Open-Label Study of BBO-10203 in Subjects With Advanced Solid Tumors

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; HR-positive, HER2-negative 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: Ribociclib; Drug: BBO-10203; Drug: FOLFOX; Drug: Fulvestrant; Drug: Bevacizumab; Drug: Trastuzumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT06625775

2024-519445-29-00 (EU Trial (CTIS) Number)

BREAKER-101 (Other Identifier)

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 other anti-cancer agents 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, 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.

Enrollment: 392 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 (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

Exclusion criteria

• 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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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392 participants in 5 patient groups

BBO-10203

Experimental group

Description:

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.

Treatment:

Drug: BBO-10203

BBO-10203 + Trastuzumab

Experimental group

Description:

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.

Treatment:

Drug: Trastuzumab

Drug: BBO-10203

BBO-10203 + Fulvestrant

Experimental group

Description:

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.

Treatment:

Drug: Fulvestrant

Drug: BBO-10203

Drug: Ribociclib

BBO10203 + Fulvestrant + Ribociclib

Experimental group

Description:

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.

Treatment:

Drug: Fulvestrant

Drug: BBO-10203

Drug: Ribociclib

BBO10203 + FOLFOX + Bevacizumab

Experimental group

Description:

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.

Treatment:

Drug: Bevacizumab

Drug: FOLFOX

Drug: BBO-10203