A First-in-Human, Open-Label, Phase 1/2 Dose-Escalation With Enrichment and Dose-Expansion Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Antitumor Activity of GIM-122 as a Single Agent in Adult Subjects With Advanced Solid Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 111
- 试验地点
- 20
- 主要终点
- Recommended Phase 2 Dose [RP2D] of GIM-122
研究概览
简要总结
GIM-122 is a first-in-class, humanized immunoglobulin G1 kappa dual functioning monoclonal antibody (DFA). This phase 1 / 2 study plans to evaluate the safety, tolerability, pharmacokinetics and clinical efficacy of intravenous (IV) administration of GIM-122 in adults with advanced malignancies.
详细描述
This is a Phase 1/2, open label, first-in-human (FIH), multicenter, dose escalation study with enrichments and dose expansion cohorts at RP2D, designed to evaluate the safety, tolerability, PK, pharmacodynamics, and preliminary antitumor activity of GIM-122 administered as a single agent in adults with advanced solid malignancies. This study will be conducted in 2 parts: Phase 1 or Part A (dose escalation and enrichment) and Phase 2 or Part B (dose optimization and cohort expansion).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •Written informed consent
- •ECOG performance status 0-
- •Laboratory assessment 28 days prior to enrollment for assessment of acceptable cardiac, renal and hepatic functions
- •Recommended Double methods of contraception 90-days post treatment Cancer Specific
- •Histologically or cytologically confirmed locally advanced/unresectable or metastatic solid tumor
- •Received FDA approved treatment of PD-1 inhibitor or PD-L1 inhibitor for advance malignant tumors and have progressed/relapsed, are refractory, or intolerant
- •Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1
- •Had prior therapy with PD-1/PD-L1 inhibitors. Other checkpoint inhibitors (ie, CTLA4, LAG3) are permitted if they did not lead to treatment discontinuation
- •No other lines of therapy that are available
排除标准
- •Enrolled in any other interventional clinical trial, starting within 4 weeks of the first dose of GIM-122 and throughout the duration of the study, or is receiving other therapy directed at their malignancy
- •Women who are pregnant or breastfeeding
- •History of cardiac issues, pulmonary embolism, active and clinically significant bacterial, fungal, or viral infection ≤ 6 months prior to dosing
- •Contraindications to the imaging assessments or other study procedures that subjects will undergo or any medical or social condition that, in the opinion of the investigator, might place a subject at an increased risk, affect compliance, or confound safety or other clinical study data interpretation Cancer Specific
- •Current second malignancy at other sites
- •Leptomeningeal disease
- •Spinal cord compression
- •Symptomatic or new or enlarging central nervous system (CNS) metastases
- •Treatment-specific Exclusion Criteria
- •Ongoing toxicity > Grade 1 from prior therapy according to Common Terminology Criteria for Adverse Events (CTCAE) v 5.0
- •Has undergone a major surgery < 1 month prior to administration of GIM-122
- •Has received radiation therapy within 2 weeks prior to administration of GIM-122
- •Has undergone or is anticipated to undergo organ transplantation including allogeneic or autologous stem cell transplantation at any time
- •Has received systemic anti-cancer therapy within 2 weeks and cytotoxic agents that have a major delayed toxicity within 4 weeks, of the first dose of GIM-122
- •Prior treatment with other immune modulating agents within < 4 weeks prior to the first dose of GIM-
- •Has a diagnosis of immunodeficiency, either primary or acquired
- •Has received treatment with systemic steroids or any form of immunosuppressive therapy within 14 days prior to administration of GIM-122
- •Has active or prior history of autoimmune disease, including ulcerative colitis and Crohn's disease, or any condition that requires systemic steroids.
- •Has a known severe intolerance to or hypersensitivity reactions to monoclonal antibodies, Fc-bearing proteins, or IV immunoglobulin preparations; prior history of human anti-human antibody response; known allergy to any of the study medications, or excipients in the various formulations of any agent.
- •Has received live vaccines within 30 days of study initiation (inactivated vaccines are allowed; seasonal vaccines should be up to date > 30 days prior to administration of GIM-122).
研究组 & 干预措施
Intravenous administration of GIM-122
GIM-122
干预措施: GIM122 (Drug)
结局指标
主要结局
Recommended Phase 2 Dose [RP2D] of GIM-122
时间窗: 18 Months
To identify Recommended Phase 2 Dose \[RP2D\] of GIM-122
Maximum tolerated dose [MTD] of GIM-122
时间窗: 18 months
To identify maximum tolerated dose \[MTD\] of GIM-122
Overall response rate (ORR) -Part B of the study
时间窗: 36 months
To identify overall response rate (ORR) in patients with advanced malignant tumors who are refractory/ resistant to PD-1 and PD-L1 therapy
Dose limiting toxicities [DLT] with GIM-122
时间窗: 18 months
To identify dose limiting toxicities \[DLT\] with GIM-122
Anti-tumor activity of GIM-122
时间窗: 36 months
To assess anti-tumor activity of GIM-122 as a single agent in patients with advanced malignant tumors who are refractory/ resistant to PD-1 and PD-L1 therapy
Incidence and severity of AE / SAEs and tolerability
时间窗: 36 months
To assess incidence and severity of AE / SAEs and tolerability assessed by CTCAE grading
次要结局
- Best overall response (BOR)(36 months)
- Overall survival (OS) rates at 12 months(36 months)
- Time of peak plasma concentration (Tmax)(36 months)
- Overall Response Rate (ORR) - Part A of the study(36 months)
- Tumor expression of immunological markers(36 months)
- Area under the plasma concentration versus time curve (AUC)(36 months)
- Peak Plasma Concentration (Cmax)(36 months)
- Progression-free survival (PFS)(36 months)
- Duration of response (DOR)(36 months)
- Disease control rate (DCR)(36 months)