A Phase 3 Randomized, Controlled Study of IMC-F106C Plus Nivolumab Versus Nivolumab Regimens in HLA-A*02:01-Positive Participants With Previously Untreated Advanced Melanoma (PRISM-MEL-301
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 680
- 试验地点
- 374
- 主要终点
- Progression-Free Survival (PFS)
研究概览
简要总结
This is a phase 3, randomized, controlled study of brenetafusp (IMC-F106C) plus nivolumab compared to standard nivolumab regimens in HLA-A*02:01-positive participants 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
- •Participants must be HLA-A*02:01-positive
- •Participants must have histologically confirmed Stage IV or unresectable Stage III melanoma
- •Archived or fresh tumor tissue sample that must be confirmed as adequate
- •Participants must have measurable disease per RECIST 1.1
- •Participant must have BRAF V600 mutation status determined
- •Participants must have an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1
- •Male and female participants of childbearing potential who are sexually active with a non-sterilized partner must agree to use highly effective methods of birth control from the study screening date until 5 months after the final dose of study intervention
排除标准
- •Participants with a history of a malignant disease other than those being treated in this study
- •Participants with untreated, active, or symptomatic central nervous system (CNS) metastases or carcinomatous meningitis
- •Hypersensitivity to IMC-F106C, nivolumab, relatlimab, or any associated excipients
- •Participants with clinically significant pulmonary disease or impaired lung function
- •Participants with clinically significant cardiac disease or impaired cardiac function
- •Participants with active autoimmune disease requiring immunosuppressive treatment
- •Participants with any medical condition that is poorly controlled or that would, in the Investigator's or Sponsor's judgment, adversely impact the participant's participation in the clinical study due to safety concerns, compliance with clinical study procedures, or interpretation of study results
- •Participants who received prior systemic anticancer therapy for unresectable or metastatic melanoma
- •Participants with a history of a life-threatening AE related to prior anti-PD-(L)1 or anti-LAG-3
研究组 & 干预措施
Arm A: Brenetafusp Low Dose + Nivolumab
Participants receive brenetafusp Low Dose once weekly (QW) for the first 13 weeks, then every 2 weeks (Q2W) through Week 51, and then every 4 weeks (Q4W). Nivolumab is given Q4W.
Closed to randomization after dose recommendation by the IDMC in November 2025.
干预措施: Brenetafusp (Drug)
Arm A: Brenetafusp Low Dose + Nivolumab
Participants receive brenetafusp Low Dose once weekly (QW) for the first 13 weeks, then every 2 weeks (Q2W) through Week 51, and then every 4 weeks (Q4W). Nivolumab is given Q4W.
Closed to randomization after dose recommendation by the IDMC in November 2025.
干预措施: Nivolumab (Drug)
Arm B: Brenetafusp High Dose + Nivolumab
Participants receive brenetafusp High Dose once weekly (QW) for the first 13 weeks, then every 2 weeks (Q2W) through Week 51, and then every 4 weeks (Q4W). Nivolumab is given Q4W.
Selected as go-forward experimental arm after dose recommendation by the IDMC in November 2025
干预措施: Brenetafusp (Drug)
Arm B: Brenetafusp High Dose + Nivolumab
Participants receive brenetafusp High Dose once weekly (QW) for the first 13 weeks, then every 2 weeks (Q2W) through Week 51, and then every 4 weeks (Q4W). Nivolumab is given Q4W.
Selected as go-forward experimental arm after dose recommendation by the IDMC in November 2025
干预措施: Nivolumab (Drug)
Arm C: Nivolumab OR Nivolumab + Relatlimab
Participants receive nivolumab 480 mg monotherapy, or nivolumab 480 mg + relatlimab 160 mg, Q4W.
干预措施: Nivolumab (Drug)
Arm C: Nivolumab OR Nivolumab + Relatlimab
Participants receive nivolumab 480 mg monotherapy, or nivolumab 480 mg + relatlimab 160 mg, Q4W.
干预措施: Nivolumab + Relatlimab (Drug)
结局指标
主要结局
Progression-Free Survival (PFS)
时间窗: Up to ~45 months
PFS as assessed by blinded independent central review (BICR) according to Response Evaluation Criteria in Solid Tumours (RECIST 1.1).
次要结局
- Number of Participants Experiencing a Dose Interruption, Reduction, or Discontinuation(Up to ~45 months)
- Maximum Plasma Concentration (Cmax) of IMC-F106C(Day 1 of Weeks 1, 2, and 3: Predose and 0.5 and 4 hours postdose)
- Incidence of anti-IMC-F106C Antibodies(Up to ~45 months)
- Association between PFS and Intra-Tumor Immune Cells(Up to ~45 months)
- Health-Related Quality of Life(Up to ~45 months)
- Overall Survival (OS)(Up to ~57 months)
- Overall Response Rate (ORR)(Up to ~45 months)
- Number of Participants Experiencing ≥1 Adverse Event (AE)(Up to ~57 months)
- Number of Participants Experiencing ≥1 Serious Adverse Event (SAE)(Up to ~57 months)