IMPORT-201: A Phase 1 First-in-Human Dose Finding/Randomized Phase 2 Study of IMM60 and Pembrolizumab for Advanced Melanoma and Metastatic NSCLC
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 1
- 试验地点
- 14
- 主要终点
- Phase 1 Co-Primary Objective - Identify Maximum Tolerated Dose (MTD)
研究概览
简要总结
The goal of this clinical trial is to learn about IMM60 with or without pembrolizumab in participants with advanced melanoma or non-small cell lung cancer. There are two phases:
- Phase 1: This phase is designed to learn about the safety of IMM60 with or without pembrolizumab and to find a safe dose to test in Phase 2.
- Phase 2: This phase is designed to learn whether IMM60 + pembrolizumab improves progression-free survival at 12 months compared to pembrolizumab alone in participants with non-small cell lung cancer.
详细描述
This exploratory phase 1/phase 2 study is designed to establish a recommended phase 2 dose of IMM60 and provide preliminary estimates of safety and efficacy of IMM60 alone and in combination with pembrolizumab in participants with NSCLC and melanoma. In phase 1, initial safety will be assessed in a multiple dose escalation cohort for IMM60 alone, then for the IMM60 + pembrolizumab combination. Phase 2 of the study will recruit PD-1 pretreated melanoma participants and randomize PD-L1 > 50% total NSCLC participants 2:1 to IMM60 + pembrolizumab vs pembrolizumab alone. There is an additional cohort of PD-L1 < 1% NSCLC participants.
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
- •Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score 0 to 1
- •Adequate organ function
- •At least 1 lesion, not previously irradiated, that can be accurately measured on CT or MRI as defined by RECIST 1.1 criteria
- •NSCLC cohorts: Histologically confirmed diagnosis of stage IV NSCLC
- •NSCLC cohorts: Patients with adenocarcinoma histology must not have sensitizing epidermal growth factor receptor (EGFR) or ROS proto-oncogene 1 (ROS1) mutations or anaplastic lymphoma kinase (ALK) translocations
- •NSCLC cohorts: Participants in NSCLC arms must have a PD-L1 assessment (PD-L1 immuno-histochemistry (IHC) 22C3 pharmDx)
- •Melanoma cohorts: Unresectable stage III or IV, histologically confirmed diagnosis of cutaneous or unknown primary melanoma
- •Melanoma cohorts: B-type Raf proto-oncogene (BRAF) mutation status available
- •Male participants: Participant must agree to use contraception and refrain from sperm donation during the treatment period and for at least 120 days after the last dose of study intervention
- •Female participants: Participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
- •Not a woman of childbearing potential (WOCBP)
- •A WOCBP who agrees to follow contraceptive guidance during the treatment period and for at least 6 months after the last dose of study intervention
排除标准
- •Has the following cardiac conditions:
- •Corrected QT interval (QTc) > 450 ms
- •Uncontrolled hypertension with blood pressure (BP) > 160/100 despite treatment
- •Class II or greater heart failure as defined by the New York Heart Association
- •Myocardial infarction within 6 months or angina requiring nitrate therapy more than once a week
- •Another active malignancy within the past 2 years (Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder, or carcinoma in situ [e.g., breast carcinoma, cervical cancer in situ] that have undergone potentially curative therapy are not excluded. Also, prostate, breast, and neuroendocrine tumors that are stable on hormonal treatment for a period of 1 year or more without the need to adjust dose are not excluded.)
- •Has had an allogeneic tissue/solid organ transplant
- •Known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable.
- •History of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
- •Participants with an active autoimmune disease or a documented history of autoimmune disease or syndrome that requires systemic steroids (in dosing exceeding 10 mg daily of prednisone equivalent) or immunosuppressive agents.
- •Participants who are known to be serologically positive for Hepatitis B, Hepatitis C, or human immunodeficiency virus.
研究组 & 干预措施
Phase 1 IMM60 dose escalation safety arm
3 dose levels of IMM60 will be assessed (1, 3, 9 and 36 mg/m^2 administered IV every 3 weeks for up to 6 cycles)
干预措施: IMM60 (Drug)
Phase 1 IMM60 + pembrolizumab combination safety arm
Pembrolizumab 200 mg IV every 3 weeks for up to 35 cycles will be administered in combination with IMM60 IV every 3 weeks for up to 6 cycles. The IMM60 dose will be determined based on the results of the IMM60 dose escalation safety cohort.
干预措施: IMM60 (Drug)
Phase 1 IMM60 + pembrolizumab combination safety arm
Pembrolizumab 200 mg IV every 3 weeks for up to 35 cycles will be administered in combination with IMM60 IV every 3 weeks for up to 6 cycles. The IMM60 dose will be determined based on the results of the IMM60 dose escalation safety cohort.
干预措施: Pembrolizumab (Drug)
Phase 2 PD-L1 ≥50% NSCLC Cohort 1 (Randomized, IMM60 + pembrolizumab)
Pembrolizumab 200 mg IV every 3 weeks for up to 35 cycles will be administered in combination with IMM60 IV every 3 weeks for up to 6 cycles. The IMM60 dose will be determined based on the results of the Phase 1 dose escalation safety cohorts.
干预措施: IMM60 (Drug)
Phase 2 PD-L1 ≥50% NSCLC Cohort 1 (Randomized, IMM60 + pembrolizumab)
Pembrolizumab 200 mg IV every 3 weeks for up to 35 cycles will be administered in combination with IMM60 IV every 3 weeks for up to 6 cycles. The IMM60 dose will be determined based on the results of the Phase 1 dose escalation safety cohorts.
干预措施: Pembrolizumab (Drug)
Phase 2 PD-L1 ≥50% NSCLC Cohort 1 (Randomized, pembrolizumab monotherapy)
Pembrolizumab 200 mg IV every 3 weeks for up to 35 cycles.
干预措施: Pembrolizumab (Drug)
Phase 2 PD-L1 <1% NSCLC Cohort 2
Participants will be treated with one cycle of IMM60 with a tumor biopsy before and after, to determine any changes in PD-L1 expression. After this one cycle, the participants will receive the combination of IMM60 IV for up to 6 total cycles + pembrolizumab 200 mg every 3 weeks administered IV. The IMM60 dose will be determined based on the results of the Phase 1 dose escalation cohorts.
干预措施: IMM60 (Drug)
Phase 2 PD-L1 <1% NSCLC Cohort 2
Participants will be treated with one cycle of IMM60 with a tumor biopsy before and after, to determine any changes in PD-L1 expression. After this one cycle, the participants will receive the combination of IMM60 IV for up to 6 total cycles + pembrolizumab 200 mg every 3 weeks administered IV. The IMM60 dose will be determined based on the results of the Phase 1 dose escalation cohorts.
干预措施: Pembrolizumab (Drug)
Melanoma Cohort
IMM60 IV every 3 weeks for up to 6 cycles. The IMM60 dose will be determined based on the results of the Phase 1 dose escalation cohorts.
干预措施: IMM60 (Drug)
结局指标
主要结局
Phase 1 Co-Primary Objective - Identify Maximum Tolerated Dose (MTD)
时间窗: Assessed at the end of Cycle 1 for each patient (each Cycle is 28 days)
To confirm the maximum tolerated dose (MTD) of IMM60 alone and in combination with pembrolizumab, defined as the highest dose level at which \<2 out of 6 participants experience a dose-limiting toxicity
Phase 1 Co-Primary Objective - Safety
时间窗: Through Phase 1 completion, an average of 1 year
To characterize the safety of IMM60 alone and in combination with pembrolizumab, as assessed by the frequency of Grade 3 or higher treatment-related adverse events
Phase 2 Primary Objective - Progression-free Survival
时间窗: 12 months after last participant enrolled
To compare the progression-free survival (PFS) rate at 12 months in the randomized arms comparing pembrolizumab alone versus IMM60 + pembrolizumab in patients with advanced PD-L1 ≥50% NSCLC
次要结局
- Pharmacokinetics of IMM60 - Cmax (IMM60 arms only)(During Cycles 1 and 3 (each Cycle is 28 days))
- To characterize the safety of IMM60 alone or in combination with pembrolizumab(Through study completion, an average of 3 years)
- To determine if IMM60 can restore sensitivity in PD-1 inhibitor-resistant melanoma (phase 2)(12 months after last participant enrolled)
- Pharmacokinetics of IMM60 - AUC (IMM60 arms only)(During Cycles 1 and 3 (each Cycle is 28 days))
- Objective Response Rate (ORR)(12 months after last participant enrolled)
- To determine if IMM60 can sensitize patients with programmed death-ligand 1 (PD-L1) <1% NSCLC to PD-1 inhibition(12 months after last participant enrolled)
- To assess the ability of IMM60 to convert PD-L1 negative patients to PD-L1 positive(12 months after last participant enrolled)