A Phase II, Open-Label, Multicenter, Randomized Study of the Efficacy and Safety of RO7198457 in Combination With Pembrolizumab Versus Pembrolizumab in Patients With Previously Untreated Advanced Melanoma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 131
- 试验地点
- 41
- 主要终点
- Progression-free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v.1.1) After Randomization
研究概览
简要总结
This study will evaluate the efficacy, safety, pharmacokinetics, and patient-reported outcomes (PROs) of autogene cevumeran (RO7198457) plus pembrolizumab compared with pembrolizumab alone in patients with previously untreated advanced melanoma.
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
- •Histologically confirmed metastatic (recurrent or de novo Stage IV) or unresectable locally advanced (Stage IIIC or IIID) cutaneous, acral, or mucosal melanoma;
- •Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1;
- •Life expectancy >/= 12 weeks;
- •Adequate hematologic and end-organ function;
- •Naive to prior systemic anti-cancer therapy for advanced melanoma with some exceptions;
- •Tumor specimen availability;
- •Measurable disease per RECIST v1.1.
排除标准
- •Ocular/uveal melanoma;
- •Any anti-cancer therapy with the exceptions as specified in the protocol;
- •Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases;
- •Previous splenectomy;
- •History of autoimmune disease;
- •Prior allogeneic bone marrow transplantation or prior solid organ transplantation;
- •Positive test for Human Immunodeficiency Virus (HIV) infection;
- •Active hepatitis B or C or tuberculosis;
- •Significant cardiovascular disease;
- •Known clinically significant liver disease.
研究组 & 干预措施
Safety Run-in Period: Autogene Cevumeran + Pembrolizumab
Participants will receive at least one cycle of 200 mg pembrolizumab monotherapy by intravenous (IV) infusion followed by 200 mg pembrolizumab IV infusion every 3 weeks (Q3W) plus a recommended dose of autogene cevumeran.
干预措施: Autogene cevumeran (Biological)
Safety Run-in Period: Autogene Cevumeran + Pembrolizumab
Participants will receive at least one cycle of 200 mg pembrolizumab monotherapy by intravenous (IV) infusion followed by 200 mg pembrolizumab IV infusion every 3 weeks (Q3W) plus a recommended dose of autogene cevumeran.
干预措施: Pembrolizumab (Drug)
Randomized Period: Arm A: Pembrolizumab
Participants will receive 200 mg pembrolizumab administered by IV infusion Q3W. Participants in Arm A have the option to cross over to combination treatment with autogene cevumeran plus pembrolizumab (Arm B) after confirmed disease progression.
干预措施: Pembrolizumab (Drug)
Randomized Period: Arm B: Autogene Cevumeran + Pembrolizumab
Participants will receive at least one cycle of 200 mg pembrolizumab monotherapy by IV infusion followed by 200 mg pembrolizumab IV infusion Q3W plus a recommended dose of autogene cevumeran.
干预措施: Autogene cevumeran (Biological)
Randomized Period: Arm B: Autogene Cevumeran + Pembrolizumab
Participants will receive at least one cycle of 200 mg pembrolizumab monotherapy by IV infusion followed by 200 mg pembrolizumab IV infusion Q3W plus a recommended dose of autogene cevumeran.
干预措施: Pembrolizumab (Drug)
结局指标
主要结局
Progression-free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v.1.1) After Randomization
时间窗: From randomization to PD or death (up to approximately 60 months)
PFS was defined as the time from randomization to the first documented PD as determined by the investigator according to RECIST v1.1 or death from any cause, whichever occurred first. PD was defined as at least a 20% increase in the sum of diameters (SOD) of target lesions, taking as reference the smallest sum on study (nadir), including baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeters (mm). Kaplan-Meier (KM) method was used to estimate median PFS.
次要结局
- Objective Response Rate (ORR) According to RECIST V.1.1 After Randomization(Up to approximately 60 months)
- Overall Survival (OS) After Randomization(From randomization to death (up to approximately 63 months))
- Duration of Response (DOR) According to RECIST V.1.1 After Randomization(Up to approximately 60 months)
- Change From Baseline in Global Health Status (GHS)/Health-related Quality of Life (HRQoL) Score Assessed by European Organisation for Research and Treatment of Cancer 30-Item Quality of Life Questionnaire (EORTC QLQ-C30)(Baseline, Day 1 of Cycles 1 to 34, time of first PD, time to last dose, treatment discontinuation and study drug completion (up to approximately 29 months) (1 cycle = 21 days))
- ORR According to RECIST V.1.1 After Crossover(Up to 54.7 months)
- Number of Participants With Adverse Events (AEs)(Baseline up to 90 days after the final dose of study drug (Safety run-in and randomized stage: up to 32 months; Cross-over stage: up to 24 months))