Dose Escalation and Expansion of BBO-10203 in Advanced Solid Tumors (BREAKER-101)
Phase 1
Recruiting
- Conditions
- Interventions
- Registration Number
- NCT06625775
- Brief Summary
First in human study to evaluate the safety, tolerability, and pharmacokinetics (PK) of BBO-10203, a PI3Kα:RAS breaker, alone and in combination with trastuzumab in patients with advanced solid tumors.
- Detailed Description
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 in patients with locally advanced unresectable or metastatic (ie, advanced) solid tumors. The study includes a dose escalation phase, and an expansion ph...
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 153
Inclusion Criteria
- 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
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1
- Adequate LVEF assessed by ECHO or MUGA
- 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).
- Patients with HR-positive, HER2-negative aBC, KRAS mutant aCRC or aNSCLC: Must have progression on, or disease recurrence after, all available SoC treatments or in the opinion of the investigator, would be unlikely to tolerate or derive clinically meaningful benefit from appropriate SoC therapy.
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Exclusion Criteria
- Patients with HER2+ aBC who have had more than 1 prior line of therapy with an antibody-drug conjugate
- Patients with KRAS mutant aCRC who have BRAFV600E mutation, HER2amp, or dMMR/MSI-H tumors
- Patients with KRAS mutant aNSCLC who have tumors with other targetable driver mutations (eg, EGFR, anaplastic lymphoma kinase, ROS1/BRAF/RET/MET/EGFR exon20 insertion/NTRK/HER2)
- Patients with untreated brain metastases (exceptions apply for HER2+ aBC per protocol)
Other inclusion/exclusion criteria are specified in the protocol
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Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Cohort 1a - Monotherapy Dose Escalation/Cohort Expansion BBO-10203 Participants enrolled in this cohort will receive BBO-10203 tablets orally (different dose levels will be evaluated) once daily (QD) as monotherapy. This cohort will enroll patients with advanced breast cancer, advanced colorectal cancer, and advanced lung cancer. Cohort 1b - BBO-10203 Combination Dose Expansion BBO-10203 Participants enrolled in this cohort will receive BBO-10203 tablets orally QD in combination with trastuzumab IV (8mg/kg over 90 minutes on Cycle 1 Day 1, 6mg/kg over 30-90 minutes during subsequent cycles)/SC (600mg). This cohort will enroll patients with advanced breast cancer. Cohort 1b - BBO-10203 Combination Dose Expansion Trastuzumab Participants enrolled in this cohort will receive BBO-10203 tablets orally QD in combination with trastuzumab IV (8mg/kg over 90 minutes on Cycle 1 Day 1, 6mg/kg over 30-90 minutes during subsequent cycles)/SC (600mg). This cohort will enroll patients with advanced breast cancer. Combination Dose Escalation BBO-10203 Participants enrolled in this cohort will receive BBO-10203 tablets orally (different dose levels will be evaluated) QD in combination with trastuzumab IV (8mg/kg over 90 minutes on Cycle 1 Day 1, 6mg/kg over 30-90 minutes during subsequent cycles)/SC (600mg). This cohort will enroll patients with advanced breast cancer. Combination Dose Escalation Trastuzumab Participants enrolled in this cohort will receive BBO-10203 tablets orally (different dose levels will be evaluated) QD in combination with trastuzumab IV (8mg/kg over 90 minutes on Cycle 1 Day 1, 6mg/kg over 30-90 minutes during subsequent cycles)/SC (600mg). This cohort will enroll patients with advanced breast cancer.
- Primary Outcome Measures
Name Time Method Determination of maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of BBO-10203 as a single agent Up to approximately 5 years Percentage of patients with treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and dose-limiting toxicities (DLTs) Up to approximately 5 years Recommended BBO-10203 dose in combination with trastuzumab Up to approximately 5 years
- Secondary Outcome Measures
Name Time Method 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
Trial Locations
- Locations (4)
Peter MacCallum Cancer Centre
🇦🇺Melbourne, Victoria, Australia
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
SCRI Oncology Partners
🇺🇸Nashville, Tennessee, United States
Mary Crowley Cancer Research
🇺🇸Dallas, Texas, United States