A Phase 1a/1b Open-Label Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Efficacy of BBO-11818 in Subjects With Advanced KRAS Mutant Cancers
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 665
- 试验地点
- 19
- 主要终点
- Incidence and severity of treatment emergent adverse events (TEAEs), serious adverse events (SAEs), and dose-limiting toxicities (DLTs)
研究概览
简要总结
A first in human study to evaluate the safety and preliminary antitumor activity of BBO-11818, a pan-KRAS inhibitor, in subjects with locally advanced unresectable or metastatic KRAS mutant solid tumors.
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-11818, a pan-KRAS inhibitor, alone and in combination with pembrolizumab, pembrolizumab + cis/carboplatin + pemetrexed, cetuximab, cetuximab + mFOLFOX6, BBO-10203 + mFOLFOX6, BBO-10203 +cetuximab, mFOLFIRINOX, gemcitabine + nab-paclitaxel, or BBO-10203 in subjects with locally advanced unresectable or metastatic KRAS mutant solid tumors. The study includes a dose escalation phase and a 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 NSCLC, PDAC, CRC, or other solid tumor with KRAS G12A, G12C, G12D, G12S, or G12V mutation
- •Measurable disease by RECIST v1.1
- •Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1
- •Life expectancy >24 weeks
- •Adequate organ function
排除标准
- •Malignancy within the last 2 years as specified in the protocol
- •Untreated brain metastases
- •Other inclusion/exclusion criteria are specified in the protocol.
研究组 & 干预措施
Cohort 1a - Dose Escalation Monotherapy
Participants enrolled in this cohort will receive BBO-11818 as monotherapy
干预措施: BBO-11818 (Drug)
Cohort 1b - Dose Escalation Combination Therapy (Pembrolizumab)
Participants enrolled in this cohort will receive BBO-11818 in combination with pembrolizumab infusion (IV)
干预措施: BBO-11818 (Drug)
Cohort 1b - Dose Escalation Combination Therapy (Pembrolizumab)
Participants enrolled in this cohort will receive BBO-11818 in combination with pembrolizumab infusion (IV)
干预措施: Pembrolizumab (Drug)
Cohort 1c - Dose Escalation Combination Therapy (Pembrolizumab + Cis/carboplatin + Pemetrexed)
Participants enrolled in this cohort will receive BBO-11818 in combination with pembrolizumab infusion (IV), cis/carboplatin infusion (IV), and pemetrexed infusion (IV)
干预措施: BBO-11818 (Drug)
Cohort 1c - Dose Escalation Combination Therapy (Pembrolizumab + Cis/carboplatin + Pemetrexed)
Participants enrolled in this cohort will receive BBO-11818 in combination with pembrolizumab infusion (IV), cis/carboplatin infusion (IV), and pemetrexed infusion (IV)
干预措施: Pembrolizumab (Drug)
Cohort 1c - Dose Escalation Combination Therapy (Pembrolizumab + Cis/carboplatin + Pemetrexed)
Participants enrolled in this cohort will receive BBO-11818 in combination with pembrolizumab infusion (IV), cis/carboplatin infusion (IV), and pemetrexed infusion (IV)
干预措施: Platinum chemotherapy (cisplatin or carboplatin) (Drug)
Cohort 1c - Dose Escalation Combination Therapy (Pembrolizumab + Cis/carboplatin + Pemetrexed)
Participants enrolled in this cohort will receive BBO-11818 in combination with pembrolizumab infusion (IV), cis/carboplatin infusion (IV), and pemetrexed infusion (IV)
干预措施: Pemetrexed (Drug)
Cohort 1d - Dose Escalation Combination Therapy (Cetuximab)
Participants enrolled in this cohort will receive BBO-11818 in combination with cetuximab infusion (IV)
干预措施: BBO-11818 (Drug)
Cohort 1d - Dose Escalation Combination Therapy (Cetuximab)
Participants enrolled in this cohort will receive BBO-11818 in combination with cetuximab infusion (IV)
干预措施: Cetuximab (Drug)
Cohort 2a - Dose Expansion Monotherapy
Participants enrolled in this cohort will receive BBO-11818 as monotherapy
干预措施: BBO-11818 (Drug)
Cohort 2b - Dose Expansion Combination (Pembrolizumab)
Participants enrolled in this cohort will receive BBO-11818 in combination with pembrolizumab infusion (IV)
干预措施: BBO-11818 (Drug)
Cohort 2b - Dose Expansion Combination (Pembrolizumab)
Participants enrolled in this cohort will receive BBO-11818 in combination with pembrolizumab infusion (IV)
干预措施: Pembrolizumab (Drug)
Cohort 2c - Dose Expansion Combination Therapy (Pembrolizumab + Cis/carboplatin + Pemetrexed)
Participants enrolled in this cohort will receive BBO-11818 in combination with pembrolizumab infusion (IV), cis/carboplatin infusion (IV), and pemetrexed infusion (IV)
干预措施: BBO-11818 (Drug)
Cohort 2c - Dose Expansion Combination Therapy (Pembrolizumab + Cis/carboplatin + Pemetrexed)
Participants enrolled in this cohort will receive BBO-11818 in combination with pembrolizumab infusion (IV), cis/carboplatin infusion (IV), and pemetrexed infusion (IV)
干预措施: Pembrolizumab (Drug)
Cohort 2c - Dose Expansion Combination Therapy (Pembrolizumab + Cis/carboplatin + Pemetrexed)
Participants enrolled in this cohort will receive BBO-11818 in combination with pembrolizumab infusion (IV), cis/carboplatin infusion (IV), and pemetrexed infusion (IV)
干预措施: Platinum chemotherapy (cisplatin or carboplatin) (Drug)
Cohort 2c - Dose Expansion Combination Therapy (Pembrolizumab + Cis/carboplatin + Pemetrexed)
Participants enrolled in this cohort will receive BBO-11818 in combination with pembrolizumab infusion (IV), cis/carboplatin infusion (IV), and pemetrexed infusion (IV)
干预措施: Pemetrexed (Drug)
Cohort 2d - Dose Expansion Combination Therapy (Cetuximab)
Participants enrolled in this cohort will receive BBO-11818 in combination with cetuximab infusion (IV)
干预措施: BBO-11818 (Drug)
Cohort 2d - Dose Expansion Combination Therapy (Cetuximab)
Participants enrolled in this cohort will receive BBO-11818 in combination with cetuximab infusion (IV)
干预措施: Cetuximab (Drug)
Cohort 1e - Dose Escalation Combination Therapy (FOLFOX + Cetuximab)
Participants enrolled in this cohort will receive BBO-11818 in combination with cetuximab infusion (IV) and FOLFOX infusion (IV)
干预措施: BBO-11818 (Drug)
Cohort 1e - Dose Escalation Combination Therapy (FOLFOX + Cetuximab)
Participants enrolled in this cohort will receive BBO-11818 in combination with cetuximab infusion (IV) and FOLFOX infusion (IV)
干预措施: Cetuximab (Drug)
Cohort 1f - Dose Escalation Combination Therapy (NALIRIFOX)
Participants enrolled in this cohort will receive BBO-11818 in combination with NALIRIFOX infusion (IV)
干预措施: BBO-11818 (Drug)
Cohort 1g - Dose Escalation Combination Therapy (Gemcitabine + Nab-Paclitaxel)
Participants enrolled in this cohort will receive BBO-11818 in combination with Gemcitabine infusion (IV) and Nab-Paclitaxel infusion (IV)
干预措施: BBO-11818 (Drug)
Cohort 1g - Dose Escalation Combination Therapy (Gemcitabine + Nab-Paclitaxel)
Participants enrolled in this cohort will receive BBO-11818 in combination with Gemcitabine infusion (IV) and Nab-Paclitaxel infusion (IV)
干预措施: Gemcitabine (Drug)
Cohort 1g - Dose Escalation Combination Therapy (Gemcitabine + Nab-Paclitaxel)
Participants enrolled in this cohort will receive BBO-11818 in combination with Gemcitabine infusion (IV) and Nab-Paclitaxel infusion (IV)
干预措施: Nab-paclitaxel (Drug)
Cohort 2e - Dose Expansion Combination Therapy (FOLFOX + Cetuximab)
Participants enrolled in this cohort will receive BBO-11818 in combination with cetuximab infusion (IV) and FOLFOX infusion (IV)
干预措施: BBO-11818 (Drug)
Cohort 2e - Dose Expansion Combination Therapy (FOLFOX + Cetuximab)
Participants enrolled in this cohort will receive BBO-11818 in combination with cetuximab infusion (IV) and FOLFOX infusion (IV)
干预措施: Cetuximab (Drug)
Cohort 2f - Dose Expansion Combination Therapy (NALIRIFOX)
Participants enrolled in this cohort will receive BBO-11818 in combination with NALIRIFOX infusion (IV)
干预措施: BBO-11818 (Drug)
Cohort 2g - Dose Expansion Combination Therapy (Gemcitabine + Nab-Paclitaxel)
Participants enrolled in this cohort will receive BBO-11818 in combination with Gemcitabine infusion (IV) and Nab-Paclitaxel infusion (IV)
干预措施: BBO-11818 (Drug)
Cohort 2g - Dose Expansion Combination Therapy (Gemcitabine + Nab-Paclitaxel)
Participants enrolled in this cohort will receive BBO-11818 in combination with Gemcitabine infusion (IV) and Nab-Paclitaxel infusion (IV)
干预措施: Gemcitabine (Drug)
Cohort 2g - Dose Expansion Combination Therapy (Gemcitabine + Nab-Paclitaxel)
Participants enrolled in this cohort will receive BBO-11818 in combination with Gemcitabine infusion (IV) and Nab-Paclitaxel infusion (IV)
干预措施: Nab-paclitaxel (Drug)
结局指标
主要结局
Incidence and severity of treatment emergent adverse events (TEAEs), serious adverse events (SAEs), and dose-limiting toxicities (DLTs)
时间窗: approximately 5 years
Determine recommended dose of BBO-11818 in combination with pembrolizumab +/- cis/carboplatin + pemetrexed, or cetuximab +/- FOLFOX, NALIRIFOX, or Gemcitabine + Nab-paclitaxel
时间窗: approximately 5 years
次要结局
- Objective response rate (ORR) per RECIST v1.1 and CNS RECIST(approximately 5 years)
- Clinical benefit rate (CBR) per RECIST v1.1(approximately 5 years)
- Duration of Response (DOR) per RECIST v1.1(approximately 5 years)
- Progression-Free Survival (PFS) per RECIST v1.1(approximately 5 years)
- Overall Survival (OS)(approximately 5 years)
- Pharmacokinetics of BBO-11818, irinotecan, and SN-38: Maximum blood concentration (Cmax)(approximately 5 years)
- Pharmacokinetics of BBO-11818, irinotecan, and SN-38: Time to achieve Cmax (Tmax)(approximately 5 years)
- Pharmacokinetics of BBO-11818, irinotecan, and SN-38: Area under the concentration-time curve (AUC)(approximately 5 years)