A Phase I/II, Open-Label, Multi-Center, Dose Escalation and Cohort Expansion Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Antitumor Activity of INV-8989 in Patients With Advanced Solid Tumors Harboring KRAS G12D Mutations
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 178
- 试验地点
- 1
研究概览
简要总结
This is a Phase 1 and Phase 2 study to evaluate the safety, tolerability, pharmacokinetics, and preliminary antitumor activity of INV-8989 in patients with advanced solid tumors harboring KRAS G12D mutations.
详细描述
This is a Phase 1 and Phase 2 study to evaluate the safety, tolerability, pharmacokinetics, and preliminary antitumor activity of INV-8989 in patients with advanced solid tumors harboring KRAS G12D mutations.
The entire study consists of two parts: Phase 1 for dose escalation and Phase 2 for dose expansion and indication exploration.
Phase 1 dose escalation of INV-8989 follows a real time monitored, PK/PD and safety guided scheme with an accelerated titration plus traditional 3+3 design for DLT assessment.
Phase 2 aims to reassure the safety profile and better define efficacy. Phase 2 consists of Phase 2a and Phase 2b.
Phase 2a study aims to further confirm the safety profile of INV-8989 through a larger number of patients, clarify its PK characteristics and preliminary efficacy, and optimize the recommended Phase 2 dose (RP2D).
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
- •Written informed consent obtained.
- •Adult patients aged ≥ 18 years.
- •Patients with histologically or cytologically confirmed locally advanced, unresectable, or metastatic solid tumors harboring the KRAS G12D mutations.
- •Agree to provide available archived FFPE tumor tissue specimens or voluntarily accept pre-treatment tumor biopsy.
- •Have RECIST 1.1-defined measurable lesions.
- •Has a life expectancy of > 3 months.
- •ECOG performance status 0-
- •Adequate marrow, liver and kidney function.
- •Meet the study's specified contraceptive requirements.
- •Meet protocol-specified washout period requirements.
排除标准
- •Have protocol-defined toxicities within 28 days before the start of study treatment.
- •Have a second primary malignancy.
- •Patients with known hypersensitivity to the study drug or any of its components.
- •Prior history of receiving targeted therapy with specific KRAS G12D inhibitors/degraders or pan-RAS inhibitors/degraders for KRAS G12D mutation.
- •Has undergone major surgery within 28 days prior to the first dose of study drug.
- •Patients with symptomatic brain or leptomeningeal metastases.
- •Patients with other severe and persistent underlying medical conditions as assessed by the Investigator.
- •Have protocol-defined clinically significant cardiovascular diseases.
- •Prolonged QTcF interval.
- •Patients with dyspnea at rest secondary to complications of advanced malignancy, or requiring continuous oxygen therapy due to other medical conditions.
- •Patients with active pulmonary tuberculosis (TB).
- •Patients with a known history of interstitial lung disease (ILD).
- •Patients with a known history of allogeneic solid organ transplantation or allogeneic hematopoietic stem cell transplantation.
- •Have experienced a severe concurrent infection within 28 days prior to the first dose of study drug.
- •Patients with congenital or acquired immunodeficiency.
- •Female patients in pregnancy or lactation period.
- •Patients with concomitant diseases or conditions deemed by the Investigator likely to interfere with protocol compliance.
- •Patients unwilling or unable to comply with protocol-specified procedures.
研究组 & 干预措施
Phase 2b INV-8989 cohort C
干预措施: INV-8989 (Drug)
Phase 2b INV-8989 cohort D
干预措施: INV-8989 (Drug)
Phase 1 INV-8989 Dose escalation Dose level 5
干预措施: INV-8989 (Drug)
Phase 1 INV-8989 Dose escalation Dose level 6
干预措施: INV-8989 (Drug)
Phase 1 INV-8989 Dose escalation Dose level 7
干预措施: INV-8989 (Drug)
Phase 1 INV-8989 Dose escalation Dose level 1
干预措施: INV-8989 (Drug)
Phase 1 INV-8989 Dose escalation Dose level 2
干预措施: INV-8989 (Drug)
Phase 1 INV-8989 Dose escalation Dose level 3
干预措施: INV-8989 (Drug)
Phase 1 INV-8989 Dose escalation Dose level 8
干预措施: INV-8989 (Drug)
Phase 2a INV-8989 Dose level 1
干预措施: INV-8989 (Drug)
Phase 2a INV-8989 Dose level 2
干预措施: INV-8989 (Drug)
Phase 2b INV-8989 cohort A
干预措施: INV-8989 (Drug)
Phase 2b INV-8989 cohort B
干预措施: INV-8989 (Drug)
Phase 1 INV-8989 Dose escalation Dose level 4
干预措施: INV-8989 (Drug)