A Randomized, Open-label, Phase II Open Platform Study Evaluating the Efficacy and Safety of Novel Spartalizumab (PDR001) Combinations in Previously Treated Unresectable or Metastatic Melanoma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 196
- 试验地点
- 7
- 主要终点
- Overall Response Rate (ORR)
研究概览
简要总结
The primary purpose of this study is to evaluate the efficacy of novel spartalizumab (PDR001) combinations in previously treated unresectable or metastatic melanoma
详细描述
This study was a randomized, open-label, two-part, multi-center, open platform phase II study designed to evaluate the efficacy and safety of the anti-PD-1 antibody PDR001 in combination with novel agents for previously treated unresectable or metastatic melanoma. Additionally, a non-randomized single-arm was added based on interim analysis findings to assess the efficacy and safety of PDR001 in combination with LAG525 in subjects with previously treated unresectable or metastatic LAG-3 positive melanoma.
The study consisted of two parts: the selection part and the expansion part, which were applicable to both the randomized and non-randomized sections. In the randomized section, participants were randomized to one of four combination arms available for enrollment:
- Arm 1: LAG525 600 mg intravenously (i.v.) every 4 weeks (Q4W) and PDR001 400 mg i.v. Q4W.
- Arm 2: INC280 400 mg orally (p.o.) twice daily (BID) and PDR001 400 mg i.v. Q4W.
- Arm 3: ACZ885 300 mg subcutaneously (s.c.) every 4 weeks (Q4W) and PDR001 400 mg i.v. Q4W.
- Arm 4: LEE011 600 mg p.o. once daily (QD) on Days 1-21 of a 28-day cycle and PDR001 400 mg i.v. Q4W.
At each interim analysis, the following determinations were made: (1) which arm met the pre-specified efficacy criteria and expanded to the expansion part, (2) which arms continued enrollment in selection part (up to 45 subjects), and (3) which arms were discontinued due to futility, considering efficacy, safety, and biomarker data. The expansion phase included enrollment of subjects only in the combination arms that met the pre-specified criteria in selection part.
In the non-randomized section, a single combination arm was opened for enrollment in selection part:
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
盲法说明
After approval of protocol amendment 5 (26Jun2020), a non-randomized single arm was added
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
Arm 1: LAG525 + PDR001 (randomized section)
Participnats randomized to receive LAG525 at a dosage of 600 mg administered intravenously every 4 weeks, in combination with PDR001 at a dosage of 400 mg administered intravenously every 4 weeks
干预措施: PDR001 (Drug)
Arm 1: LAG525 + PDR001 (randomized section)
Participnats randomized to receive LAG525 at a dosage of 600 mg administered intravenously every 4 weeks, in combination with PDR001 at a dosage of 400 mg administered intravenously every 4 weeks
干预措施: LAG525 (Drug)
Arm 2: INC280+PDR001 (randomized section)
Participants randomized to receive INC280 orally at a dosage of 400 mg twice daily, in combination with PDR001 intravenously at a dosage of 400 mg every 4 weeks
干预措施: PDR001 (Drug)
Arm 2: INC280+PDR001 (randomized section)
Participants randomized to receive INC280 orally at a dosage of 400 mg twice daily, in combination with PDR001 intravenously at a dosage of 400 mg every 4 weeks
干预措施: INC280 (Drug)
Arm 3: ACZ885 + PDR001 (randomized section)
Participants randomized to receive to receive ACZ885 at a dosage of 300 mg administered subcutaneously every 4 weeks, in combination with PDR001 at a dosage of 400 mg administered intravenously every 4 weeks
干预措施: PDR001 (Drug)
Arm 3: ACZ885 + PDR001 (randomized section)
Participants randomized to receive to receive ACZ885 at a dosage of 300 mg administered subcutaneously every 4 weeks, in combination with PDR001 at a dosage of 400 mg administered intravenously every 4 weeks
干预措施: ACZ885 (Drug)
Arm 4: LEE011 + PDR001 (randomized section)
Participants randomized to receive LEE011 orally at a dosage of 600 mg once daily on Days 1-21 of a 28-day cycle, in combination with PDR001 intravenously at a dosage of 400 mg every 4 weeks
干预措施: PDR001 (Drug)
Arm 4: LEE011 + PDR001 (randomized section)
Participants randomized to receive LEE011 orally at a dosage of 600 mg once daily on Days 1-21 of a 28-day cycle, in combination with PDR001 intravenously at a dosage of 400 mg every 4 weeks
干预措施: LEE011 (Drug)
Arm 1A: LAG525 + PDR001 (non-randomized section)
LAG-3 positive participants received LAG525 at a dosage of 600 mg administered intravenously every 4 weeks, in combination with PDR001 at a dosage of 400 mg administered intravenously every 4 weeks
干预措施: PDR001 (Drug)
Arm 1A: LAG525 + PDR001 (non-randomized section)
LAG-3 positive participants received LAG525 at a dosage of 600 mg administered intravenously every 4 weeks, in combination with PDR001 at a dosage of 400 mg administered intravenously every 4 weeks
干预措施: LAG525 (Drug)
结局指标
主要结局
Overall Response Rate (ORR)
时间窗: Up to 49 months (randomized section) and 18 months (non-randomized section)
ORR defined as the percentage of patients with a best overall response of either confirmed complete response (CR) or partial response (PR) as per local review by Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) and assessed by computed tomography (CT)/ magnetic resonance imaging (MRI). CR:Disappearance of all non-nodal target and non-target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.
次要结局
- Disease Control Rate (DCR)(Up to 49 months (randomized section) and 18 months (non-randomized section))
- Percentage of Participants With ACZ885 Anti-drug Antibodies (ADA) Positive Result at Baseline(At Baseline)
- Percentage of Participants With PDR001 Anti-drug Antibodies (ADA) Positive Result at Baseline(At Baseline)
- Overall Survival (OS)(From randomization (or start of treatment for non-randomized section) to death due to any cause, assessed up to 49 months (randomized section) and 24 months (non-randomized section))
- Progression Free Survival (PFS)(From randomization (or start of treatment for non-randomized section) to disease progression or death due to any cause, whichever occurs first, assessed up to 49 months (randomized section) and 18 months (non-randomized section))
- Duration of Response (DOR)(From first documented response to disease progression or death due to any cause, whichever occurs first, assessed up to 49 months (randomized part) and 18 months (non-randomized part))
- Percentage of Participants Who Were Treatment-induced ADA Positive and Treatment-boosted ADA Positive for PDR001(Pre-infusion on Day 1 of Cycle 1, 2, 3, 4, 5, 6 and thereafter every 3 cycles until end of treatment (EOT), EOT, and 30 and 150 days post-EOT (assessed up to 49 months randomized section and 24 months non-randomized section). Cycle= 28 days)
- Percentage of Participants With LAG525 Anti-drug Antibodies (ADA) Positive Result at Baseline(At Baseline)
- Percentage of Participants Who Were Treatment-induced ADA Positive and Treatment-boosted ADA Positive for LAG525(Pre-infusion on Day 1 of Cycle 1, 2, 3, 4, 5, 6 and thereafter every 3 cycles until end of treatment (EOT) and EOT (assessed up to 49 months in the randomized section and 18 months in the non-randomized section). Cycle= 28 days)
- Percentage of Participants Who Were Treatment-induced ADA Positive and Treatment-boosted ADA Positive for ACZ885(Pre-infusion on Day 1 of Cycle 1, 2, 3, 4, 5, 6 and thereafter every 3 cycles until end of treatment (EOT) and EOT (assessed up to 40 months). Cycle= 28 days)
- Percentage of Participants With a Favorable Biomarker Profile (pFBP)(Baseline and after 3-4 weeks of treatment)