A Phase Ib/II, Open-Label, Multicenter, Randomized Umbrella Study Evaluating the Efficacy and Safety of Multiple Treatment Combinations in Patients With Melanoma (Morpheus-Melanoma)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 110
- 试验地点
- 14
- 主要终点
- Pathologic Response Rate (pRR) for Cohort 1 as Determined by Independent Pathologic Review
研究概览
简要总结
This study will evaluate the efficacy, safety, and pharmacokinetics of treatment combinations in cancer immunotherapy (CIT)-naive participants with resectable Stage III melanoma (Cohort 1) and in participants with Stage IV melanoma (Cohort 2). The study is designed with the flexibility to open new treatment arms as new treatments become available, close existing treatment arms that demonstrate minimal clinical activity or unacceptable toxicity, and modify the participant population.
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
Cohort 1: Nivolumab + Ipilimumab
Cohort 1 participants in the nivolumab plus ipilimumab arm will receive treatment for 2 cycles (6 weeks) on Day 1 of each cycle (cycle length 21 days) until surgery, or until unacceptable toxicity or loss of clinical benefit, whichever occurs first.
干预措施: Nivolumab (Drug)
Cohort 1: Nivolumab + Ipilimumab
Cohort 1 participants in the nivolumab plus ipilimumab arm will receive treatment for 2 cycles (6 weeks) on Day 1 of each cycle (cycle length 21 days) until surgery, or until unacceptable toxicity or loss of clinical benefit, whichever occurs first.
干预措施: Ipilimumab (Drug)
Cohort 1: RO7247669 2100 mg
Cohort 1 participants in the RO7247669 arm will receive treatment for 2 cycles (6 weeks) until surgery, or until unacceptable toxicity or loss of clinical benefit, whichever occurs first.
干预措施: RO7247669 2100 mg (Drug)
Cohort 1: + Atezolizumab + Tiragolumab
Cohort 1 participants in the atezolizumab plus tiragolumab arm will receive treatment for 2 cycles (6 weeks) until surgery, or until unacceptable toxicity or loss of clinical benefit, whichever occurs first.
干预措施: Atezolizumab (Drug)
Cohort 1: + Atezolizumab + Tiragolumab
Cohort 1 participants in the atezolizumab plus tiragolumab arm will receive treatment for 2 cycles (6 weeks) until surgery, or until unacceptable toxicity or loss of clinical benefit, whichever occurs first.
干预措施: Tiragolumab (Drug)
Cohort 1: RO7247669 2100 mg + Tiragolumab
Cohort 1 participants in the RO7247669 plus tiragolumab arm will receive treatment for 2 cycles (6 weeks) until surgery, or until unacceptable toxicity or loss of clinical benefit, whichever occurs first.
干预措施: RO7247669 2100 mg (Drug)
Cohort 1: RO7247669 2100 mg + Tiragolumab
Cohort 1 participants in the RO7247669 plus tiragolumab arm will receive treatment for 2 cycles (6 weeks) until surgery, or until unacceptable toxicity or loss of clinical benefit, whichever occurs first.
干预措施: Tiragolumab (Drug)
Cohort 2: RO7247669 2100 mg + Tiragolumab
Cohort 2 participants in RO7247669 plus tiragolumab arm will receive treatment until unacceptable toxicity or loss of clinical benefit as determined by the investigator after an integrated assessment of radiographic and biochemical data, local biopsy results (if available), and clinical status.
干预措施: RO7247669 2100 mg (Drug)
Cohort 2: RO7247669 2100 mg + Tiragolumab
Cohort 2 participants in RO7247669 plus tiragolumab arm will receive treatment until unacceptable toxicity or loss of clinical benefit as determined by the investigator after an integrated assessment of radiographic and biochemical data, local biopsy results (if available), and clinical status.
干预措施: Tiragolumab (Drug)
Cohort 1: RO7247669 600 mg
Cohort 1 participants in the RO7247669 arm will receive treatment for 2 cycles (6 weeks) until surgery, or until unacceptable toxicity or loss of clinical benefit, whichever occurs first.
干预措施: RO7247669 600 mg (Drug)
Cohort 1: RO7247669 600 mg + Tiragolumab
Cohort 1 participants in the RO7247669 plus tiragolumab arm will receive treatment for 2 cycles (6 weeks) until surgery, or until unacceptable toxicity or loss of clinical benefit, whichever occurs first.
干预措施: Tiragolumab (Drug)
Cohort 1: RO7247669 600 mg + Tiragolumab
Cohort 1 participants in the RO7247669 plus tiragolumab arm will receive treatment for 2 cycles (6 weeks) until surgery, or until unacceptable toxicity or loss of clinical benefit, whichever occurs first.
干预措施: RO7247669 600 mg (Drug)
结局指标
主要结局
Pathologic Response Rate (pRR) for Cohort 1 as Determined by Independent Pathologic Review
时间窗: Time of surgery (scheduled at Week 7)
pRR was defined as the percentage of participants with pathologic complete response (pCR), pathologic near complete response (pnCR), and pathologic partial response (pPR) as determined by an independent pathologic review. pCR was defined as a complete absence of viable tumor cells, pnCR as \> 0 to ≤ 10% of viable tumor cells, and pPR was defined as \> 10 to ≤ 50% of viable tumor cells in the dissected lymph node. Participants with missing or no pathologic response assessment, including participants who did not proceed to complete lymph node dissection (CLND), were classified as non-responders. pRR was calculated for each arm along with 95% confidence intervals (CIs) using Clopper-Pearson method. The difference in pRR between the experimental arms and the control arm was calculated, along with 95% CIs using the Wald method with continuity correction.
Objective Response Rate (ORR) for Cohort 2 as Determined by the Investigator
时间窗: From randomization up to approximately 3.6 months
ORR was defined as the percentage of participants with a complete response (CR) or partial response (PR) on two consecutive occasions ≥4 weeks apart, as determined by the investigator according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1). CR was defined as the disappearance of all target lesions or any pathological lymph nodes (whether target or non-target) having a reduction in the short axis to \<10 millimeters (mm). PR was defined as at least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. Participants with missing or no response assessments were classified as non-responders. ORR was calculated for each arm, along with 95% CIs using Clopper-Pearson method.
次要结局
- pRR for Cohort 1 as Determined by Local Pathologic Assessment(Time of surgery ( scheduled at Week 7))
- Event-free Survival (EFS) for Cohort 1(From randomization to disease progression, disease recurrence or death or last tumor assessment (up to 22.51 months))
- Number of Participants With Immune-related AEs Grade ≥ 3 for Cohort 1(From initiation of study treatment up to 135 days after the final dose of study treatment (Up to 5.6 months))
- Rate of Delayed Surgery Due to Treatment-related AEs(Time of surgery (scheduled at Week 7) up to 40.1 weeks)
- Duration of Surgery Delay Due to Treatment-related AEs(Time of surgery (scheduled at Week 7) up to 40.1 weeks)
- Relapse-free Survival (RFS) for Cohort 1(From surgery (scheduled at Week 7) to first documented disease recurrence or death or last tumor assessment (up to 20.9 months))
- Overall Survival (OS) for Cohort 1(From randomization to death from any cause or last known to be alive (Up to 25 months))
- ORR for Cohort 1(Prior to surgery (up to Week 6))
- Number of Participants With Adverse Events (AEs) and Severity of AEs Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0) for Cohort 1(From initiation of study treatment up to 135 days (Serious AEs and AESI) or 30 days (all other AEs) after the final dose of study treatment or until initiation of new systemic anti-cancer therapy (Up to 5.6 months))
- Surgical Complication Rates for Cohort 1(At treatment discontinuation visit (Week 13) and Surgery Follow-Up (6 months after surgery))
- Progression-Free Survival (PFS) for Cohort 2(From randomization/enrollment to first documented disease progression or death or last tumor assessment (up to 3.6 months))
- OS for Cohort 2(From randomization/enrollment to death from any cause or last known to be alive (Up to 24.2 months))
- OS Rates at Specific Timepoints for Cohort 2(Months 3, 6 and 12)
- Duration of Response (DOR) for Cohort 2(Time from the first occurrence of a documented OR to disease progression or death from any cause (up to 3.6 months))
- Disease Control Rate (DCR) for Cohort 2(From randomization up to 3.6 months)
- Number of Participants With AEs and Severity of AEs Determined According to NCI CTCAE v5.0 for Cohort 2(From initiation of study treatment up to 135 days (Serious AEs and AESI) or 30 days (all other AEs) after the final dose of study treatment or until initiation of new systemic anti-cancer therapy (Up to 10 months))