Phase II Multicenter Randomized Two-arm Study of Capmatinib and Spartalizumab Combination Therapy vs Docetaxel in Pretreated Adult Patients With EGFR Wild-type ALK Rearrangement Negative Advanced/Metastatic Non-small Cell Lung Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 18
- 试验地点
- 2
- 主要终点
- Run-in Part: Relative Dose Intensity Received by Participants
研究概览
简要总结
The purpose of this trial was to evaluate the safety and efficacy of capmatinib in combination with spartalizumab in adult participants with epidermal growth factor receptor (EGFR) wild type (for exon 19 deletions and exon 21 L858R substitution mutations), anaplastic lymphoma kinase (ALK) rearrangement negative in locally advanced (stage IIIB, not eligible for definitive chemo-radiation) or metastatic (stage IV) Non-small cell lung cancer (NSCLC) after failure of platinum doublet and checkpoint inhibitor treatment.
详细描述
This was a two-part prospectively designed, multicenter, open-label, randomized phase II study.
Part 1: Run-in. Prior to the randomized part of the study, a run-in to assess the safety and tolerability as well as preliminary efficacy of the capmatinib and spartalizumab combination was conducted. Participants were treated with capmatinib 400 mg twice daily (BID) and spartalizumab 400 mg intravenously (i.v.) once every 28 days. A review was planned to take place after all participants had at least 24 weeks of follow-up. The decision to expand the study to the randomized part was to be based on the safety, tolerability, and preliminary efficacy of the capmatinib and spartalizumab combination.
Part 2: Randomized. Subjects were planned to be randomized to one of the following arms in a 2:1 ratio: 1) combination of capmatinib 400 mg BID and spartalizumab 400 mg i.v. once every 28 days; 2) docetaxel 75 mg/m2 i.v. following local guidelines as per standard of care and product labels. Based on the results obtained in the run-in part of the study, the randomized part was not opened.
For the run-in part of the study, the treatment period began on Cycle 1 Day 1 and continued in 28-day cycles until disease progression, unacceptable toxicity, withdrawal of informed consent, pregnancy, lost to follow-up, or death irrespective of start of new anti-neoplastic therapy. After treatment discontinuation, all subjects were followed for safety evaluations during the safety follow-up period, and the subject's status was collected every 8 weeks as part of the survival follow-up
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •Histologically confirmed locally advanced/metastatic (stage IIIB/IV), EGFR wild-type, ALK rearrangement negative, non-small cell lung cancer
- •Subject had demonstrated progression following one prior platinum doublet and one prior PD-(L)1 checkpoint inhibitor (either alone or in combination, the most recent treatment regimen must have contained a PD-(L)1 checkpoint inhibitor)
- •Subjects must be candidates for single agent docetaxel
- •Subjects must have at least one lesion evaluable by RECIST 1.1
排除标准
- •Prior treatment with a MET inhibitor or HGF (Hepatocyte growth factor) targeting therapy
- •Any untreated central nervous system (CNS) lesion
- •Use of any live vaccines against infectious diseases within 12 weeks of initiation of study treatment.
- •Other protocol-defined inclusion/exclusion criteria might apply.
研究组 & 干预措施
Run-in part: capmatinib + spartalizumab
Participants (enrolled in the run-in part) were treated with capmatinib 400 mg twice daily (BID) and spartalizumab 400 mg intravenously (i.v.) once every 28 days
干预措施: Capmatinib (Drug)
Run-in part: capmatinib + spartalizumab
Participants (enrolled in the run-in part) were treated with capmatinib 400 mg twice daily (BID) and spartalizumab 400 mg intravenously (i.v.) once every 28 days
干预措施: Spartalizumab (Drug)
Randomized part: capmatinib+spartalizumab
Participants (enrolled in the randomized part) treated with capmatinib 400 mg twice daily (BID) and spartalizumab 400 mg intravenously (i.v.) once every 28 days
干预措施: Capmatinib (Drug)
Randomized part: capmatinib+spartalizumab
Participants (enrolled in the randomized part) treated with capmatinib 400 mg twice daily (BID) and spartalizumab 400 mg intravenously (i.v.) once every 28 days
干预措施: Spartalizumab (Drug)
Randomized part: docetaxel
Participants (enrolled in the randomized part) treated with docetaxel 75mg/m2 i.v. following local guidelines as per standard of care and product labels once every 21 days
干预措施: Docetaxel (Drug)
结局指标
主要结局
Run-in Part: Relative Dose Intensity Received by Participants
时间窗: From the day of the first dose of study medication to end of treatment, assessed up to maximum duration of 68 weeks
The relative dose intensity of capmatinib and spartalizumab is computed as the ratio of dose intensity and planned dose intensity, multiplied by 100.
Run-in Part: Percentage of Participants With Dose Limiting Toxicities (DLTs)
时间窗: From the day of the first dose of study medication up to 56 days
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.
Run-in Part: Percentage of Participants With at Least One Dose Interruption
时间窗: From the day of the first dose of study medication to end of treatment, assessed up to maximum duration of 68 weeks
Percentage of participants with at least one dose interruption. Dose interruptions were allowed for capmatinib and spartalizumab.
Randomized Part: Overall Survival (OS)
时间窗: From start of treatment to death due to any cause, assessed until the end of the study (up to a planned duration of 18 months)
OS is defined as the time from date of start of treatment to date of death due to any cause. If a participant was not known to have died, survival was censored at the date of last known date patient alive. Results are not available because randomized part never started.
Run-in Part: Percentage of Participants With Adverse Events (AEs)
时间窗: From the day of the first dose of study medication to 150 days after the last dose of spartalizumab, or 30 days after the last dose of capmatinib (whichever is later) up to maximum duration of approximately 1.7 years
Percentage of participants with AEs, including changes from baseline in vital signs and laboratory results qualifying and reported as AEs. AEs were assessed and graded according to the Common Terminology Criteria for Adverse Events (CTCAE) v5.0: Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences; Grade 5: Death
Run-in Part: Percentage of Participants With at Least One Dose Reduction.
时间窗: From the day of the first dose of study medication to end of treatment, assessed up to maximum duration of 68 weeks
Percentage of participants with at least one dose reduction. Dose reductions were only allowed for capmatinib
次要结局
- Duration of Response (DOR) Based on RECIST 1.1 and as Per Investigator Assessment(From first documented response (CR or PR) to first documented progression or death, whichever came first, assessed up to 68 weeks (run-in part))
- Maximum Plasma Concentration (Cmax) of Capmatinib(Cycle 3 day 1 at predose, 0.5 hours (h), 1h, 2h, 4h and 8h postdose. Each Cycle is 28 days)
- AUClast of Capmatinib(Cycle 3 day 1 at predose, 0.5 hours (h), 1h, 2h, 4h and 8h postdose. Each Cycle is 28 days)
- AUCtau of Capmatinib(Cycle 3 day 1 at predose, 0.5 hours (h), 1h, 2h, 4h and 8h postdose. Each Cycle is 28 days)
- Objective Response Rate (ORR) Based on RECIST 1.1 and as Per Investigator Assessment(From start of treatment until end of treatment, assessed up to 68 weeks (run-in part))
- Progression Free Survival (PFS)(From start of treatment until the first documented radiological progression or death, whichever comes first, assessed up to 68 weeks (run-in part))
- AUClast of Spartlizumab(CCycle 3 day 1 at predose and 1 hour postdose (up to 1.53 hours postdose), cycle 3 day 4 (=72 hours postdose), cycle 3 day 8 (=168 hours postdose) and cycle 3 day 15 (=336 hours postdose). Each Cycle is 28 days)
- Time to Reach Maximum (Tmax) Plasma Concentration of Spartlizumab(Cycle 3 day 1 at predose and 1 hour postdose (up to 1.53 hours postdose), cycle 3 day 4 (=72 hours postdose), cycle 3 day 8 (=168 hours postdose) and cycle 3 day 15 (=336 hours postdose). Each Cycle is 28 days)
- Disease Control Rate (DCR) Based on RECIST 1.1 and as Per Investigator Assessment(From start of treatment until end of treatment, assessed up to 68 weeks (run-in part))
- Time to Response (TTR) Based on RECIST 1.1 and as Per Investigator Assessment(From start of treatment to the first documented response of either complete response or partial response, assessed up to 68 weeks (run-in part))
- Time to Reach Maximum (Tmax) Plasma Concentration of Capmatinib(Cycle 3 day 1 at predose, 0.5 hours (h), 1h, 2h, 4h and 8h postdose. Each Cycle is 28 days)
- AUCtau of Spartlizumab(Cycle 3 day 1 at predose and 1 hour postdose (up to 1.53 hours postdose), cycle 3 day 4 (=72 hours postdose), cycle 3 day 8 (=168 hours postdose) and cycle 3 day 15 (=336 hours postdose). Each Cycle is 28 days)
- Spartalizumab ADA Incidence On-treatment(Predose at Cycle (C)1 Day (D)1, C2D1, C3D1, C4D1, C6D1, C8D1, C10D1, C12D1, thereafter every 6 cycles until discontinuation, and end of treatment (EOT), 30-day and 150-day after EOT)
- Maximum Plasma Concentration (Cmax) of Spartlizumab(Cycle 3 day 1 at predose and 1 hour postdose (up to 1.53 hours postdose), cycle 3 day 4 (=72 hours postdose), cycle 3 day 8 (=168 hours postdose) and cycle 3 day 15 (=336 hours postdose). Each Cycle is 28 days)
- Spartalizumab Antidrug Antibodies (ADA) Prevalence at Baseline(Cycle 1 Day 1 at predose. Each Cycle is 28 days)