Dose Escalation and Expansion of BBO-10203 in Advanced Solid Tumors (BREAKER-101)

Trial Title: Dose Escalation and Expansion of BBO-10203 in Advanced Solid Tumors (BREAKER-101)

NCT ID: NCT06625775

Condition: 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

Conditions: Official terms:
Neoplasms
Breast Neoplasms
Lung Neoplasms
Colorectal Neoplasms
Trastuzumab

Conditions: 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

Study type: Interventional

Study phase: Phase 1

Overall status: Recruiting

Study design:

Allocation: Non-Randomized

Intervention model: Sequential Assignment

Intervention model description: Phase 1a: sequential/parallel, Phase 1b: parallel

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Drug
Intervention name: BBO-10203
Description: Participants will receive assigned dose of BBO-10203 orally (PO) QD
Arm group label: Cohort 1a - Monotherapy Dose Escalation/Cohort Expansion
Arm group label: Cohort 1b - BBO-10203 Combination Dose Expansion
Arm group label: Combination Dose Escalation

Intervention type: Drug
Intervention name: Trastuzumab
Description: Participants will receive trastuzumab infusion (IV) or subcutaneous (SC)
Arm group label: Cohort 1b - BBO-10203 Combination Dose Expansion
Arm group label: Combination Dose Escalation

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.

Criteria for 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

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Locations:

Facility:
Name: Massachusetts General Hospital

Address:
City: Boston
Zip: 02114
Country: United States

Status: Recruiting

Facility:
Name: SCRI Oncology Partners

Address:
City: Nashville
Zip: 37203
Country: United States

Status: Recruiting

Facility:
Name: Mary Crowley Cancer Research

Address:
City: Dallas
Zip: 75230
Country: United States

Status: Recruiting

Start date: October 29, 2024

Completion date: November 2028

Lead sponsor:
Agency: TheRas, Inc., d/b/a BridgeBio Oncology Therapeutics
Agency class: Industry

Source: TheRas, Inc., d/b/a BridgeBio Oncology Therapeutics

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT06625775