A Phase 1/2 Study Exploring the Safety, Tolerability, and Efficacy of INCAGN01949 in Combination With Immune Therapies in Subjects With Advanced or Metastatic Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 52
- 试验地点
- 15
- 主要终点
- Phase 1: Number of Participants With Treatment-emergent Adverse Events (TEAEs)
研究概览
简要总结
The purpose of this study is to determine the safety, tolerability, and efficacy of INCAGN01949 when given in combination with immune therapies in participants with advanced or metastatic malignancies.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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
- •Locally advanced or metastatic disease; locally advanced disease must not be amenable to resection with curative intent.
- •Phase 1: Subjects with advanced or metastatic solid tumors.
- •Phase 1: Subjects who have disease progression after treatment with available therapies.
- •Phase 2: Subjects with advanced or metastatic gastric cancer, SCCHN, NSCLC, or RCC and are considered refractory to prior PD-1/L1 therapy.
- •Presence of measurable disease based on RECIST v1.
- •Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1.
排除标准
- •Laboratory and medical history parameters not within the Protocol-defined range
- •Receipt of anticancer medications or investigational drugs within protocol-defined intervals before the first administration of study drug.
- •Has not recovered to ≤ Grade 1 from toxic effects of prior therapy.
- •Active autoimmune disease.
- •Known active central nervous system metastases and/or carcinomatous meningitis.
- •Evidence of active, noninfectious pneumonitis or history of interstitial lung disease.
- •Evidence of hepatitis B virus or hepatitis C virus infection or risk of reactivation.
- •Known history of human immunodeficiency virus (HIV); HIV 1/2 antibodies.
研究组 & 干预措施
Phase 1, Safety Expansion: INCAGN01949 + Nivolumab
Run-in with INCAGN01949 (70, 200, or 350 mg) x 2 doses, followed by INCAGN01949 (70, 200, or 350 mg) combined with nivolumab 240 mg in participants with advanced or metastatic select solid tumors
干预措施: Nivolumab (Drug)
Phase 1, Dose Escalation: INCAGN01949 + Nivolumab
INCAGN01949 (70, 200, 350, or 700 milligrams [mg]) combined with nivolumab 240 mg in participants with advanced or metastatic select solid tumors
干预措施: INCAGN01949 (Drug)
Phase 1, Dose Escalation: INCAGN01949 + Nivolumab
INCAGN01949 (70, 200, 350, or 700 milligrams [mg]) combined with nivolumab 240 mg in participants with advanced or metastatic select solid tumors
干预措施: Nivolumab (Drug)
Phase 1, Dose Escalation: INCAGN01949 + Ipilimumab
INCAGN01949 (70, 200, 350, or 700 mg) combined with ipilimumab 1 mg/kilogram (kg) in participants with advanced or metastatic select solid tumors
干预措施: INCAGN01949 (Drug)
Phase 1, Dose Escalation: INCAGN01949 + Ipilimumab
INCAGN01949 (70, 200, 350, or 700 mg) combined with ipilimumab 1 mg/kilogram (kg) in participants with advanced or metastatic select solid tumors
干预措施: Ipilimumab (Drug)
Phase 1, Dose Escalation: INCAGN01949 + Nivolumab + Ipilimumab
INCAGN01949 combined with nivolumab 3 mg/kg and ipilimumab 1 mg/kg in participants with advanced or metastatic select solid tumors
干预措施: INCAGN01949 (Drug)
Phase 1, Dose Escalation: INCAGN01949 + Nivolumab + Ipilimumab
INCAGN01949 combined with nivolumab 3 mg/kg and ipilimumab 1 mg/kg in participants with advanced or metastatic select solid tumors
干预措施: Nivolumab (Drug)
Phase 1, Dose Escalation: INCAGN01949 + Nivolumab + Ipilimumab
INCAGN01949 combined with nivolumab 3 mg/kg and ipilimumab 1 mg/kg in participants with advanced or metastatic select solid tumors
干预措施: Ipilimumab (Drug)
Phase 1, Safety Expansion: INCAGN01949 + Nivolumab
Run-in with INCAGN01949 (70, 200, or 350 mg) x 2 doses, followed by INCAGN01949 (70, 200, or 350 mg) combined with nivolumab 240 mg in participants with advanced or metastatic select solid tumors
干预措施: INCAGN01949 (Drug)
Phase 1, Safety Expansion: INCAGN01949 + Nivolumab + Ipilimumab
Run-in with INCAGN01949 x 2 doses, followed by INCAGN01949 combined with nivolumab 3 mg/kg and ipilimumab 1 mg/kg in participants with advanced or metastatic select solid tumors
干预措施: INCAGN01949 (Drug)
Phase 1, Safety Expansion: INCAGN01949 + Nivolumab + Ipilimumab
Run-in with INCAGN01949 x 2 doses, followed by INCAGN01949 combined with nivolumab 3 mg/kg and ipilimumab 1 mg/kg in participants with advanced or metastatic select solid tumors
干预措施: Nivolumab (Drug)
Phase 1, Safety Expansion: INCAGN01949 + Nivolumab + Ipilimumab
Run-in with INCAGN01949 x 2 doses, followed by INCAGN01949 combined with nivolumab 3 mg/kg and ipilimumab 1 mg/kg in participants with advanced or metastatic select solid tumors
干预措施: Ipilimumab (Drug)
Phase 2, Part A: INCAGN01949 + nivolumab
INCAGN01949 combined with nivolumab in programmed cell death protein 1 (PD-1)/programmed cell death protein ligand 1 (PD-L1) refractory participants with gastric cancer, squamous cell carcinoma of the head and neck (SCCHN), non-small cell lung cancer (NSCLC), or renal cell carcinoma (RCC)
干预措施: INCAGN01949 (Drug)
Phase 2, Part A: INCAGN01949 + nivolumab
INCAGN01949 combined with nivolumab in programmed cell death protein 1 (PD-1)/programmed cell death protein ligand 1 (PD-L1) refractory participants with gastric cancer, squamous cell carcinoma of the head and neck (SCCHN), non-small cell lung cancer (NSCLC), or renal cell carcinoma (RCC)
干预措施: Nivolumab (Drug)
Phase 2, Part B: INCAGN01949; INCAGN01949 + nivolumab; INCAGN01949 + nivolumab + ipilimumab
INCAGN01949 alone, combined with nivolumab, and combined with nivolumab and ipilimumab in PD-1/L1 refractory participants with advanced or metastatic gastric cancer, SCCHN, NSCLC, or RCC
干预措施: INCAGN01949 (Drug)
Phase 2, Part B: INCAGN01949; INCAGN01949 + nivolumab; INCAGN01949 + nivolumab + ipilimumab
INCAGN01949 alone, combined with nivolumab, and combined with nivolumab and ipilimumab in PD-1/L1 refractory participants with advanced or metastatic gastric cancer, SCCHN, NSCLC, or RCC
干预措施: Nivolumab (Drug)
Phase 2, Part B: INCAGN01949; INCAGN01949 + nivolumab; INCAGN01949 + nivolumab + ipilimumab
INCAGN01949 alone, combined with nivolumab, and combined with nivolumab and ipilimumab in PD-1/L1 refractory participants with advanced or metastatic gastric cancer, SCCHN, NSCLC, or RCC
干预措施: Ipilimumab (Drug)
结局指标
主要结局
Phase 1: Number of Participants With Treatment-emergent Adverse Events (TEAEs)
时间窗: up to 17.4 months
An adverse event (AE) was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related, that occurred after a participant provided informed consent. Abnormal laboratory values or test results that occurred after informed consent constituted AEs only if they induced clinical signs or symptoms, were considered clinically meaningful, required therapy (e.g., hematologic abnormality that required transfusion), or required changes in the study drug(s). A TEAE was defined as any adverse event either reported for the first time or the worsening of a pre-existing event after the first dose of study drug.
Phase 1: Number of Participants With a Grade 3 or Higher TEAE
时间窗: up to 17.4 months
An AE was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related, that occurred after a participant provided informed consent. A TEAE was defined as any adverse event either reported for the first time or the worsening of a pre-existing event after the first dose of study drug. The severity of AEs was assessed using Common Terminology Criteria for Adverse Events (CTCAE) v4.03. Grade 1: mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2: moderate; minimal, local, or noninvasive intervention indicated; limiting age-appropriate activities of daily living. Grade 3: severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living. Grade 4: life-threatening consequences; urgent intervention indicated. Grade 5: death due to AE.
Phase 2: Objective Response Rate (ORR)
时间窗: up to 24 months
ORR was defined as the percentage of participants with a confirmed best overall response of complete response (CR) or partial response (PR), per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (v1.1), as determined by investigator assessment of radiographic disease assessments, recorded before and including the first event of progressive disease (PD). CR: disappearance of all target and non-target lesions and no appearance of any new lesions. Any pathological lymph nodes (whether target or non-target) must have a reduction in the short axis to \<10 millimeters (mm). PR: complete disappearance or at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference the baseline sum diameters, no new lesions, and no progression of non-target lesions.
次要结局
- Phase 2: DCR(up to 24 months)
- Phase 1: ORR(up to 15.6 months)
- Phase 2: DOR(up to 24 months)
- Phase 1: Duration of Disease Control(up to 15.4 months)
- Phase 1: Duration of Response (DOR)(up to 11.0 months)
- Phase 1: Disease Control Rate (DCR)(up to 15.6 months)
- Phase 2: Duration of Disease Control(up to 24 months)
- Phase 1: Progression-free Survival (PFS)(up to 15.6 months)
- Phase 2: PFS(up to 24 months)
- Phase 2: Number of Participants With TEAEs(up to 24 months)
- Phase 2: Number of Participants With a Grade 3 or Higher TEAE(up to 24 months)