A Randomized, Open-label, Multicenter, Multi-arm, Phase 1b/2 Platform Study to Evaluate Safety and Efficacy of Investigational Immunotherapies in Participants With Previously Treated Unresectable or Metastatic Melanoma
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 试验地点
- 13
- 主要终点
- To identify novel immunotherapy IPs to progress into the expansion part (Selection Part)
研究概览
简要总结
This is a platform study evaluating the safety and efficacy of multiple novel investigational products (IPs) that target unresectable or metastatic cutaneous melanoma in participants who have failed standard treatment.
详细描述
This is a Phase 1b/2, randomized, open label, multicenter, platform study evaluating the safety and efficacy of multiple novel investigational products (IPs) that target mechanisms implicated in resistance to immunotherapy in participants with unresectable or metastatic cutaneous melanoma who have resistance to anti-PD-1/L1 agents. This study will include multiple treatment arms that can be added sequentially or in parallel.
Each arm consists of a selection and expansion part. The selection part is used for evaluation of safety and preliminary efficacy in each arm. The selection part may also include a safety run-in portion for preliminary safety evaluation and dose confirmation prior to proceeding. If the criteria for safety and preliminary efficacy are met, the arm will open for additional enrollment in an expansion phase.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 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
- •Adults, age 18 years or older
- •Histologically confirmed unresectable or metastatic cutaneous melanoma
- •Documented radiological progression on prior treatment(s) that included an anti-PD-1/L1 agent
- •Available tumor tissue OR be willing to provide a fresh tumor biopsy
- •Presence of at least one measurable lesion as assessed by CT and/or MRI according to RECIST 1.1
- •Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0-1
- •Adequate organ and bone marrow function
排除标准
- •Known hypersensitivity to monoclonal antibodies, any of the IPs, or excipients contained in these products
- •Current anti-cancer therapy, other investigational treatment, or any participation in other interventional trials
- •Prior exposure to any therapy that targets the same target as the product under investigation, except for PD-1/L1
- •Known symptomatic/active untreated central nervous system (CNS) metastasis
- •Inadequate recovery from toxicity and/or complications attributable to any previous anti-cancer therapy
- •Inadequate recovery from all recent surgeries
- •At least 1-week from the time of minor surgery and at least 4 weeks from a major surgery
- •Received a live vaccine within 30 days prior to randomization (or planned to receive a live attenuated vaccine during the study)
- •History of HIV infection (positive HIV test, not on antiretroviral therapy, detectable viral load)
- •Active hepatitis B (positive hepatitis B surface antigen test) or hepatitis C infection (positive hepatitis C antibody)
- •Documented history or current diagnosis of clinically significant cardiac disease
- •History of or present CNS disease unrelated to cancer, unless adequately treated with standard medical therapy
- •Received solid organ or bone marrow transplantation
- •History of non-infectious pneumonitis requiring corticosteroid therapy within 1 year prior to enrollment, or current presence of interstitial lung disease
- •Active or previously documented autoimmune disease including but not limited to inflammatory bowel disease, diverticulitis, celiac disease, systemic lupus erythematosus, Wegener syndrome, multiple sclerosis, and vasculitis
- •Requiring long term systemic corticosteroids, except topical cortical steroids for intranasal inhalation or physiological dose
- •Active gastrointestinal (GI) bleeding or GI perforation or fistula
- •Serious active infection requiring intravenous (IV) antibiotics and/or hospitalization at study entry
- •Pregnant or lactating women or women who intend to get pregnant or lactate during the study and up to 120 days after the end of treatment
研究组 & 干预措施
Treatment Arm 1
Sintilimab is a recombinant fully human anti-programmed cell death protein 1 (PD-1) monoclonal antibody, and IBI110 is a recombinant fully human anti-lymphocyte activation gene 3 (LAG3) monoclonal antibody. Sintilimab (IBI308) will be administered intravenously (IV) in combination with IBI110 administered intravenously (IV) every 3-weeks (Q3W).
干预措施: Sintilimab + IBI110 (Combination Product)
结局指标
主要结局
To identify novel immunotherapy IPs to progress into the expansion part (Selection Part)
时间窗: Up to 2 years
Overall response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
To evaluate the antitumor efficacy of immunotherapy in partcipants with unresectable or metastatic melanoma that progressed while on prior treatment(s) that included an anti-PD-1/L1 agent. (Expansion Part)
时间窗: Up to 2 years
ORR by RECIST 1.1
To evaluate the safety, tolerability, and preliminary efficacy of novel immunotherapy IPs in participants with unresectable or metastatic melanoma that progressed while on prior treatment that included an anti-PD-1/L1 agent. (Selection Part)
时间窗: Day 1 to Day 42
Incidence of dose-limiting toxicities (DLTs) \[only applicable for safety run-in portion\]
To evaluate the safety, tolerability, and preliminary efficacy of novel immunotherapy IPs in participants with unresectable or metastatic melanoma that progressed while on prior treatment that included an anti-PD-1/L1 agent. (Selection Part)
时间窗: Up to 28 months
Incidence and severity of Adverse Events (AEs) and laboratory abnormalities
次要结局
- To evaluate the preliminary anti-tumor efficacy by assessing additional endpoints of novel immunotherapy IPs (Selection Part)(Up to 4 years)
- To characterize the pharmacokinetic (PK) profile and immunogenicity (Selection, Expansion Part)(Up to 25 months)
- To evaluate anti-tumor efficacy by assessing additional endpoints by RECIST 1.1 (Expansion Part)(Up to 4 years)
- To further evaluate the safety and tolerability of novel immunotherapy IPs (Expansion Part)(Up to 28 months)
- To evaluate the preliminary anti-tumor efficacy by assessing additional endpoints of novel immunotherapy IPs (Selection Part)(Up to 2 years)
- To evaluate anti-tumor efficacy by assessing additional endpoints by RECIST 1.1 (Expansion Part)(Up to 2 years)