A Phase 1 Multiple Expansion Cohort Trial of the SOS1 Inhibitor MRTX0902 in Patients With Advanced Solid Tumors Harboring Mutations in the KRAS MAPK Pathway
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 64
- 试验地点
- 18
- 主要终点
- Number of Patients who Experience Dose-Limiting Toxicity
研究概览
简要总结
This is a Phase 1, open-label, multicenter, study evaluating the safety, tolerability, PK, PD, and anti-tumor activity of MRTX0902 alone and in combination with MRTX849 (adagrasib) in patients with advanced solid tumor malignancy harboring mutations in the KRAS-MAPK pathways.
详细描述
This first-in-human clinical trial will begin with an exploration of MRTX0902 dose and regimen. Once safety experience and PK data are available for the monotherapy regimen, dose escalation of the combination of MRTX0902 and adagrasib will be initiated, and will include a separate preliminary food effect assessments on MRTX0902 PK in combination with adagrasib. As potentially viable regimens are identified, Phase 1b expansion cohorts may be implemented to ensure collection of sufficient safety and PK information.
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
- •Histologically confirmed diagnosis of a solid tumor malignancy with any of the following oncogenic mutations detected in tumor tissue or ctDNA by a sponsor-approved test:
- •MRTX0902 monotherapy: known KRAS mutations, known annotated recurrent activating SOS1, PTPN11, class III BRAF, or EGFR mutation, or known annotated recurrent inactivating NF1 mutation;
- •MRTX0902 and adagrasib combination therapy: KRAS G12C mutation.
- •Unresectable or metastatic disease
- •No available treatment with curative intent; standard treatment is not available or patient declines
- •Presence of tumor lesions to be evaluated per RECIST 1.
- •Phase 1 dose escalation, RECIST 1.1 measurable or evaluable disease
- •Presence of a tumor lesion amenable to mandatory biopsy for pharmacodynamic evaluation at baseline and on-study unless Sponsor-confirmed as medically unsafe or infeasible.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
- •Adequate organ function
排除标准
- •Active brain metastases or carcinomatous meningitis
- •Prior treatment with a KRAS G12C inhibitor (for Phase 1b expansion for MRTX0902 and adagrasib combination).
- •History of significant hemoptysis or hemorrhage within 4 weeks of the first dose of study treatment.
- •Major surgery within 4 weeks of first dose of study treatment
- •History of pneumonitis or interstitial lung disease
- •Ongoing need for medication with following characteristics: substrate of CYP3A; strong inducer or inhibitor or CYP3A and/or P-gp; strong inhibitors of BRCP and proton pump inhibitors
- •Cardiac abnormalities
- •History of intestinal disease, inflammatory bowel disease, major gastric surgery, or other gastrointestinal conditions (eg, uncontrolled nausea, vomiting, malabsorption syndrome) likely to alter absorption of study treatment or result in inability to swallow oral medications
研究组 & 干预措施
Phase 1/1B Monotherapy
Dose Escalation/Evaluation
干预措施: MRTX0902 (Drug)
Phase 1/1B Combination Therapy
Dose Escalation/Evaluation and Food Effect Assessment
干预措施: MRTX0902 (Drug)
Phase 1/1B Combination Therapy
Dose Escalation/Evaluation and Food Effect Assessment
干预措施: MRTX849 (Drug)
结局指标
主要结局
Number of Patients who Experience Dose-Limiting Toxicity
时间窗: 21 Days
Number of patients who experience a treatment-related adverse event
时间窗: Up to 2 years
次要结局
- Area under the plasma concentration versus time curve(Up to 4 days)
- Time to achieve maximal plasma concentration(Up to 4 days)
- Apparent volume of distribution when dosed orally(Up to 4 days)
- Apparent total plasma clearance when dosed orally(Up to 4 days)
- Maximum observed plasma concentration(Up to 4 days)
- Terminal elimination half-life(Up to 4 days)