Phase 2/3 Randomized Study of Tebentafusp as Monotherapy and in Combination With Pembrolizumab Versus Investigator's Choice in HLA-A*02:01-positive Participants With Previously Treated Advanced Melanoma (TEBE-AM)
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 540
- 试验地点
- 115
- 主要终点
- Overall Survival (OS)
研究概览
简要总结
The purpose of this study is to evaluate the efficacy and safety of tebentafusp-based regimens, including tebentafusp monotherapy and in combination with anti-PD1 vs investigator choice (including clinical trials of investigational agents, salvage therapy per local standard of care [SoC], best supportive care [BSC] on protocol survivor follow up) in patients with advanced non-ocular melanoma.
详细描述
This is a phase 3 (as upon conversion to phase 3 there were no changes to the arms listed herein), multicenter, open-label study to evaluate the efficacy and safety of tebentafusp as monotherapy (Arm A) and in combination with pembrolizumab (Arm B) compared with standard of care or best supportive care (Arm C) in participants with non-ocular advanced melanoma who have progressed on a prior anti-PD(L)1 regimen, received an approved anti-CTLA4 regimen and, if the participant has a BRAF mutation, a prior BRAF tyrosine kinase inhibitor (TKI) regimen.
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
- •HLA-A*02:01-positive
- •unresectable Stage III or Stage IV non-ocular melanoma
- •archival tumor tissue sample or a newly obtained biopsy of a tumor lesion not previously irradiated has been provided.
- •measurable or non-measurable disease per RECIST 1.1
- •Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1
- •If applicable, must agree to use highly effective contraception
- •Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the Informed Consent (ICF) and protocol
- •Must agree to provide protocol specified samples for biomarker analyses.
排除标准
- •Pregnant or lactating women
- •diagnosis of ocular or metastatic uveal melanoma
- •history of a malignant disease other than those being treated in this study
- •ineligible to be retreated with pembrolizumab due to a treatment-related AE
- •known untreated or symptomatic central nervous system (CNS) metastases and/or carcinomatous meningitis
- •previous severe hypersensitivity reaction to treatment with another monoclonal antibody (mAb)
- •active autoimmune disease requiring immunosuppressive treatment
- •known psychiatric or substance abuse disorders
- •received prior treatment with a licensed or investigative Immune-mobilizing monoclonal T-cell receptor Against Cancer (ImmTAC) medication or who have not completed adequate washout from prior medications.
- •received chemotherapy or biological cancer therapy (excluding anti-PD(L)1 mAb, ipilimumab, and BRAF TKI regimen) within 14 days of first dose
- •received cellular therapies within 90 days of study intervention
- •ongoing Common Terminology Criteria for Adverse Events(CTCAE) Grade ≥ 2 clinically significant who in the opinion of the investigator could affect the outcome of the study
- •received systemic treatment with steroids or any other immunosuppressive drug within 2 weeks of first dose
- •have not progressed on treatment with an anti-PD(L)1 mAb
- •have not received prior treatment with an approved anti-CTLA-4 mAb
- •have a BRAF V600 mutation, who have not received a prior BRAF/MEK TKI regimen
- •currently participating or have participated in a study of an investigational agent or using an investigational device within 30 days of the first dose
- •known history of chronic viral infections such as hepatitis B virus (HBV) or hepatitis C virus (HCV)
- •known clinically significant pulmonary or cardiac disease or impaired lung or cardiac function
- •Out of range Laboratory values
- •history of allogenic tissue/solid organ transplant
研究组 & 干预措施
Arm A: Tebentafusp Monotherapy
Participants receive tebentafusp as single agent.
干预措施: Tebentafusp (Drug)
Arm B: Tebentafusp + Pembrolizumab
Participants receive tebentafusp in combination with pembrolizumab.
干预措施: Tebentafusp with Pembrolizumab (Drug)
Arm C: Investigator's Choice
Participants receive investigator's choice of therapy.
干预措施: Investigators Choice (Drug)
结局指标
主要结局
Overall Survival (OS)
时间窗: Up to ~4 years
OS is the time from randomization to death due to any cause.
次要结局
- Change from Baseline in Circulating Tumor DNS (ctDNA)(Up to ~9 weeks)
- Number of participants with ≥1 adverse event (AE)(Up to ~4 years)
- Number of participants with ≥1 serious adverse event (SAEs)(Up to ~4 years)
- Number of participants with dose interruptions, reductions, and discontinuations from study therapy due to AEs(Up to ~4 years)
- Number of participants with Grade ≥2 cytokine release syndrome (CRS)(Up to ~4 years)
- Responses to the EORTC Core Quality of Life (EORTC-QLQ-C30)(At designated time points up to ~4 years)
- Responses to the European Quality of Life 5 Dimensions 5 Level Version (EQ-5D-5L)(At designated time points up to ~4 years)
- Plasma Concentration of Tebentafusp(At designated time points up to ~4 years)
- Number of participants with anti-tebentafusp antibodies(At designated time points up to ~4 years)