A Phase 1/2a Study of IMM-6-415 in Participants With Advanced or Metastatic Malignancies Harboring RAS or RAF Oncogenic Mutations
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 30
- 试验地点
- 5
- 主要终点
- Phase 1: Dose-Limiting Toxicities (DLT)
研究概览
简要总结
This is a FIH, ascending dose study to characterize the safety, tolerability, optimal dose and preliminary anti-tumor activity of IMM-6-415 in participants with advanced or metastatic solid tumors harboring RAS or RAF oncogenic mutations.
详细描述
The dose exploration will identify the candidate recommended Phase 2 dose (RP2D) of IMM-6-415 to further explore the anti-tumor activity of IMM-6-415 as monotherapy in Phase 2a tumor-specific cohorts. Patients will be self-administering IMM-6-415 on a daily basis for up to 16 cycles (21-day cycles). During the first 2 cycles, PK and PD will be assessed. Solid tumor types with RAS/RAF mutations are eligible.
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
- •Age ≥18 years
- •Life expectancy >16 weeks
- •Part 1: Histologically or cytologically confirmed diagnosis of a locally advanced unresectable or metastatic solid tumor malignancy harboring RAS (NRAS, KRAS, or HRAS)- or RAF- (ARAF, BRAF, RAF1) activating mutations, as documented by genomic analysis. Results of mutation analysis must be available prior to participant enrollment. A prior genomics report from archival tissues or liquid biopsy demonstrating mutation is acceptable
- •Part 2: Histologically or cytologically confirmed diagnosis of one of the following locally advanced unresectable or metastatic solid tumor malignancies: pancreatic adenocarcinoma, RASmut melanoma, Class I BRAFmut melanoma, RASmut NSCLC, other RASmut GI cancers (aside from CRC) or any other RAFmut solid tumor as documented by genomic analysis. Results of mutation analysis must be available prior to participant enrollment. A prior genomics report from archival tissues or liquid biopsy demonstrating mutation is acceptable
- •Participants must have received at least 1 line of systemic standard-of-care treatment for their advanced or metastatic disease and in the assessment of the Investigator, would be unlikely to tolerate or derive clinically meaningful benefit from other treatment options
- •Participants previously treated with codon-specific inhibitors of KRAS (including investigational agents) are eligible
- •KRASG12C mutant participants must have received prior treatment with a KRASG12C inhibitor for any approved indication
- •Radiologic evidence of measurable disease (i.e., at least 1 target lesion) according to RECIST 1.1 criteria
- •ECOG performance status 0 or
- •Participant has adequate organ function
排除标准
- •Inability to swallow oral medications.
- •Symptomatic, untreated, or actively progressing known central nervous system metastases.
- •Uncontrolled pleural or pericardial effusion or ascites requiring repeated drainage more than once every 28 days. In dwelling catheters are allowed.
- •History of severe COVID-19 infection resulting in current need of supplemental O2 therapy to maintain resting oxygen saturations ≥90%.
- •Presence of ongoing toxicities related to prior anticancer therapy that have not resolved to Grade ≤1 and are not otherwise allowed
- •Impaired cardiac function or clinically significant cardiac disease
- •Uncontrolled intercurrent illness including but not limited to poorly controlled diabetes or any medical condition determined by the Investigator to be a risk
- •History or concurrent evidence of retinal vein occlusion (RVO) or current risk factors for RVO. History of clinically significant serous retinopathy, central serous chorioretinopathy or retinal edema.
- •History of rhabdomyolysis within 3 months prior to Study Day 1
- •HIV-infected participant must be on anti-retroviral therapy and have a well-controlled HIV infection/disease
- •Participants with a history of HBV infection no longer requiring treatment are eligible; participants with a history of HCV infection are eligible if HCV viral load is undetectable at screening.
- •Females who are pregnant, breastfeeding, or planning to become pregnant and males who plan to father a child while enrolled in this study.
研究组 & 干预措施
IMM-6-415
Dose Escalation and Dose Expansion
干预措施: IMM-6-415 (Drug)
结局指标
主要结局
Phase 1: Dose-Limiting Toxicities (DLT)
时间窗: The first 21 days of study treatment
Number of participants with dose-limiting toxicities
Phase 1: Area Under Plasma Concentration (AUC) Time Curve of IMM-6-415
时间窗: After 9 weeks (3 Cycles) of study treatment
AUC0-t
Phase 1: Pharmacodynamic (PD) Activity of IMM-6-415 Plasma Concentrations Over Time
时间窗: After 9 weeks (3 Cycles) of study treatment
Surrogate PD Biomarker Assay, pERK
Phase 2a: Overall Response Rate (ORR)
时间窗: After up to 48 weeks (16 cycles) of study treatment
The proportion of participants who achieve a best overall response (BOR) of complete response (CR) or partial response (PR), based on RECIST 1.1 criteria
Phase 1: Recommended Phase 2 Dose (RP2D) candidate
时间窗: Initiation of study treatment through 21 days (up to approximately 18 months)
Selection of candidate RP2D to take forward into Ph2a
Phase 1: Maximum Observed Plasma Concentration of IMM-6-415
时间窗: After 9 weeks (3 Cycles) of study treatment
Cmax
Phase 1: Time to Reach Maximum Observed Plasma Concentration of IMM-6-415
时间窗: After 9 weeks (3 Cycles) of study treatment
Tmax
Phase 1/2a: Adverse Events
时间窗: From treatment initiation through 30 days following the last IMM-6-415 dose
Number of participants with adverse events
次要结局
- Phase 2a: Duration of Response (DOR)(Up to approximately 2 years)
- Phase 2a: Area Under Plasma Concentration (AUC) Time Curve of IMM-6-415(After 9 weeks (3 Cycles) of study treatment)
- Phase 2a: Progression Free Survival (PFS)(Up to approximately 2 years)
- Phase 2a: Time to Reach Maximum Observed Plasma Concentration of IMM-6-415(After 9 weeks (3 Cycles) of study treatment)
- Phase 2a: Landmark 6-Month Survival(After 6 months of study participation)
- Phase 2a: Maximum Observed Plasma Concentration of IMM-6-415(After 9 weeks (3 Cycles) of study treatment)
- Phase 2a: Overall Survival (OS)(Up to approximately 2 Years)
- Phase 2a: Disease Control Rate (DCR)(After 12 weeks (4 Cycles) of study treatment)
- Phase 2a: Landmark 3-Month Survival(After 3 months of study participation.)