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

TheRas, Inc., d/b/a BBOT (BridgeBio Oncology Therapeutics)

Status and phase: Enrolling; Phase 1

Conditions: Metastatic Colorectal Cancer; Solid Tumor, Adult; HER2-Positive Advanced Breast Cancer; HER2-positive Metastatic Breast Cancer; KRAS Mutant Metastatic Colorectal Cancer; Metastatic Breast Cancer; Advanced Lung Cancer; HER2 Mutation-Related Tumors; Metastatic Lung Cancer; Advanced Breast Cancer

Treatments: Drug: BBO-10203; Drug: Trastuzumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT06625775

TBBO10203-101

Details and patient eligibility

About

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.

Full 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.

Enrollment: 153 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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153 participants in 3 patient groups

Cohort 1a - Monotherapy Dose Escalation/Cohort Expansion

Experimental group

Description:

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.

Treatment:

Drug: BBO-10203

Cohort 1b - BBO-10203 Combination Dose Expansion

Experimental group

Description:

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.

Treatment:

Drug: Trastuzumab

Drug: BBO-10203

Combination Dose Escalation

Experimental group

Description:

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.

Treatment:

Drug: Trastuzumab

Drug: BBO-10203