A Phase 1/2 First-in-human Study of the Safety and Efficacy of IMC-C103C as Single Agent and in Combination With Atezolizumab in HLA-A*0201-positive Patients With Advanced MAGE-A4-positive Cancer
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 入组人数
- 75
- 试验地点
- 18
- 主要终点
- Phase 1: Incidence of dose-limiting toxicities (DLT)
研究概览
简要总结
IMC-C103C is an immune mobilizing monoclonal T cell receptor against cancer (ImmTAC ®) designed for the treatment of cancers positive for the tumor-associated antigen MAGE-A4. This is a first-in-human trial designed to evaluate the safety and efficacy of IMC-C103C in adult patients who have the appropriate HLA-A2 tissue marker and whose cancer is positive for MAGE-A4.
详细描述
The IMC-C103C-101 Phase 1/2 study will be evaluated in patients with metastatic/unresectable tumors which include select Advanced Solid Tumors and will be conducted in two phases.
- To identify the maximum tolerated dose (MTD) and/or expansion dose of IMC-C103C as a single agent administered intravenously (IV) and subcutaneously (SC) once weekly (Q1W) and administered Q1W in combination with once every 3 weeks (Q3W) atezolizumab.
- To assess the preliminary anti-tumor activity of IMC-C103C in one or more selected indications, as a single agent administered Q1W.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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
- •HLA-A*02:01 positive
- •MAGE-A4 positive tumor
- •Eastern Cooperative Oncology Group (ECOG) performance status (PS) [ECOG PS] 0 or 1
- •Selected advanced solid tumors
- •Relapsed from, refractory to, or intolerant of standard therapy
- •Measurable disease per RECIST v1.1 (expansion)
- •If applicable, must agree to use highly effective contraception
排除标准
- •Symptomatic or untreated central nervous system metastasis
- •Inadequate washout from prior anticancer therapy
- •Significant ongoing toxicity from prior anticancer treatment
- •Impaired baseline organ function as evaluated by out-of-range laboratory values
- •Clinically significant cardiac disease
- •Active infection requiring systemic antibiotic therapy
- •Known history of human immunodeficiency virus (HIV)
- •Active hepatitis B virus (HBV) or hepatitis C virus (HCV)
- •Ongoing treatment with systemic steroids or other immunosuppressive therapies
- •Significant secondary malignancy
- •Pregnancy or lactation
研究组 & 干预措施
IMC-C103C - Monotherapy IV dose escalation
n= approximately 50 patients to establish the MTD/expansion dose
干预措施: IMC-C103C (Drug)
IMC-C103C and atezolizumab dose escalation
n=approximately 12 patients to establish the MTD/expansion dose
干预措施: IMC-C103C (Drug)
IMC-C103C and atezolizumab dose escalation
n=approximately 12 patients to establish the MTD/expansion dose
干预措施: Atezolizumab (Drug)
IMC-C103C - expansion
Patients will be enrolled n=9-24 per expansion cohort (up to 4 total): metastatic/unresectable tumors of interest patients treated at the expansion dose of IMC-C103C to assess preliminary anti-tumor efficacy
干预措施: IMC-C103C (Drug)
IMC-C103C monotherapy SC dose escalation
Patients will be enrolled n=9-12 to establish the MTD/expansion dose
干预措施: IMC-C103C (Drug)
结局指标
主要结局
Phase 1: Incidence of dose-limiting toxicities (DLT)
时间窗: From first dose to DLT period (28 days)
Phase 1: incidence and severity of adverse events (AE)
时间窗: from first dose to 30 days after the last dose
Phase 1: changes in laboratory parameters
时间窗: from first dose to 30 days after the last dose
Abnormalities will be classified according to NCI CTCAE v5.0
Phase 1: changes in vital signs
时间窗: from first dose to 30 days after the last dose
Abnormalities will be classified according to NCI CTCAE v5.0
Phase 1: changes in electrocardiogram parameters
时间窗: from first dose to 30 days after the last dose
QT intervals corrected for heart rate using Fridericia's (cube root) correction (QTcF) interval absolute values and changes from baseline will be summarized
Phase 1: dose interruptions, reductions, and discontinuations
时间窗: from first dose through last dose (anticipated for up to 12-24 months)
Phase 2: Best overall response (BOR)
时间窗: from first dose to approximately 2 years
次要结局
- Progression-free survival(from first dose to approximately 2 years)
- Pharmacokinetics The elimination half-life (t1/2)(from first dose to within approx, 2 weeks of last dose/4 weeks (IMC-C103C AUC will be assessed weekly for 4 weeks))
- Immunogenicity the incidence of anti-drug antibody formation(from first dose to 14 days after the last dose)
- Phase 2: incidence and severity of adverse events (AE)(from first dose to 30 days after the last dose)
- Phase 2: dose interruptions, reductions, and discontinuations(from first dose through last dose (anticipated for up to 12-24 months))
- Changes in lymphocyte counts over time(from first dose to approx 4 weeks)
- Phase 2: changes in laboratory parameters(from first dose to 30 days after the last dose)
- Phase 2: changes in vital signs(from first dose to 30 days after the last dose)
- Phase 2: changes in electrocardiogram parameters(from first dose to 30 days after the last dose)
- Phase 1: Best overall response(from first dose to approximately 2 years)
- Pharmacokinetics Area under the plasma concentration-time curve (AUC)(from first dose to within approx, 2 weeks of last dose/4 weeks (IMC-C103C AUC will be assessed weekly for 4 weeks))
- Duration of response(from first dose to approximately 2 years)
- Overall survival(from first dose to approximately 2 years)
- Pharmacokinetics The maximum observed plasma drug concentration after single dose administration (Cmax)(from first dose to within approx, 2 weeks of last dose/4 weeks (IMC-C103C AUC will be assessed weekly for 4 weeks))
- Pharmacokinetics The time to reach maximum plasma concentration (Tmax)(from first dose to within approx, 2 weeks of last dose/4 weeks (IMC-C103C AUC will be assessed weekly for 4 weeks))
- Changes in serum cytokines over time(from first dose to approx.. 4wks)
- GCIG CA-125 response (ovarian carcinoma)(from first dose to approx.. 30 days after the last dose)