A Phase 1/2, Open-label, Dose-escalation, Dose-optimization and Expansion Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Therapeutic Activity of GI-101/GI-101A as a Single Agent and in Combination With Pembrolizumab or Lenvatinib in Patients With Advanced or Metastatic Solid Tumors (Keynote B59)
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 317
- 试验地点
- 14
- 主要终点
- Incidence and nature of Dose-Limiting Toxicity (DLTs), Incidence, nature, and severity of adverse events (AEs) and immune-related AEs (irAEs)
研究概览
简要总结
The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, and therapeutic activity of GI-101/GI-101A as a single agent or in combination with pembrolizumab or lenvatinib over a range of advanced and/or metastatic solid tumors.
详细描述
This is a Phase 1/2, open-label, dose-escalation, dose-optimization and expansion study to evaluate safety, tolerability, pharmacokinetics, and therapeutic activity of GI-101/GI-101A as a single agent and in combination with pembrolizumab or lenvatinib in patients with advanced or metastatic solid tumors (Keynote B59)
This study will comprise six parts.
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Part A: Dose-escalation and expansion cohorts of GI-101 monotherapy
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Part B: Dose-escalation and expansion cohorts of GI-101 plus pembrolizumab
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Part C: Dose-optimization and expansion cohorts of GI-101 plus lenvatinib
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Part E: Dose-escalation cohorts of GI-101A monotherapy
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Part F: Dose-escalation cohorts of GI-101A plus pembrolizumab
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Part G: Dose-optimization and indication-specific cohorts of GI-101A plus pembrolizumab
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Part G1: Dose optimization cohorts in CPI-refractory urothelial cancer
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Part G2: Indication-specific cohorts in CPI-refractory ccRCC, squamous cell NSCLC and SoC-experienced MSS/pMMR CRC
GI-101/GI-101A is a novel bi-specific Fc fusion protein containing the CD80 ectodomain as an N-terminal moiety and an interleukin (IL)-2 variant as a C-terminal moiety configurated via a human immunoglobulin G4 (IgG4) Fc.
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
- •Males and females aged ≥ 18 years (or ≥ 19 years according to local regulatory guidelines) at the time of screening.
- •Has adequate organ and marrow function as defined in protocol.
- •Measurable disease as per RECIST v1.
- •ECOG performance status 0-
- •Adverse events related to any prior chemotherapy, radiotherapy, immunotherapy, other prior systemic anti-cancer therapy, or surgery must have resolved to Grade ≤1, except alopecia and Grade 2 peripheral neuropathy.
- •HIV infected patients must be on anti-retroviral therapy (ART) and have a well-controlled HIV infection/disease as defined in protocol.
排除标准
- •Has known active CNS metastases and/or carcinomatous meningitis.
- •An active second malignancy
- •Has active or a known history of Hepatitis B or known active Hepatitis C virus infection.
- •Has active tuberculosis or has a known history of active tuberculosis
- •Active or uncontrolled infections, or severe infection within 4 weeks before study treatment administration.
- •History of chronic liver disease or evidence of hepatic cirrhosis, except patients with liver metastasis.
- •Has an active autoimmune disease that has required systemic treatment in past 2 years.
- •Previous immunotherapies related to mode of action of GI-
- •Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive medications within 2 weeks prior to Cycle 1 Day
- •Administration of prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to treatment.
- •Radiotherapy within the last 2 weeks before start of study treatment administration, with exception of limited field palliative radiotherapy
- •Administration of a live, attenuated vaccine within 4 weeks before Cycle 1 Day
- •Known hypersensitivity to any of the components of the drug products and/or excipients of GI-101/GI-101A, pembrolizumab or lenvatinib.
- •Other protocol defined inclusion exclusion criteria may apply. Cancer type and part-specific inclusion criteria are described in the study protocol.
研究组 & 干预措施
GI-101 + Pembrolizumab
Dose escalation: GI-101, multiple ascending doses
Dose expansion:
干预措施: Pembrolizumab (KEYTRUDA®) (Drug)
GI-101 + Lenvatinib
Dose optimization:
Dose expansion:
干预措施: Lenvatinib (Drug)
GI-101A
Dose escalation: GI-101A, multiple ascending doses
干预措施: GI-101A (Drug)
GI-101 + Lenvatinib
Dose optimization:
Dose expansion:
干预措施: GI-101 (Drug)
GI-101
Dose escalation: GI-101, multiple ascending doses
Dose expansion:
干预措施: GI-101 (Drug)
GI-101 + Pembrolizumab
Dose escalation: GI-101, multiple ascending doses
Dose expansion:
干预措施: GI-101 (Drug)
GI-101A + Pembrolizumab
Dose escalation: GI-101A, multiple ascending doses Dose optimization Indication-specific cohorts
干预措施: Pembrolizumab (KEYTRUDA®) (Drug)
GI-101A + Pembrolizumab
Dose escalation: GI-101A, multiple ascending doses Dose optimization Indication-specific cohorts
干预措施: GI-101A (Drug)
结局指标
主要结局
Incidence and nature of Dose-Limiting Toxicity (DLTs), Incidence, nature, and severity of adverse events (AEs) and immune-related AEs (irAEs)
时间窗: Study Day 1, assessed up to approximately 24 months
Dose escalation and optimization phase of Part A, B, and C and Dose escalation phase of Part E and F
Objective Response Rate (ORR), Disease Control Rate (DCR) and Duration of Response (DoR) according to RECIST version 1.1
时间窗: Study Day 1, assessed up to approximately 24 months
Based on Central review (Part G1) and Investigator review (Part G2) of radiographic imaging in Part G1 Dose optimization cohorts, Part G2 Indication-specific cohorts ORR only; Based on Investigator review of radiographic imaging in dose expansion phase of Part A, B and C
次要结局
- Serum concentration of GI-101/GI-101A at specified timepoints(Study Day 1, assessed up to approximately 24 months)
- Anti-tumor activities(Study Day 1, assessed up to approximately 24 months)
- Incidence, nature, and severity of adverse events (AEs) graded according to CTCAE v5.0(Study Day 1, assessed up to approximately 24 months)