro+CTx
Double-blind, randomized, placebo-controlled, canakinumab-matching placebo in combination with pembrolizumab and platinum-based doublet chemotherapy.
干预措施: pembrolizumab (Drug)
Part 2: Placebo+pembro+CTx
Double-blind, randomized, placebo-controlled, canakinumab-matching placebo in combination with pembrolizumab and platinum-based doublet chemotherapy.
干预措施: carboplatin (Drug)
Part 2: Placebo+pembro+CTx
Double-blind, randomized, placebo-controlled, canakinumab-matching placebo in combination with pembrolizumab and platinum-based doublet chemotherapy.
干预措施: cisplatin (Drug)
Part 2: Placebo+pembro+CTx
Double-blind, randomized, placebo-controlled, canakinumab-matching placebo in combination with pembrolizumab and platinum-based doublet chemotherapy.
干预措施: paclitaxel (Drug)
Part 2: Canakinumab+pembro+CTx
Double-blind, randomized, placebo-controlled, canakinumab in combination with pembrolizumab and platinum-based doublet chemotherapy.
干预措施: nab-paclitaxel (Drug)
Part 1: Cohort B
Safety run-in, canakinumab in combination with pembrolizumab, cisplatin, and pemetrexed.
干预措施: pembrolizumab (Drug)
Part 1: Cohort B
Safety run-in, canakinumab in combination with pembrolizumab, cisplatin, and pemetrexed.
干预措施: canakinumab (Drug)
Part 1: Cohort B
Safety run-in, canakinumab in combination with pembrolizumab, cisplatin, and pemetrexed.
干预措施: cisplatin (Drug)
Part 1: Cohort A
Safety run-in, canakinumab in combination with pembrolizumab, carboplatin, and pemetrexed.
干预措施: carboplatin (Drug)
Part 1: Cohort A
Safety run-in, canakinumab in combination with pembrolizumab, carboplatin, and pemetrexed.
干预措施: pemetrexed (Drug)
Part 2: Canakinumab+pembro+CTx
Double-blind, randomized, placebo-controlled, canakinumab in combination with pembrolizumab and platinum-based doublet chemotherapy.
干预措施: cisplatin (Drug)
Part 1: Cohort C
Safety run-in, canakinumab in combination with pembrolizumab, carboplatin, and paclitaxel.
干预措施: canakinumab (Drug)
Part 1: Cohort B
Safety run-in, canakinumab in combination with pembrolizumab, cisplatin, and pemetrexed.
干预措施: pemetrexed (Drug)
Part 1: Cohort C
Safety run-in, canakinumab in combination with pembrolizumab, carboplatin, and paclitaxel.
干预措施: pembrolizumab (Drug)
Part 1: Cohort C
Safety run-in, canakinumab in combination with pembrolizumab, carboplatin, and paclitaxel.
干预措施: carboplatin (Drug)
Part 1: Cohort C
Safety run-in, canakinumab in combination with pembrolizumab, carboplatin, and paclitaxel.
干预措施: paclitaxel (Drug)
Part 2: Canakinumab+pembro+CTx
Double-blind, randomized, placebo-controlled, canakinumab in combination with pembrolizumab and platinum-based doublet chemotherapy.
干预措施: pembrolizumab (Drug)
Part 2: Canakinumab+pembro+CTx
Double-blind, randomized, placebo-controlled, canakinumab in combination with pembrolizumab and platinum-based doublet chemotherapy.
干预措施: canakinumab (Drug)
Part 2: Canakinumab+pembro+CTx
Double-blind, randomized, placebo-controlled, canakinumab in combination with pembrolizumab and platinum-based doublet chemotherapy.
干预措施: carboplatin (Drug)
Part 2: Canakinumab+pembro+CTx
Double-blind, randomized, placebo-controlled, canakinumab in combination with pembrolizumab and platinum-based doublet chemotherapy.
干预措施: paclitaxel (Drug)
Part 2: Canakinumab+pembro+CTx
Double-blind, randomized, placebo-controlled, canakinumab in combination with pembrolizumab and platinum-based doublet chemotherapy.
干预措施: pemetrexed (Drug)
Part 2: Placebo+pembro+CTx
Double-blind, randomized, placebo-controlled, canakinumab-matching placebo in combination with pembrolizumab and platinum-based doublet chemotherapy.
干预措施: pemetrexed (Drug)
结局指标
主要结局
Part 1 (Safety Run-in): Number of Participants With Dose-limiting Toxicities (DLTs)
时间窗: During the first 42 days of dosing
A DLT was defined as an adverse event or abnormal laboratory value assessed as unrelated to disease progression, inter-current illness, or concomitant medications that met certain criteria as defined in the protocol.
Part 2 (Double-blind, Randomized, Placebo-controlled): Progression-free Survival (PFS) Per Investigator Assessment Using RECIST v1.1
时间窗: 18 months
Progression free survival was defined as the time from randomization to the date of the first documented radiological progression using RECIST 1.1 (Response evaluation criteria in solid tumor) or death due to any cause.
Part 2 (Double-blind, Randomized, Placebo-controlled): Overall Survival (OS) Per Investigator Assessment Using RECIST v1.1
时间窗: Up to approximately 32 months
Overall survival is defined as the time from date of randomization to date of death due to any cause.
次要结局
- Part 1 (Safety Run-in): Serum Pembrolizumab Concentration(Predose (0 h) on Day 1 of Cycles 1-6, 8, 12, 16, Postdose on day 2, 8, 15 of Cycle 1, at end of treatment & then at 26 days after last dose (Cycle length =21 days))
- Part 2 (Double-blind, Randomized, Placebo-controlled): Serum Pembrolizumab Concentration(Predose (0 h) on Day 1 of Cycles 1-6, 8, 12, 16, Postdose on day 2, 8, 15 of Cycle 1, at end of treatment & then at 26 days after last dose (Cycle length =21 days))
- Part 1 (Safety Run-in): Plasma Pemetrexed Concentration(Predose (0 h) and end of infusion on Cycle 1 and 2; 1, 4, 8 h post infusion on Cycle 1; 1, 2, 4, 8h post infusion on Cycle 2 (Cycle length =21 days))
- Part 2 (Double-blind, Randomized, Placebo-controlled): Plasma Pemetrexed Concentration(Predose (0 h) and end of infusion on Cycle 1 and 2; 1, 4, 8 h post infusion on Cycle 1; 1, 2, 4, 8h post infusion on Cycle 2 (Cycle length =21 days))
- Part 1 (Safety Run-in): Plasma Cisplatin Concentration(Predose (0 h) and end of infusion on Cycle 1 and 2; 2, 4, 8 h post infusion on Cycle 1; 1.5, 2, 4, 8 h post infusion on Cycle 2 (Cycle length =21 days))
- Part 2 (Double-blind, Randomized, Placebo-controlled): Plasma Cisplatin Concentration(Predose (0 h) and end of infusion on Cycle 1 and 2; 2, 4, 8 h post infusion on Cycle 1; 1.5, 2, 4, 8 h post infusion on Cycle 2 (Cycle length = 21 days))
- Part 1 (Safety Run-in): Overall Response Rate (ORR) Per Investigator Assessment Using RECIST v1.1(Up to approximately 14 months)
- Part 1 (Safety run-in): Duration of Response (DOR) Per Investigator Assessment Using RECIST v1.1(Up to approximately 25 months)
- Part 2 (Double-blind, Randomized, Placebo-controlled): Duration of Response (DOR) Per Investigator Assessment Using RECIST v1.1(Up to approximately 26 months)
- Part 2 (Double-blind, Randomized, Placebo-controlled): Time to Response (TTR) Per Investigator Assessment Using RECIST v1.1(Up to approximately 26 months)
- Part 1 (Safety Run-in): Antidrug Antibodies (ADA) of Canakinumab(Predose (0 hours (h)) on Day 1 of Cycles 1, 4, 8, 12, 16 (Cycle length =21 days), at end of treatment & then at 26, 78 and 130 days after last dose)
- Part 2 (Double-blind, Randomized, Placebo-controlled): Number of Participants With Antidrug Antibodies (ADA) of Canakinumab(Up to approximately 26 months)
- Part 1 (Safety run-in): Antidrug Antibodies (ADAs) of Pembrolizumab(Predose (0 h) on Day 1 of Cycles 1, 2, 4, 8, 12, 16 (Cycle length =21 days), at end of treatment & then at 26 days after last dose)
- Part 2 (Double-blind, Randomized, Placebo-controlled): Antidrug Antibodies (ADA) of Pembrolizumab(Up to approximately 26 months)
- Part 1 (Safety Run-in): Serum Canakinumab Concentration(Predose (0 h) on Day 1 of Cycles 1-6, 8, 12, 16, Postdose on day 2, 8, 15 of Cycle 1, Post dose on Cycle 5 day 8, at end of treatment & then at 26, 78 and 130 days after last dose (Cycle length =21 days))
- Part 2 (Double-blind, Randomized, Placebo-controlled): Serum Canakinumab Concentration(Predose (0 h) on Day 1 of Cycles 1-6, 8, 12, 16, Postdose on day 2, 8, 15 of Cycle 1, Post dose on Cycle 5 day 8, at end of treatment & then at 26, 78 and 130 days after last dose (Cycle length =21 days))
- Part 2 (Double-blind, Randomized, Placebo-controlled): Time to Definitive Deterioration in Global Health Status/Quality of Life, Shortness of Breath and Pain Per EORTC QLQ-C30 Questionnaire(Up to approximately 25 months)
- Part 2 (Double-blind, Randomized, Placebo-controlled): Change From Baseline in Score as Per the EuroQol 5 Dimension 5 Level (EQ-5D-5L) Questionnaire(Assessed every 3 weeks from Week 3 through Week 108, at follow-up visits 1, 2, 3, 4, and 5 (follow-up visits occurred every 26 days from week 108), and at 7 and 28 days post-disease progression, all up to a maximum of 3.5 years)
- Part 2 (Double-blind, Randomized, Placebo-controlled): Change From Baseline in Score as Per the EuroQol 5 Dimension 5 Level (EQ-5D-5L) Questionnaire - Visual Analog Scale (VAS)(Assessed every 3 weeks from Week 3 through Week 108, at follow-up visits 1, 2, 3, 4, and 5 (follow-up visits occurred every 26 days from week 108), and at 7 and 28 days post-disease progression, all up to a maximum of 3.5 years)
- Part 1 (Safety Run-in): Serum Pembrolizumab Concentration(Predose (0 h) on Day 1 of Cycles 1-6, 8, 12, 16, Postdose on day 2, 8, 15 of Cycle 1, at end of treatment & then at 26 days after last dose (Cycle length =21 days))
- Part 1 (Safety Run-in): Overall Response Rate (ORR) Per Investigator Assessment Using RECIST v1.1(Up to approximately 14 months)
- Part 2 (Double-blind, Randomized, Placebo-controlled): Overall Response Rate (ORR) Per Investigator Assessment Using RECIST v1.1(Up to approximately 26 months)
- Part 1 (Safety run-in): Disease Control Rate (DCR) Per Investigator Assessment Using RECIST v1.1(Up to approximately 14 months)
- Part 2 (Double-blind, Randomized, Placebo-controlled): Disease Control Rate (DCR) Per Investigator Assessment Using RECIST v1.1(Up to approximately 26 months)
- Part 1 (Safety run-in): Duration of Response (DOR) Per Investigator Assessment Using RECIST v1.1(Up to approximately 25 months)
- Part 2 (Double-blind, Randomized, Placebo-controlled): Duration of Response (DOR) Per Investigator Assessment Using RECIST v1.1(Up to approximately 26 months)
- Part 2 (Double-blind, Randomized, Placebo-controlled): Time to Response (TTR) Per Investigator Assessment Using RECIST v1.1(Up to approximately 26 months)
- Part 1 (Safety Run-in): Antidrug Antibodies (ADA) of Canakinumab(Predose (0 hours (h)) on Day 1 of Cycles 1, 4, 8, 12, 16 (Cycle length =21 days), at end of treatment & then at 26, 78 and 130 days after last dose)
- Part 2 (Double-blind, Randomized, Placebo-controlled): Number of Participants With Antidrug Antibodies (ADA) of Canakinumab(Up to approximately 26 months)
- Part 1 (Safety run-in): Antidrug Antibodies (ADAs) of Pembrolizumab(Predose (0 h) on Day 1 of Cycles 1, 2, 4, 8, 12, 16 (Cycle length =21 days), at end of treatment & then at 26 days after last dose)
- Part 2 (Double-blind, Randomized, Placebo-controlled): Antidrug Antibodies (ADA) of Pembrolizumab(Up to approximately 26 months)
- Part 1 (Safety Run-in): Serum Canakinumab Concentration(Predose (0 h) on Day 1 of Cycles 1-6, 8, 12, 16, Postdose on day 2, 8, 15 of Cycle 1, Post dose on Cycle 5 day 8, at end of treatment & then at 26, 78 and 130 days after last dose (Cycle length =21 days))
- Part 2 (Double-blind, Randomized, Placebo-controlled): Serum Canakinumab Concentration(Predose (0 h) on Day 1 of Cycles 1-6, 8, 12, 16, Postdose on day 2, 8, 15 of Cycle 1, Post dose on Cycle 5 day 8, at end of treatment & then at 26, 78 and 130 days after last dose (Cycle length =21 days))
- Part 2 (Double-blind, Randomized, Placebo-controlled): Serum Pembrolizumab Concentration(Predose (0 h) on Day 1 of Cycles 1-6, 8, 12, 16, Postdose on day 2, 8, 15 of Cycle 1, at end of treatment & then at 26 days after last dose (Cycle length =21 days))
- Part 1 (Safety Run-in): Plasma Pemetrexed Concentration(Predose (0 h) and end of infusion on Cycle 1 and 2; 1, 4, 8 h post infusion on Cycle 1; 1, 2, 4, 8h post infusion on Cycle 2 (Cycle length =21 days))
- Part 2 (Double-blind, Randomized, Placebo-controlled): Plasma Pemetrexed Concentration(Predose (0 h) and end of infusion on Cycle 1 and 2; 1, 4, 8 h post infusion on Cycle 1; 1, 2, 4, 8h post infusion on Cycle 2 (Cycle length =21 days))
- Part 1 (Safety Run-in): Plasma Cisplatin Concentration(Predose (0 h) and end of infusion on Cycle 1 and 2; 2, 4, 8 h post infusion on Cycle 1; 1.5, 2, 4, 8 h post infusion on Cycle 2 (Cycle length =21 days))
- Part 2 (Double-blind, Randomized, Placebo-controlled): Plasma Cisplatin Concentration(Predose (0 h) and end of infusion on Cycle 1 and 2; 2, 4, 8 h post infusion on Cycle 1; 1.5, 2, 4, 8 h post infusion on Cycle 2 (Cycle length = 21 days))
- Part 1 (Safety Run-in): Plasma Carboplatin Concentration(Predose (0 h), end of infusion, 1, 2, 4, 8 h post infusion on Cycles 1 and 2 (Cycle length =21 days))
- Part 2 (Double-blind, Randomized, Placebo-controlled): Plasma Carboplatin Concentration(Predose (0 h), end of infusion, 1, 2, 4, 8 h post infusion on Cycles 1 and 2 (Cycle length =21 days))
- Part 1 (Safety Run-in): Plasma Paclitaxel Concentration(Predose (0 h) and end of infusion on Cycle 1 and 2; 4, 8, 12 h post infusion on Cycle 1; 4, 6, 8, 12 h post infusion on Cycle 2 (Cycle length =21 days))
- Part 2 (Double-blind, Randomized, Placebo-controlled): Plasma Paclitaxel Concentration(Predose (0 h) and end of infusion on Cycle 1 and 2; 4, 8, 12 h post infusion on Cycle 1; 4, 6, 8, 12 h post infusion on Cycle 2 (Cycle length =21 days))
- Part 2 (Double-blind, Randomized, Placebo-controlled): Plasma Nab-paclitaxel Concentration(Predose (0 h) and end of infusion on Cy 1 and 2, 4, 8, 12 h post infusion on Cy 1, 4, 6, 8, 12 h post infusion on Cy 2 (Cy length =21 days))
- Part 2 (Double-blind, Randomized, Placebo-controlled): Time to Definitive 10-point Deterioration (TTDD) Symptom Scores of Pain, Cough and Dyspnea Per EORTC QLQ-LC13 Questionnaire(Up to approximately 25 months)
- Part 2 (Double-blind, Randomized, Placebo-controlled): Time to Definitive Deterioration in Global Health Status/Quality of Life, Shortness of Breath and Pain Per EORTC QLQ-C30 Questionnaire(Up to approximately 25 months)
- Part 2 (Double-blind, Randomized, Placebo-controlled): Change From Baseline in Score as Per the EuroQol 5 Dimension 5 Level (EQ-5D-5L) Questionnaire(Assessed every 3 weeks from Week 3 through Week 108, at follow-up visits 1, 2, 3, 4, and 5 (follow-up visits occurred every 26 days from week 108), and at 7 and 28 days post-disease progression, all up to a maximum of 3.5 years)
- Part 2 (Double-blind, Randomized, Placebo-controlled): Change From Baseline in Score as Per the EuroQol 5 Dimension 5 Level (EQ-5D-5L) Questionnaire - Visual Analog Scale (VAS)(Assessed every 3 weeks from Week 3 through Week 108, at follow-up visits 1, 2, 3, 4, and 5 (follow-up visits occurred every 26 days from week 108), and at 7 and 28 days post-disease progression, all up to a maximum of 3.5 years)