A Phase 1a/1b Open-Label Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Efficacy of BBO-10203 in Subjects With Advanced Solid Tumors (The BREAKER-101 Study)
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 392
- 试验地点
- 59
- 主要终点
- Percentage of patients with treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and dose-limiting toxicities (DLTs)
研究概览
简要总结
First in human study to evaluate the safety, tolerability, and pharmacokinetics (PK) of BBO-10203, a PI3Kα:RAS breaker, alone and in combination with other anti-cancer agents in patients with advanced solid tumors.
详细描述
This is an open-label, multi-center Phase 1a/1b study designed to evaluate the safety, tolerability, preliminary antitumor activity, and PK of BBO-10203 as a single agent and in combination with Trastuzumab, Fulvestrant +/- Ribociclib, or FOLFOX + Bevacizumab in patients with locally advanced unresectable or metastatic (ie, advanced) solid tumors. The study includes a dose escalation phase and an expansion phase.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 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
- •Locally advanced and unresectable or metastatic HER2-positive advanced breast cancer (aBC), HR-positive/HER2-negative advanced breast cancer, KRAS mutant advanced colorectal cancer (aCRC), or KRAS mutant advanced non-small cell lung cancer (aNSCLC)
- •Measurable disease by RECIST v1.1 (except for HR-positive HER2-negative aBC where evaluable bone-only disease is permitted)
- •Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1
- •Adequate LVEF assessed by ECHO or MUGA (BBO-10203 + Trastuzumab cohorts only)
- •Stable brain metastases
- •Patients with HER2-positive aBC: Must have had at least 2 prior lines of anti-HER2-directed therapy. Only 1 prior line is acceptable where there is no other regionally available standard of care (SoC)
- •Monotherapy Cohort patients with HR-positive, HER2-negative aBC, KRAS mutant aCRC or aNSCLC: Must have progression on, or disease recurrence after at least one line of SOC treatment or in the opinion of the investigator, would be unlikely to tolerate or derive clinically meaningful benefit from SoC therapy
- •BBO-10203 + Fulvestrant combination cohort patients with HR-positive, HER2-negative aBC: confirmed PIK3CA mutation, must have been treated with a CDK4/6i
- •BBO-10203 + Fulvestrant + ribociclib combination cohort patients with HR-positive, HER2-negative aBC: confirmed PIK3CA mutation, no prior systemic therapy in the aBC setting permitted
- •BBO-10203 + FOLFOX + Bevacizumab combination cohort patients with KRAS mutant aCRC: One prior line of irinotecan-containing therapy for locally advanced or metastatic CRC is allowed but not required
排除标准
- •Patients with KRAS mutant aCRC who have KRAS G12R mutation, BRAFV600E mutation, HER2amp, or dMMR/MSI-H tumors
- •Patients with KRAS mutant aNSCLC who have KRAS G12R mutation, or tumors with other targetable driver mutations (eg, EGFR, anaplastic lymphoma kinase, ROS1/BRAF/RET/MET/EGFR exon20 insertion/NTRK/HER2)
- •Patients with untreated and/or non-stable brain metastases
- •Other inclusion/exclusion criteria are specified in the protocol
研究组 & 干预措施
BBO-10203
Participants enrolled in this cohort will receive BBO-10203 tablets orally (different dose levels will be evaluated) once daily as monotherapy. This cohort will enroll patients with HER2-positive advanced breast cancer, HR-positive HER2-negative advanced breast cancer, advanced colorectal cancer, and advanced lung cancer.
干预措施: BBO-10203 (Drug)
BBO-10203 + Trastuzumab
Participants enrolled in this cohort will receive BBO-10203 tablets orally in combination with trastuzumab. This cohort will enroll patients with HER2-positive advanced breast cancer.
干预措施: Trastuzumab (Drug)
BBO10203 + FOLFOX + Bevacizumab
Participants enrolled in this cohort will receive BBO-10203 tablets orally in combination with FOLFOX and bevacizumab. This cohort will enroll patients with KRAS-mutant advanced colorectal cancer.
干预措施: FOLFOX (Drug)
BBO10203 + FOLFOX + Bevacizumab
Participants enrolled in this cohort will receive BBO-10203 tablets orally in combination with FOLFOX and bevacizumab. This cohort will enroll patients with KRAS-mutant advanced colorectal cancer.
干预措施: BBO-10203 (Drug)
BBO-10203 + Fulvestrant
Participants enrolled in this cohort will receive BBO-10203 tablets orally in combination with fulvestrant. This cohort will enroll patients with HR-positive, HER2-negative advanced breast cancer.
干预措施: BBO-10203 (Drug)
BBO-10203 + Fulvestrant
Participants enrolled in this cohort will receive BBO-10203 tablets orally in combination with fulvestrant. This cohort will enroll patients with HR-positive, HER2-negative advanced breast cancer.
干预措施: Ribociclib (Drug)
BBO-10203 + Trastuzumab
Participants enrolled in this cohort will receive BBO-10203 tablets orally in combination with trastuzumab. This cohort will enroll patients with HER2-positive advanced breast cancer.
干预措施: BBO-10203 (Drug)
BBO10203 + Fulvestrant + Ribociclib
Participants enrolled in this cohort will receive BBO-10203 tablets orally in combination with fulvestrant and ribociclib as determined in the dose escalation. This cohort will enroll patients with HR-positive, HER2-negative advanced breast cancer.
干预措施: BBO-10203 (Drug)
BBO10203 + Fulvestrant + Ribociclib
Participants enrolled in this cohort will receive BBO-10203 tablets orally in combination with fulvestrant and ribociclib as determined in the dose escalation. This cohort will enroll patients with HR-positive, HER2-negative advanced breast cancer.
干预措施: Fulvestrant (Drug)
BBO10203 + Fulvestrant + Ribociclib
Participants enrolled in this cohort will receive BBO-10203 tablets orally in combination with fulvestrant and ribociclib as determined in the dose escalation. This cohort will enroll patients with HR-positive, HER2-negative advanced breast cancer.
干预措施: Ribociclib (Drug)
BBO10203 + FOLFOX + Bevacizumab
Participants enrolled in this cohort will receive BBO-10203 tablets orally in combination with FOLFOX and bevacizumab. This cohort will enroll patients with KRAS-mutant advanced colorectal cancer.
干预措施: Bevacizumab (Drug)
BBO-10203 + Fulvestrant
Participants enrolled in this cohort will receive BBO-10203 tablets orally in combination with fulvestrant. This cohort will enroll patients with HR-positive, HER2-negative advanced breast cancer.
干预措施: Fulvestrant (Drug)
结局指标
主要结局
Percentage of patients with treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and dose-limiting toxicities (DLTs)
时间窗: Up to approximately 5 years
Recommended BBO-10203 dose in combination with trastuzumab, fulvestrant +/- ribociclib, and FOLFOX + bevacizumab
时间窗: Up to approximately 5 years
Determination of maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of BBO-10203 as a single agent
时间窗: Up to approximately 5 years
次要结局
- Clinical benefit rate (CBR) as assessed by RECIST v1.1.(Up to approximately 5 years)
- Duration of response (DOR) as assessed by RECIST v1.1.(Up to approximately 5 years)
- Progression-free survival (PFS) as assessed by RECIST v1.1(Up to approximately 5 years)
- Overall survival (OS)(Up to approximately 5 years)
- Area under the concentration-time curve (AUC(Predose (within 30 minutes) of C1D1 until up to approximately 5 years)
- Maximum plasma drug concentration (Cmax)(Predose (within 30 minutes) of C1D1 until up to approximately 5 years)
- Time for maximum plasma drug concentration (Tmax)(Predose (within 30 minutes) of C1D1 until up to approximately 5 years)
- Objective response rate (ORR) as assessed by RECIST v1.1 for patients with measurable disease(Up to approximately 5 years)