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

Purpose

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.

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

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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

Study Design

Phase
Phase 1
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Sequential Assignment
Intervention Model Description
Phase 1a: sequential/parallel, Phase 1b: parallel
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Cohort 1a - Monotherapy Dose Escalation/Cohort Expansion 		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.
  • Drug: BBO-10203
    Participants will receive assigned dose of BBO-10203 orally (PO) QD
Experimental
Cohort 1b - BBO-10203 Combination Dose Expansion 		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.
  • Drug: BBO-10203
    Participants will receive assigned dose of BBO-10203 orally (PO) QD
  • Drug: Trastuzumab
    Participants will receive trastuzumab infusion (IV) or subcutaneous (SC)
Experimental
Combination Dose Escalation 		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.
  • Drug: BBO-10203
    Participants will receive assigned dose of BBO-10203 orally (PO) QD
  • Drug: Trastuzumab
    Participants will receive trastuzumab infusion (IV) or subcutaneous (SC)

Recruiting Locations

Massachusetts General Hospital
Boston, Massachusetts 02114

More Details

Status
Recruiting
Sponsor
TheRas, Inc., d/b/a BridgeBio Oncology Therapeutics

Study Contact

BridgeBio Oncology Therapeutics
650-391-9740
Breaker-101ct.gov@bridgebiooncology.com

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.