A Phase 1a/1b Open-Label Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Efficacy of BBO-8520 in Subjects With Advanced KRASG12C Mutant Non-Small Cell Lung Cancer - The ONKORAS-101 Study
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 350
- 试验地点
- 43
- 主要终点
- Adverse Events
研究概览
简要总结
A first in human study to evaluate the safety and preliminary antitumor activity of BBO-8520, a KRAS G12C (ON and OFF) inhibitor, as a single agent and in combination with pembrolizumab and BBO-10203 in subjects with locally advanced and unresectable or metastatic non-small cell lung cancer with a KRAS (Kirsten rat sarcoma) G12C mutation.
详细描述
This is an open-label, multi-center, Phase 1 study designed to evaluate the safety, tolerability, pharmacokinetics, and efficacy of BBO-8520, a direct inhibitor of KRASG12C (ON and OFF), alone and in combination with the ICI pembrolizumab and BBO-10203 in subjects with locally advanced and unresectable or metastatic non-small cell lung cancer with a KRAS (Kirsten rat sarcoma) G12C mutation. The study includes dose escalation phase and dose expansion phase
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 documented locally advanced and unresectable or metastatic non-small cell lung cancer with a KRAS G12C mutation
- •Measurable disease by RECIST v1.1
- •Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1
排除标准
- •Patients with malignancy within the last 2 years as specified in the protocol
- •Patients with untreated or unstable brain metastases
- •Patients with known hypersensitivity to BBO-8520 or its excipients
- •For Cohorts 1b and 2b:
- •Patients with a known hypersensitivity to pembrolizumab or its excipients
- •Patients with active autoimmune disease of history of autoimmune disease that might recur
- •Patients with a history of interstitial lung disease/pneumonitis that required steroids, or current interstitial lung disease/pneumonitis
- •Other inclusion/exclusion criteria may apply
研究组 & 干预措施
Cohort 1b - Dose Escalation/Dose Finding Combination Therapy
Participants enrolled in this cohort will receive BBO-8520 (different dose levels will be evaluated) once a day (QD) in combination with pembrolizumab infusion (IV)
干预措施: BBO-8520 (Drug)
Cohort 2b - Dose Expansion Combination Therapy
Participants enrolled in this cohort will receive BBO-8520 once a day (QD) in combination with pembrolizumab infusion (IV)
干预措施: BBO-8520 (Drug)
Cohort 1b - Dose Escalation/Dose Finding Combination Therapy
Participants enrolled in this cohort will receive BBO-8520 (different dose levels will be evaluated) once a day (QD) in combination with pembrolizumab infusion (IV)
干预措施: Pembrolizumab (Drug)
Cohort 1b Safety Lead-In - Dose Expansion Doublet Combination Therapy
Participants enrolled in this cohort will receive BBO-8520 once a day (QD) in combination with BBO-10203 once a day (QD)
干预措施: BBO-8520 (Drug)
Cohort 1b - Dose Expansion Triplet Combination Therapy
Participants enrolled in this cohort will receive BBO-8520 once a day (QD) in combination with BBO-10203 once a day (QD) and pembrolizumab infusion (IV)
干预措施: BBO-10203 (Drug)
Cohort 1b - Dose Expansion Doublet Combination Therapy
Participants enrolled in this cohort will receive BBO-8520 once a day (QD) in combination with BBO-10203 once a day (QD)
干预措施: BBO-8520 (Drug)
Cohort 1a - Dose Escalation/Dose Finding Monotherapy
Participants enrolled in this cohort will receive BBO-8520 (different dose levels will be evaluated) once a day (QD) as monotherapy
干预措施: BBO-8520 (Drug)
Cohort 1b Safety Lead-In - Dose Expansion Doublet Combination Therapy
Participants enrolled in this cohort will receive BBO-8520 once a day (QD) in combination with BBO-10203 once a day (QD)
干预措施: BBO-10203 (Drug)
Cohort 1b - Dose Expansion Doublet Combination Therapy
Participants enrolled in this cohort will receive BBO-8520 once a day (QD) in combination with BBO-10203 once a day (QD)
干预措施: BBO-10203 (Drug)
Cohort 1b Safety Lead-In - Dose Expansion Triplet Combination Therapy
Participants enrolled in this cohort will receive BBO-8520 once a day (QD) in combination with BBO-10203 once a day (QD) and pembrolizumab infusion (IV)
干预措施: Pembrolizumab (Drug)
Cohort 1b - Dose Expansion Triplet Combination Therapy
Participants enrolled in this cohort will receive BBO-8520 once a day (QD) in combination with BBO-10203 once a day (QD) and pembrolizumab infusion (IV)
干预措施: Pembrolizumab (Drug)
Cohort 1b - Dose Expansion Triplet Combination Therapy
Participants enrolled in this cohort will receive BBO-8520 once a day (QD) in combination with BBO-10203 once a day (QD) and pembrolizumab infusion (IV)
干预措施: BBO-8520 (Drug)
Cohort 2a - Dose Expansion Monotherapy
Participants enrolled in this cohort will receive BBO-8520 once a day (QD) as monotherapy
干预措施: BBO-8520 (Drug)
Cohort 1b Safety Lead-In - Dose Expansion Triplet Combination Therapy
Participants enrolled in this cohort will receive BBO-8520 once a day (QD) in combination with BBO-10203 once a day (QD) and pembrolizumab infusion (IV)
干预措施: BBO-8520 (Drug)
Cohort 2b - Dose Expansion Combination Therapy
Participants enrolled in this cohort will receive BBO-8520 once a day (QD) in combination with pembrolizumab infusion (IV)
干预措施: Pembrolizumab (Drug)
Cohort 1b Safety Lead-In - Dose Expansion Triplet Combination Therapy
Participants enrolled in this cohort will receive BBO-8520 once a day (QD) in combination with BBO-10203 once a day (QD) and pembrolizumab infusion (IV)
干预措施: BBO-10203 (Drug)
结局指标
主要结局
Adverse Events
时间窗: approximately 3 years
Incidence and severity of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs)
Dose-limiting toxicities (DLTs)
时间窗: approximately 3 years
Number of participants with dose limiting toxicities
次要结局
- Overall Survival (OS)(approximately 3 years)
- To evaluate preliminary antitumor activity of BBO-8520(approximately 3 years)
- To characterize the pharmacokinetics (PK) of BBO-8520(approximately 3 years)