Clinical trial NCT06625775: Dose Escalation and Expansion of BBO-10203 in Advanced Solid Tumors (BREAKER-101)
Official title: A Phase 1a/1b Study of the PI3Kα:RAS Breaker BBO-10203 in Subjects With Advanced Solid Tumors (The BREAKER-101 Study)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Solid Tumor, Adult
Metastatic Breast Cancer
Advanced Breast Cancer
HER2 Mutation-Related Tumors
HER2-positive Metastatic Breast Cancer
HER2-Positive Advanced Breast Cancer
KRAS Mutant Metastatic Colorectal Cancer
Metastatic Lung Cancer
Metastatic Colorectal Cancer
Advanced Lung Cancer
Keywords: BREAKER-101
BridgeBio Oncology Therapeutics
BBOT
Phase1
Phase 1a/1b
Trastuzumab
Breast
Colorectal
Non-Small Cell Lung Cancer
CRC
NSCLC
HER2+
HER2-Positive
HR+
HER2-
HER2-Negative
Metastatic Cancer
Advanced Cancer
HR-Positive
Lead sponsor: TheRas, Inc., d/b/a BBOT (BridgeBio Oncology Therapeutics)
Sponsor class: INDUSTRY
First posted: 2024-10-03
Enrollment: 153
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Phase 1a: sequential/parallel, Phase 1b: parallel
Primary purpose: TREATMENT

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 phase.

Eligibility criteria: 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.

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

Primary outcomes:
measure: Determination of maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of BBO-10203 as a single agent
timeFrame: Up to approximately 5 years
measure: Percentage of patients with treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and dose-limiting toxicities (DLTs)
timeFrame: Up to approximately 5 years
measure: Recommended BBO-10203 dose in combination with trastuzumab
timeFrame: Up to approximately 5 years
Secondary outcomes:
measure: Clinical benefit rate (CBR) as assessed by RECIST v1.1.
timeFrame: Up to approximately 5 years
measure: Duration of response (DOR) as assessed by RECIST v1.1.
timeFrame: Up to approximately 5 years
measure: Progression-free survival (PFS) as assessed by RECIST v1.1
timeFrame: Up to approximately 5 years
measure: Overall survival (OS)
timeFrame: Up to approximately 5 years
measure: Area under the concentration-time curve (AUC
timeFrame: Predose (within 30 minutes) of C1D1 until up to approximately 5 years
measure: Maximum plasma drug concentration (Cmax)
timeFrame: Predose (within 30 minutes) of C1D1 until up to approximately 5 years
measure: Time for maximum plasma drug concentration (Tmax)
timeFrame: Predose (within 30 minutes) of C1D1 until up to approximately 5 years
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of California Los Angeles
state: California
city: Indianapolis
country: United States
facility: Indiana University Simon Comprehensive Cancer Center
state: Indiana
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Insitute
state: Massachusetts
city: New York
country: United States
facility: Columbia University Irving Medical Center
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Nashville
country: United States
facility: SCRI Oncology Partners
state: Tennessee
city: Dallas
country: United States
facility: Mary Crowley Cancer Research
state: Texas
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: Randwick
country: Australia
facility: Scientia Clinical Research
state: New South Wales
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre
state: Victoria
Study officials:
References: