An Open-label, Multicenter, Phase 1a/1b Study of Aplitibart (IGM-8444) As a Single Agent and in Combination in Participants with Relapsed, Refractory, or Newly Diagnosed Cancers
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 272
- 试验地点
- 56
- 主要终点
- Ph1a: Adverse Events of aplitabart as single agent and with FOLFIRI ± bevacizumab, aplitibart with birinapant, aplitibart with venetoclax, aplitibart with venetoclax and azacitadine, and aplitibart with gemcitabine and docetaxel
研究概览
简要总结
This study is a first-in-human, Phase 1a/1b, multicenter, open-label study to determine the safety, tolerability, and pharmacokinetics of aplitabart as a single agent and in combination in participants with relapsed and/or refractory solid or hematologic cancers, as well as newly diagnosed cancers, and an open-label, randomized study of aplitabart+FOLFIRI+bevacizumab.
详细描述
Participants will be enrolled in Phase 1a, which consists of two stages: a dose-escalation stage and an expansion stage. Aplitabart will be used as a single agent and in combination with numerous other agents where standard therapeutic regimens do not exist, have proven to be ineffective or intolerable, or are considered inappropriate.
Colorectal participants may be enrolled in Phase 1b, an open-label, randomized study of aplitabart+FOLFIRI+ bevacizumab.
Aplitabart will be investigated in numerous tumor types including all-comers solid tumors, colorectal carcinoma (CRC), sarcoma, non-Hodgkin's lymphoma (NHL), acute myeloid leukemia (AML), and chronic lymphocytic leukemia (CLL).
Aplitabart will be administered intravenously (IV).
An alternative dosing schedule may be evaluated.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
盲法说明
Phase 1a is non-randomized; Ph1b is randomized
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
- •Age ≥ 18 years at time of signing ICF
- •ECOG Performance Status of 0 or 1
- •Histologic documentation of incurable, locally advanced or metastatic tumor of the type being evaluated in individual cohorts.
- •Adequate hepatic and renal function and adequate bone marrow reserve function.
- •For combination cohorts, participants must be eligible to receive the chemotherapy or targeted agent.
- •Ph1a only: No more than three prior therapeutic regimens.
- •Ph1b only: Must be FOLFIRI naïve participants and must have received only 1 prior therapeutic regimen administered for the treatment of cancer in the advanced/metastatic setting - OR - FOLFIRI naïve participants that only received adjuvant therapy who progressed within six months after completing adjuvant therapy, and are confirmed to have locally advanced/metastatic disease
排除标准
- •Inability to comply with study and follow-up procedures.
- •Prior DR5 agonist therapy.
- •Concomitant use of agents well-known to cause liver toxicity.
- •Concomitant use of anti-cancer agents
- •Palliative radiation to bone metastases within 2 weeks prior to Day
- •Major surgical procedure within 4 weeks prior to Day
- •Untreated or active central nervous system (CNS) metastases (progressing or requiring anticonvulsants or corticosteroids for symptomatic control). Participants with a history of treated CNS metastases are eligible.
- •Prior use of any chemotherapeutic agent or small molecule inhibitors (SMI) within 2 weeks or 5 half-lives, prior to the first dose of study treatment
- •Treatment with a monoclonal antibody, or any other anticancer agent (including biologic, experimental, or hormonal therapy) investigational or otherwise, that is not chemotherapy or a SMI, within 4 weeks or five half-lives prior to first dose of study treatment.
- •Ph1b: Participants who have previously received FOLFIRI treatment in the adjuvant, advanced, or metastatic disease setting
研究组 & 干预措施
Ph1a: Aplitabart Single Agent Alternate Dosing Escalation
Aplitabart will be administered intravenously as a single agent on an alternate dosing schedule.
干预措施: Aplitabart (IGM-8444) (Drug)
Ph1a: Aplitabart + FOLFIRI ± bevacizumab Escalation and Expansion
Aplitabart will be administered intravenously in combination with FOLFIRI± bevacizumab.
干预措施: Aplitabart (IGM-8444) (Drug)
Ph1a: Aplitabart + FOLFIRI ± bevacizumab Escalation and Expansion
Aplitabart will be administered intravenously in combination with FOLFIRI± bevacizumab.
干预措施: FOLFIRI (Drug)
Ph1a: Aplitabart + FOLFIRI ± bevacizumab Escalation and Expansion
Aplitabart will be administered intravenously in combination with FOLFIRI± bevacizumab.
干预措施: Bevacizumab (and approved biosimilars) (Drug)
Ph1a: Aplitabart + Birinapant Escalation and Expansion
Aplitabart will be administered intravenously in combination with Birinapant which will also be administered intravenously.
干预措施: Aplitabart (IGM-8444) (Drug)
Ph1a: Aplitabart + Birinapant Escalation and Expansion
Aplitabart will be administered intravenously in combination with Birinapant which will also be administered intravenously.
干预措施: Birinapant (Drug)
Ph1a: Aplitabart + Venetoclax Escalation and Expansion
Aplitabart will be administered intravenously in combination with Venetoclax.
干预措施: Aplitabart (IGM-8444) (Drug)
Ph1a: Aplitabart + Venetoclax Escalation and Expansion
Aplitabart will be administered intravenously in combination with Venetoclax.
干预措施: Venetoclax (Drug)
Ph1a: Aplitabart + Docetaxel + Gemcitabine Escalation and Expansion
Aplitabart will be administered intravenously in combination with Docetaxel and Gemcitabine.
干预措施: Aplitabart (IGM-8444) (Drug)
Ph1a: Aplitabart + Docetaxel + Gemcitabine Escalation and Expansion
Aplitabart will be administered intravenously in combination with Docetaxel and Gemcitabine.
干预措施: Gemcitabine (Drug)
Ph1a: Aplitabart + Docetaxel + Gemcitabine Escalation and Expansion
Aplitabart will be administered intravenously in combination with Docetaxel and Gemcitabine.
干预措施: Docetaxel (Drug)
Ph1a: Aplitabart + Venetoclax + Azacitidine Escalation and Expansion
Aplitabart will be administered intravenously in combination with Venetoclax and Azacitidine.
干预措施: Aplitabart (IGM-8444) (Drug)
Ph1a: Aplitabart + Venetoclax + Azacitidine Escalation and Expansion
Aplitabart will be administered intravenously in combination with Venetoclax and Azacitidine.
干预措施: Venetoclax (Drug)
Ph1a: Aplitabart + Venetoclax + Azacitidine Escalation and Expansion
Aplitabart will be administered intravenously in combination with Venetoclax and Azacitidine.
干预措施: Azacitidine (Drug)
Ph1b: Aplitabart + FOLFIRI + Bevacizumab
Aplitabart will be administered intravenously in combination with FOLFIRI + bevacizumab
干预措施: Aplitabart (IGM-8444) (Drug)
Ph1b: Aplitabart + FOLFIRI + Bevacizumab
Aplitabart will be administered intravenously in combination with FOLFIRI + bevacizumab
干预措施: FOLFIRI (Drug)
Ph1b: Aplitabart + FOLFIRI + Bevacizumab
Aplitabart will be administered intravenously in combination with FOLFIRI + bevacizumab
干预措施: Bevacizumab (and approved biosimilars) (Drug)
Ph1b: FOLFIRI + Bevacizumab
Standard of Care FOLFIRI + bevacizumab will be administered intravenously
干预措施: FOLFIRI (Drug)
Ph1b: FOLFIRI + Bevacizumab
Standard of Care FOLFIRI + bevacizumab will be administered intravenously
干预措施: Bevacizumab (and approved biosimilars) (Drug)
结局指标
主要结局
Ph1a: Adverse Events of aplitabart as single agent and with FOLFIRI ± bevacizumab, aplitibart with birinapant, aplitibart with venetoclax, aplitibart with venetoclax and azacitadine, and aplitibart with gemcitabine and docetaxel
时间窗: From Cycle 1 Day 1 through 28 days after the final dose of study drug
Incidence of treatment-related AEs graded according to the NCI Common Technology Criteria for Adverse Events (CTCAE) v5.0
Ph1b: Progression-Free Survival (PFS)
时间窗: Study duration of approximately 36 months
PFS is defined as the time from randomization to the first documented disease progression per RECIST 1.1 by investigator or death, whichever occurs first.
Ph1a: To identify the recommended expansion dose for aplitabart as single agent, with FOLFIRI ± bevacizumab, aplitibart with birinapant, aplitibart with venetoclax, aplitibart with venetoclax and azacitadine, and aplitibart with gemcitabine and docetaxel
时间窗: 4 weeks
Relationship between aplitabart dose and safety, PK, activity, and endpoints.
次要结局
- Ph1b: Adverse events of aplitabart + FOLFIRI + bevacizumab(From Cycle 1 Day 1 through 28 days after the final dose of study drug)
- Ph1a and Ph1b: Clearance (CL) of aplitabart(At pre-defined intervals from Cycle 1 Day 1 through end of treatment at approximately 6 months)
- Ph1a and Ph1b: Area Under the Curve (AUC) of aplitabart(At pre-defined intervals from Cycle 1 Day 1 through end of treatment at approximately 6 months)
- Ph1a and Ph1b: Volume of distribution (V) of aplitabart(At pre-defined intervals from Cycle 1 Day 1 through end of treatment at approximately 6 months)
- Ph1a and Ph1b: Maximum Concentration (c-max) of aplitabart(At pre-defined intervals from Cycle 1 Day 1 through end of treatment at approximately 6 months)
- Ph1a and Ph1b: Immunogenicity(through end of treatment at approximately 6 months)
- Ph1a and Ph1b: Objective Response Rate (ORR)(Study duration of approximately 36 months)
- Ph1a and Ph1b: Duration of Response (DoR)(Study duration of approximately 36 months)
- Ph1a: Progression-Free Survival (PFS)(Study duration of approximately 36 months)
- Ph1a and Ph1b: Overall Survival (OS)(Study duration of approximately 36 months)