Phase 1/2 Open-label Study of BMS-986466 in Combination With Adagrasib With or Without Cetuximab in Participants With KRAS G12C-mutant Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 5
- 试验地点
- 9
- 主要终点
- Part 1: Number of Participants With Dose Limiting Toxicity (DLTs)
研究概览
简要总结
The purpose of this study is to find a safe, tolerable, and efficacious dose of BMS-986466 when given orally, in combination with adagrasib with or without cetuximab in participants with advanced KRAS G12C-mutant non-small cell lung cancer (NSCLC), pancreatic duct adenocarcinoma (PDAC), biliary tract cancer (BTC), or colorectal cancer (CRC).
研究设计
- 研究类型
- Interventional
- 分配方式
- 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
- •Key Inclusion Criteria:
- •Individuals with a confirmed diagnosis of advanced KRAS G12C mutant NSCLC, CRC, PDAC and BTC that has spread to other parts of the body and cannot be removed surgically, may or may not have received previous treatment with KRAS G12C inhibitors.
- •For NSCLC and CRC: Individuals must have a documented KRAS G12C mutation status from NYS or FDA approved/cleared or CE marked test or, when such result is not available, positive KRAS G12C mutation status should be confirmed by a central laboratory in blood sample collected at the time of screening.
- •For PDAC and BTC: Participants must have a documented KRAS G12Cmutation from NYS or FDA-approved/cleared, or CE-marked test and blood samples will be collected only for retrospective testing.
- •Are relapsed or refractory to available standard of care treatments.
- •Individuals with a confirmed diagnosis of advanced KRAS G12C-mutant NSCLC (Part 2A) or CRC (Part 2B) that has spread to other parts of the body and cannot be removed surgically and have not received previous treatment with KRAS inhibitors.
- •Individuals must have a documented KRAS G12C mutation from FDA or NYS approved/ cleared or CE marked test or, when such result is not available, positive KRAS G12C mutation status should be confirmed by a central laboratory in blood sample and /or tumor samples collected at the time of screening or from archival biopsies (less than 1 year old).
- •Have failed or disease recurrence or are not able to tolerate after at least 1 pervious line of therapy.
排除标准
- •Have tumors with known BARF V600X, PTPN11 or KRASQ61X mutations.
- •Have or any significant heart disease or condition.
- •Receiving any medications that are substrate of CYP3A4 or inducers and/ or inhibitors
- •Note: Other protocol-defined inclusion/exclusion criteria apply.
研究组 & 干预措施
Part 1: Dose Escalation
干预措施: Adagrasib (Drug)
Part 1: Dose Escalation
干预措施: Cetuximab (Drug)
Part 2: Dose Expansion
干预措施: BMS-986466 (Drug)
Part 1: DDI Cohort
干预措施: BMS-986466 (Drug)
Part 1: DDI Cohort
干预措施: Adagrasib (Drug)
Part 1: Dose Escalation
干预措施: BMS-986466 (Drug)
Part 2: Dose Expansion
干预措施: Adagrasib (Drug)
Part 2: Dose Expansion
干预措施: Cetuximab (Drug)
结局指标
主要结局
Part 1: Number of Participants With Dose Limiting Toxicity (DLTs)
时间窗: Cycle 1 (Each cycle consist of 28 days)
A DLT was defined as: * Death not related to disease progression * Grade (Gr) 4 (Life-threatening) neurotoxicity * Gr 3 (Severe) neurotoxicity of greater than 7 days * Gr 3 neurotoxicity does not revert to baseline within 28 days of the start date of the Grade 3 event * Seizures of grade that do not resolve within 7 days * Gr 4 cytokine release syndrome (CRS) that does not resolve to less than or equal to Gr 3 within 3 days * Gr 3 CRS that does not resolve to less than or equal to Grade 2 within 7 days * Any increase in aspartate aminotransferase (AST) or ALT \\\> 3 Ã- ULN and concurrent increase in total bilirubin \\\> 2 Ã- ULN that is unrelated to CRS and has no other probable reason to explain the combination of increases * Any other Gr 3 or 4 event deemed unexpected by the Investigator and considered a DLT upon evaluation by the safety review committee
Part 1: Number of Participants With Adverse Events (AEs)
时间窗: From first dose until 100 days after last dose (Up to approximately 5 months)
An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment.
Part 1: Number of Participants With Serious Adverse Events (SAEs)
时间窗: From first dose until 30 days after last dose (Up to approximately 3 months)
A SAE is defined as any untoward medical occurrence that, at any dose: results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability or permanent damage, is a congenital anomaly/birth defect, is an important medical event.
Part 1: Number of Participants With AEs Leading to Discontinuation
时间窗: From first dose until 30 days after last dose (Up to approximately 3 months)
An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatmen
Part 1: Number of Participants Who Died
时间窗: From first dose until 100 days after last dose (Up to approximately 5 months)
Death due to any cause was assessed.
Part 2 Objective Response Rate (ORR) Assessed by Blinded Independent Central Review (BICR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
时间窗: From randomization untill disease progression or death, whichever occurs first (up to approximately 5 months)
Objective Response Rate (ORR) is defined as the percentage of participants with a confirmed Best overall response of Complete Response (CR) or Partial Response (PR) by RECIST v1.1. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \\\< 10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
次要结局
- Part 1: Maximum Observed Plasma Concentration (Cmax)(Cycle 1 Day 1 (Each cycle consist of 28 days))
- Part 1: Time to Maximum Concentration (Tmax)(Cycle 1 Day 1 (Each cycle consist of 28 days))
- Part 1: Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC[0-T])(Cycle 1 Day 1 (Each cycle consist of 28 days))
- Part 2-Progression-free Survival (PFS) Assessed by BICR as Per RECIST v1.1(From randomization untill disease progression or death, whichever occurs first (up to approximately 5 months))
- Part 2- Disease Control Rate (DCR) Assessed by BICR as Per RECIST v1.1(From randomization untill disease progression or death, whichever occurs first (up to approximately 5 months))
- Part 2- Duration of Response (DOR) Assessed by BICR as Per RECIST v1.1(From randomization untill disease progression or death, whichever occurs first (up to approximately 5 months))
- Part 2- Time to Response (TTR)(From randomization untill disease progression or death, whichever occurs first (up to approximately 5 months))
- Part 2- Number of Participants With Adverse Events (AEs)(From first dose until 100 days after last dose (Up to approximately 5 months))
- Part 2- Number of Participants With Serious Adverse Events (SAEs)(From first dose until 100 days after last dose (Up to approximately 5 months))
- Part 2- Number of Participants With AEs Leading to Discontinuation(From first dose until 100 days after last dose (Up to approximately 5 months))
- Part 2- Number of Participants Who Died(From first dose until 100 days after last dose (Up to approximately 5 months))
- Part 1a and 1b - Changes From Baseline in Pharmacodynamic Biomarker(Baseline and Cycle 1 Day 1 (Each cycle consist of 28 days))