Phase 1/2 Study of IMC-F106C in Advance PRAME-Positive Cancers
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 410
- 试验地点
- 127
- 主要终点
- Phase 1: Incidence of dose-limiting toxicity (DLT)s
研究概览
简要总结
Brenetafusp (IMC-F106C) is an immune-mobilizing monoclonal T cell receptor against cancer (ImmTAC ®) designed for the treatment of cancers positive for the tumor-associated antigen PRAME. This is a first-in-human trial designed to evaluate the safety and efficacy of brenetafusp in adult participants who have the appropriate HLA-A2 tissue marker and whose cancer is positive for PRAME.
详细描述
The IMC-F106C-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.
- Phase 1: To identify the Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 dose (RP2D) of brenetafusp as a single agent and administered in combination with chemotherapies, targeted therapies, and monoclonal antibodies.
- Phase 2: To assess the efficacy of brenetafusp in selected advanced solid tumors.
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
- •ECOG PS 0 or 1
- •HLA-A*02:01 positive
- •PRAME positive tumor
- •Relapsed from, refractory to, or intolerant of standard therapies; or, in combination with standard therapies
- •If applicable, must agree to use highly effective contraception
排除标准
- •Symptomatic or untreated central nervous system metastasis
- •Recent bowel obstruction
- •Ongoing ascites or effusion requiring recent drainages
- •Significant immune-mediated adverse event with prior immunotherapy (Participants in checkpoint inhibitor combination treatment)
- •Inadequate washout from prior anticancer therapy
- •Significant ongoing toxicity from prior anticancer treatment
- •Out-of-range laboratory values
- •Clinically significant lung, heart, or autoimmune disease
- •Ongoing requirement for immunosuppressive treatment
- •Prior solid organ or bone marrow transplant
- •Active hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV) infection
- •Significant secondary malignancy
- •Hypersensitivity to study drug or excipients
- •Antibiotics, vaccines or surgery within 2-4 weeks prior to the first dose of study intervention
- •Pregnant or lactating participants
- •Any other contraindication for applicable combination partner based on local prescribing information
研究组 & 干预措施
Brenetafusp Monotherapy
Participants receive brenetafusp.
干预措施: Brenetafusp (Drug)
Brenetafusp and Anti-PD(L)1 Agent
Participants receive brenetafusp and pembrolizumab.
干预措施: Brenetafusp and pembrolizumab (Drug)
Brenetafusp and Chemotherapy
Participants receive brenetafusp and chemotherapy. Choice of chemotherapy is dependent on cohort.
干预措施: Brenetafusp and chemotherapy (Drug)
Brenetafusp and Targeted Therapy
Participants receive brenetafusp and a selected targeted therapy. Receipt of kinase inhibitor is dependent on histology.
干预措施: Brenetafusp and tebentafusp (Drug)
Brenetafusp and Targeted Therapy
Participants receive brenetafusp and a selected targeted therapy. Receipt of kinase inhibitor is dependent on histology.
干预措施: Brenetafusp and bevacizumab (Drug)
Brenetafusp and Targeted Therapy
Participants receive brenetafusp and a selected targeted therapy. Receipt of kinase inhibitor is dependent on histology.
干预措施: Brenetafusp and kinase inhibitors (Drug)
Brenetafusp and Multimodal Therapy
Participants receive brenetafusp, biologics (eg, pembrolizumab, bevacizumab) IV infusions and chemotherapy IV infusions based on histology.
干预措施: Brenetafusp and monoclonal antibodies and chemotherapy (Drug)
结局指标
主要结局
Phase 1: Incidence of dose-limiting toxicity (DLT)s
时间窗: Up to ~28 days after each dose
Phase 1: Incidence of adverse events (AE) and serious adverse events (SAE)
时间窗: Up to 30 days after the last dose of study therapy
Phase 1: Number of participants with dose interruptions, dose reductions, or dose discontinuations
时间窗: Up to ~12 months
Phase 1: Number of participants with abnormal laboratory test results (hematology)
时间窗: Up to 30 days after the last dose of study therapy
Phase 1: Number of participants with abnormal laboratory test results (chemistry)
时间窗: Up to 30 days after the last dose of study therapy
Phase 1: Number of participants with abnormal laboratory test results (coagulation)
时间窗: Up to 30 days after the last dose of study therapy
Phase 1: Number of participants with abnormal urinalysis
时间窗: Up to 30 days after the last dose of study therapy
Phase 1: Number of participants with abnormal vital signs
时间窗: Up to 30 days after the last dose of study therapy
Phase 1: Mean change from baseline in QTcF interval
时间窗: Up to 30 days after the last dose of study therapy
Phase 2: Best overall response (BOR)
时间窗: Up to ~2 years
次要结局
- Phase I: Best Overall Response (BOR)(Up to ~2 years)
- Progression-free survival (PFS)(Up to ~2 years)
- Duration of response (DOR)(Up to ~2 years)
- Overall survival(Up to ~2 years)
- Area under the plasma concentration-time curve (AUC) of brenetafusp(At designated time points up to ~3 weeks)
- Maximum plasma drug concentration (Cmax) of brenetafusp(At designated time points up to ~3 weeks)
- Time to reach maximum plasma concentration (Tmax) of brenetafusp(At designated time points up to ~3 weeks)
- Plasma elimination half-life (t½) of brenetafusp(At designated time points up to ~3 weeks)
- Incidence of anti-brenetafusp antibody formation(Up to ~ 2 years)
- Changes in lymphocyte counts over time(Up to ~3 weeks)
- Changes in serum cytokines over time(Up to ~3 weeks)
- Local tumor response based on Gynecological Cancer Intergroup (GCIG) Cancer Antigen 25 (CA-125) response criteria(Up to ~2 years)