A Phase 1/2, Open-Label, Dose-Escalation, Dose-Enrichment, and Dose-Expansion Trial to Evaluate the Safety, Tolerability, Pharmacokinetics, and Antitumor Activity of BLU-924 (SAR449336) as Monotherapy and Combination Therapy in Participants With Advanced Pancreatic Cancer, Non-Small Cell Lung Cancer, or Colorectal Cancer Harboring KRAS Mutations
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 265
- 试验地点
- 16
- 主要终点
- Dose Escalation and Enrichment: Percentage of Participants with Dose-limiting Toxicity (DLTs)
研究概览
简要总结
A first in human study to evaluate the safety, tolerability, pharmacokinetics, and antitumor activity of BLU-924 / SAR449336, a pan-KRAS inhibitor, in participants with advanced Pancreatic Cancer, Non-Small Cell Lung Cancer, or Colorectal Cancer harboring KRAS mutations.
详细描述
This is an open-label, multi-center, Phase 1/2 study designed to evaluate the safety, tolerability, pharmacokinetics (PK), and efficacy of BLU-924, a pan-KRAS inhibitor, in participants with metastatic KRAS mutant pancreatic ductal adenocarcinoma (PDAC), non-small cell lung cancer (NSCLC), or colorectal cancer (CRC). The monotherapy part of the study includes Dose Escalation, Dose Enrichment, and Dose Expansion. Participants enrolled during Dose Escalation and Dose Enrichment will be evaluated for dose limiting toxicities (DLTs) to determine the MTD. Participants enrolled into disease-specific Enrichment cohorts will enable a more robust characterization of safety, PK, pharmacodynamics, and preliminary clinical activity. Enrolment into Dose Expansion will follow the identification of at least 1 recommended dose for expansion (RDFE) based on data from the Dose Escalation and Dose Enrichment. No combination arm is active at this time.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 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
- •Pathologically confirmed diagnosis of metastatic Kirsten rat sarcoma viral oncogene homolog (KRAS)-mutant pancreatic ductal adenocarcinoma (PDAC), non-small cell lung cancer (NSCLC), or colorectal cancer (CRC) with evidence of a single KRAS G12C, G12D, G12V, G12A, G12S, or G13D mutation in tumor tissue or circulating tumor deoxyribonucleic acid (ctDNA).
- •Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) v1.
- •Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-
- •Patients must have received all standard therapies for their cancer type in the metastatic setting, unless they are unable to receive such therapies due to clinical characteristics, comorbidities, or other medically justified reasons.
排除标准
- •History of additional malignancy within the last 2 years, with some exceptions as specified in the protocol.
- •Active brain metastases (participants with asymptomatic brain metastases may be eligible).
- •Have received prior targeted treatment(s) against KRAS, including pan-KRAS inhibitors, multi-RAS inhibitors, mutant-selective KRAS inhibitors, and RAS or KRAS degraders.
- •Active or uncontrolled systemic infection, such as tuberculosis, Hepatitis B virus (HBV), Hepatitis C virus (HCV), or Human immunodeficiency virus (HIV).
- •The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
研究组 & 干预措施
Monotherapy Part: BLU-924 Dose Escalation, Dose Enrichment, and Dose Expansion
Participants will receive BLU-924 oral tablet, once daily as monotherapy during Dose Escalation followed by Dose Enrichment.
During Dose Enrichment, participants with PDAC, NSCLC or CRC will receive BLU-924 at selected dose levels below the current escalation dose or, if Dose Escalation is complete, below the MTD.
During Dose Expansion, participants will receive RDFE of BLU-924 oral tablet, once daily as monotherapy determined during escalation monotherapy part.
Dose Expansion may be initiated to further assess the safety, antitumor activity, PK, and pharmacodynamics of BLU-924 at RDFE in indication-specific cohorts (PDAC, NSCLC, or CRC) harboring a KRAS mutation.
干预措施: BLU-924 (Drug)
结局指标
主要结局
Dose Escalation and Enrichment: Percentage of Participants with Dose-limiting Toxicity (DLTs)
时间窗: Up to 5 years
Any of the prespecified AEs that are attributable to the study treatment, occurring in the DLT observation period are considered DLTs, excluding toxicities clearly due to underlying disease or extraneous causes.
Dose Escalation, Enrichment and Expansion: Incidence and Severity of Treatment-emergent Adverse Events (TEAEs) and Serious AEs
时间窗: Up to 5 years
An adverse event (AE) is any untoward medical occurrence in a participant who received study medication without regard to possibility of causal relationship to it.
Dose Escalation and Enrichment: Maximum Tolerated Dose (MTD) of BLU-924
时间窗: Up to 5 years
Dose Escalation and Enrichment: Recommended Dose for Expansion (RDFE) of BLU-924
时间窗: Up to 5 years
Dose Expansion: Overall Response Rate (ORR)
时间窗: Up to 5 years
次要结局
- Dose Escalation, Enrichment and Expansion: Cmax - Maximum Plasma Concentration for BLU-924(Up to 2 years)
- Dose Escalation, Enrichment and Expansion: Cmin - Minimum Plasma Concentration of BLU-924(Up to 2 years)
- Dose Escalation, Enrichment, and Expansion: Duration of Response (DOR)(Up to 5 years)
- Dose Escalation, Enrichment, and Expansion: Disease Control Rate (DCR)(Up to 5 years)
- Dose Escalation, Enrichment and Expansion: AUC - Area Under the Plasma Concentration Time Curve for BLU-924(Up to 2 years)
- Dose Escalation and Enrichment: Overall Response Rate (ORR)(Up to 5 years)
- Dose Escalation, Enrichment and Expansion: Progression-free Survival (PFS)(Up to 5 years)
- Dose Expansion: Overall Survival (OS)(Up to 5 years)
- Dose Escalation, Enrichment and Expansion: Tmax - Time to Maximum Plasma Drug Concentration for BLU-924(Up to 2 years)
- Dose Escalation, Enrichment and Expansion: t1/2 - Terminal Half-life of BLU-924(Up to 2 years)
- Dose Escalation, Enrichment and Expansion: CL/F - Apparent Oral Clearance of BLU-924(Up to 2 years)
- Dose Escalation, Enrichment and Expansion: Vc/F- Apparent Volume of Central Compartment of BLU-924(Up to 2 years)
- Dose Escalation, Enrichment and Expansion: Vd- Volume of Distribution of BLU-924(Up to 2 years)