An Open-Label, Dose-Escalation Phase 1/1b Study of the Anti-gp75 Monoclonal Antibody IMC-20D7S In Patients With Malignant Melanoma Who Have Progressed After or During at Least One Treatment With Standard Cytotoxic Treatment or/and Immunotherapy Therapy or For Whom Standard Therapy is Not Indicated
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 27
- 试验地点
- 2
- 主要终点
- Maximum Tolerated Dose (MTD) of IMC-20D7S
研究概览
简要总结
A dose-escalation study designed to determine the safety, maximum tolerated dose (MTD), anti-melanoma activity, antibody blood levels and progression-free survival (PFS) in participants with malignant melanoma receiving IMC-20D7S either every 2 weeks or every 3 weeks.
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
- •Participant has histologically or cytologically confirmed cutaneous, mucosal, or uveal malignant melanoma which has progressed after or during at least 1 treatment with standard cytotoxic treatment or/and immunotherapy [for example (e.g.), treatment with cytokines, monoclonal antibodies, and vaccines] and is not regarded to be a candidate for a potentially curative, higher priority treatment for melanoma
- •Participant is ≥18 years of age
- •Participant has either measurable disease as defined by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) or evaluable disease
- •At least 21 days must have elapsed from major surgery, prior chemotherapy, prior treatment with an investigational agent or device, or prior radiation therapy. Relative to participant's treatment with non-approved biological products (eg, monoclonal antibodies), a minimum of 2 half-lives must have passed for eligibility to be considered
- •Participant has resolution of all clinically significant toxic effects of prior cancer therapy to Grade ≤1 according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.02 (NCI-CTCAE v4.02)
- •Participant has adequate hematological function, hepatic function, and renal function
排除标准
- •Participant has undergone major surgery [e.g., laparotomy, thoracotomy, removal of organ(s)] within 21 days prior to study entry
- •Participant has elective or planned surgery to be conducted during the trial
- •Participant has documented and/or symptomatic brain or leptomeningeal metastases
- •Participant is receiving systemic steroids or other immunosuppressive medications. (Intermittent use of steroid-containing medications e.g., for asthma exacerbation or for skin lesions is permitted)
- •Participant has an uncontrolled undercurrent illness
- •Participant has a concurrent active malignancy other than adequately treated nonmelanomatous skin cancer or other noninvasive carcinoma or in situ neoplasm
- •Participant has a known allergy to any of the treatment components (monoclonal antibodies or other therapeutic proteins such as fresh frozen plasma, human serum albumin, cytokines, or interleukins). In the event that there is suspicion the participant may have allergies, the participant should be excluded
- •Participant is pregnant or lactating
- •Participant has known human immunodeficiency virus (HIV) or acquired immune deficiency syndrome (AIDS) infection
研究组 & 干预措施
IMC-20D7S (1A-4A Cohorts)
Escalating doses up to 30 milligrams per kilogram (mg/kg) administered intravenously (i.v.) every 2 weeks; includes Cohorts 1A, 2A, 3A, and 4A.
干预措施: IMC-20D7S (Cohort 1A) (Biological)
IMC-20D7S (1A-4A Cohorts)
Escalating doses up to 30 milligrams per kilogram (mg/kg) administered intravenously (i.v.) every 2 weeks; includes Cohorts 1A, 2A, 3A, and 4A.
干预措施: IMC-20D7S (Cohort 2A) (Biological)
IMC-20D7S (1A-4A Cohorts)
Escalating doses up to 30 milligrams per kilogram (mg/kg) administered intravenously (i.v.) every 2 weeks; includes Cohorts 1A, 2A, 3A, and 4A.
干预措施: IMC-20D7S (Cohort 3A) (Biological)
IMC-20D7S (1A-4A Cohorts)
Escalating doses up to 30 milligrams per kilogram (mg/kg) administered intravenously (i.v.) every 2 weeks; includes Cohorts 1A, 2A, 3A, and 4A.
干预措施: IMC-20D7S (Cohort 4A) (Biological)
IMC-20D7S (1B-3B Cohorts)
Escalating doses up to 30 mg/kg administered i.v. every 3 weeks; includes Cohorts 1B, 2B, and 3B.
干预措施: IMC-20D7S (Cohort 1B) (Biological)
IMC-20D7S (1B-3B Cohorts)
Escalating doses up to 30 mg/kg administered i.v. every 3 weeks; includes Cohorts 1B, 2B, and 3B.
干预措施: IMC-20D7S (Cohort 2B) (Biological)
IMC-20D7S (1B-3B Cohorts)
Escalating doses up to 30 mg/kg administered i.v. every 3 weeks; includes Cohorts 1B, 2B, and 3B.
干预措施: IMC-20D7S (Cohort 3B) (Biological)
结局指标
主要结局
Maximum Tolerated Dose (MTD) of IMC-20D7S
时间窗: Baseline to toxicity [up to end of Cycle 1 (4 or 6-week cycles)]
The MTD was defined as the dose preceding the dose level at which 2 participants experienced a dose-limiting toxicity (DLT) during treatment Cycle 1. A DLT was defined as any Grade 3 or above toxicity that emerged during study treatment and was clearly not attributable to malignant melanoma or co-medication and was possibly, probably, or definitely related to IMC-20D7S in the judgment of the investigator. No DLT was observed in the study; a provisional MTD was established.
Number of Participants With Serious Adverse Events (SAEs), Other Non-Serious Adverse Events (AEs), or Death
时间窗: Baseline through 30 days post last dose (up to 31 weeks)
A summary of SAEs and other non-serious AEs, regardless of causality, is located in the Reported Adverse Event module.
次要结局
- IMC-20D7S PK: Half-life (t½)(Cycles 1 and 3: Prior to, immediately after, and 0.5, 1, 2, 4, 8, 24, 48 (Cycle 3 only), 96, 168, 240, and 336 h post first infusion. Cycles 2 and 4: Prior to and 1 h post first infusion.)
- Recommend Doses for Phase 2/3 Studies Based on MTD(Baseline to toxicity [up to end of Cycle 1 (4-or 6-week cycles)])
- IMC-20D7S Pharmacokinetics (PK): Maximum Concentration (Cmax)(Cycles 1 and 3: Prior to, immediately after, and 0.5, 1, 2, 4, 8, 24, 48 (Cycle 3 only), 96, 168, 240, and 336 hours (h) post first infusion. Cycles 2 and 4: Prior to and 1 h post first infusion.)
- IMC-20D7S PK: Minimal Concentration (Cmin)(Cycles 1 and 3: Prior to, immediately after, and 0.5, 1, 2, 4, 8, 24, 48 (Cycle 3 only), 96, 168, 240, and 336 h post first infusion. Cycles 2 and 4: Prior to and 1 h post first infusion.)
- IMC-20D7S PK: Clearance (Cl)(Cycles 1 and 3: Prior to, immediately after, and 0.5, 1, 2, 4, 8, 24, 48 (Cycle 3 only), 96, 168, 240, and 336 h post first infusion. Cycles 2 and 4: Prior to and 1 h post first infusion.)
- Progression-Free Survival (PFS)(First dose to disease progression or death (up to 27 weeks))
- Number of Participants Who Develop Antibodies Against IMC-20D7S (Immunogenicity)(Prior to the first and second infusion in each cycle up to Cycle 7 (4- and 6-week cycles))
- IMC-20D7S PK: Area Under the Concentration Versus Time Curve (AUC)(Cycles 1 and 3: Prior to, immediately after, and 0.5, 1, 2, 4, 8, 24, 48 (Cycle 3 only), 96, 168, 240, and 336 h post first infusion. Cycles 2 and 4: Prior to and 1 h post first infusion.)
- IMC-20D7S PK: Volume of Distribution (Vd) at Steady State(Cycles 1 and 3: Prior to, immediately after, and 0.5, 1, 2, 4, 8, 24, 48 (Cycle 3 only), 96, 168, 240, and 336 h post first infusion. Cycles 2 and 4: Prior to and 1 h post first infusion.)