A Randomized, Open-label, Phase II Study of Canakinumab or Pembrolizumab as Monotherapy or in Combination as Neoadjuvant Therapy in Subjects With Resectable Non-small Cell Lung Cancer (CANOPY-N)
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 88
- 试验地点
- 5
- 主要终点
- Major Pathological Response (MPR) Rate at the Time of Surgery in Subjects Randomized to Canakinumab Monotherapy and in Combination With Pembrolizumab Based on Central Review
研究概览
简要总结
The purpose of this study was to evaluate the major pathological response (MPR) rate of canakinumab given as a neoadjuvant treatment, either as single agent or in combination with pembrolizumab, in addition to evaluate the MPR of pembrolizumab as a single agent and the dynamic of the tumor microenvironment changes on treatment.
详细描述
This was a randomized, phase II, open-label study evaluating canakinumab, an anti-IL-1β monoclonal antibody, or pembrolizumab, a monoclonal antibody designed to block the PD-1 receptor, as monotherapy or in combination as neoadjuvant therapy. The study population included adult subjects with resectable non-small cell lung cancer (NSCLC) planned for surgery in approximately 4-6 weeks. Subjects were treated for a maximum duration of 6 weeks (2 cycles) until surgery, progression, unacceptable toxicity or discontinuation from the study treatment for any other reason.
Subjects were randomized in a 2:2:1 ratio to one of the 3 treatment arms (canakinumab alone or canakinumab in combination with pembrolizumab or pembrolizumab alone). Surgery was performed between 4 to 6 weeks after the first dose of study treatment.
All randomized subjects were followed for safety for up to 130 days following the last dose of study treatment (safety follow-up period).
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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Canakinumab monotherapy
Participants received 200 mg of canakinumab once every 3 weeks for a maximum duration of 6 weeks prior to surgery
干预措施: Canakinumab (Drug)
Canakinumab + pembrolizumab
Participants received 200 mg of canakinumab in combination with 200 mg of pembrolizumab once every 3 weeks for a maximum duration of 6 weeks prior to surgery
干预措施: Canakinumab (Drug)
Canakinumab + pembrolizumab
Participants received 200 mg of canakinumab in combination with 200 mg of pembrolizumab once every 3 weeks for a maximum duration of 6 weeks prior to surgery
干预措施: Pembrolizumab (Drug)
Pembrolizumab monotherapy
Participants received 200 mg of pembrolizumab every 3 weeks for a maximum duration of 6 weeks prior to surgery
干预措施: Pembrolizumab (Drug)
结局指标
主要结局
Major Pathological Response (MPR) Rate at the Time of Surgery in Subjects Randomized to Canakinumab Monotherapy and in Combination With Pembrolizumab Based on Central Review
时间窗: At time of surgery (up to 6 weeks after first dose of study treatment)
MPR was defined as the percentage of participants with major pathological response (defined as ≤10% residual viable tumor cells on surgical samples). Any participant who had \>10% residual viable cancer cells, or started new antineoplastic therapy prior to surgery, or did not have the surgery performed, or had the surgery performed but with unevaluable MPR result, was considered as a non-responder. MPR was assessed at the time of surgery in all subjects randomized to canakinumab monotherapy and in combination with pembrolizumab based on central review.
次要结局
- Surgical Feasibility Rate(Up to 6 weeks after first dose)
- Canakinumab Antidrug Antibodies (ADA) Prevalence(Predose (0 hour) on Day 1 of Cycle 1 (Cycle=21 days))
- Pembrolizumab ADA Prevalence(Predose (0 hour) on Day 1 of Cycle 1 (Cycle = 21 days))
- Canakinumab ADA Incidence(From baseline (Predose on Day 1 of Cycle 1) up to 130 days after last dose of study treatment (assessed up to 24.6 weeks). Cycle = 21 days)
- Serum Canakinumab Concentration(Predose (0 hour) on Day 1 of Cycles 1 and 2 (Cycle =21 days))
- Serum Pembrolizumab Concentration(Predose (0 hour) and 0.5 hours post dose on Day 1 of Cycle 1 and predose on Cycle 2 (Cycle =21 days))
- Major Pathological Response (MPR) Rate Based on the Levels of Biomarkers(From date of randomization up to 6 weeks after first dose)
- Pembrolizumab ADA Incidence(From baseline (Predose on Day 1 of Cycle 1) up to 26 days after last dose of study treatment (assessed up to 10.7 weeks). Cycle = 21 days)
- Overall Response Rate (ORR) Based on Local Investigator Assessment Using RECIST v1.1(From date of randomization to date of surgery, assessed up to 6 weeks)
- Major Pathological Response (MPR) Rate at the Time of Surgery in Subjects Randomized to Pembrolizumab Monotherapy Based on Central Review(At time of surgery (up to 6 weeks after first dose))
- Difference in Major Pathological Response (MPR) Rate Between the Canakinumab Plus Pembrolizumab Arm and the Pembrolizumab Arm Based on Central Review(At time of surgery (up to 6 weeks after first dose of study treatment))
- Major Pathological Response (MPR) Rate at the Time of Surgery in All Subjects Based on Local Review(At time of surgery (up to 6 weeks after first dose))