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

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 other anti-cancer agents 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
  • KRAS Mutant Metastatic Colorectal Cancer
  • Metastatic Lung Cancer
  • Metastatic Colorectal Cancer
  • Advanced Lung Cancer
  • HR-positive, HER2-negative Advanced Breast Cancer
  • HER2-positive Advanced Breast Cancer

Eligibility

Eligible Ages
Over 18 Years
Eligible Sex
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 (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

Study Design

Phase
Phase 1
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
BBO-10203 		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.
  • Drug: BBO-10203
    Participants will receive assigned dose of BBO-10203 orally once daily
  • Drug: Trastuzumab
    Participants will receive trastuzumab as infusion or subcutaneous injection every 21 days
Experimental
BBO-10203 + Trastuzumab 		Participants enrolled in this cohort will receive BBO-10203 tablets orally in combination with trastuzumab (8mg/kg infusion over 90 minutes on Cycle 1 Day 1, 6mg/kg infusion over 30-90 minutes during subsequent cycles or 600mg subcutaneous). This cohort will enroll patients with HER2-positive advanced breast cancer.
  • Drug: BBO-10203
    Participants will receive assigned dose of BBO-10203 orally once daily
  • Drug: Trastuzumab
    Participants will receive trastuzumab as infusion or subcutaneous injection every 21 days
Experimental
BBO-10203 + Fulvestrant 		Participants enrolled in this cohort will receive BBO-10203 tablets orally in combination with fulvestrant (500mg IM). This cohort will enroll patients with HR-positive, HER2-negative advanced breast cancer.
  • Drug: BBO-10203
    Participants will receive assigned dose of BBO-10203 orally once daily
  • Drug: Fulvestrant
    Patients will receive Fulvestrant as an intramuscular injection every 28 days (additional dose on C1D15)
  • Drug: Ribociclib
    Patients will receive Ribociclib orally once a day (21 days on treatment, 7 days off)
Experimental
BBO10203 + Fulvestrant + Ribociclib 		Participants enrolled in this cohort will receive BBO-10203 tablets orally in combination with fulvestrant (500mg IM) and ribociclib (600mg orally) as determined in the dose escalation. This cohort will enroll patients with HR-positive, HER2-negative advanced breast cancer.
  • Drug: BBO-10203
    Participants will receive assigned dose of BBO-10203 orally once daily
  • Drug: Fulvestrant
    Patients will receive Fulvestrant as an intramuscular injection every 28 days (additional dose on C1D15)
  • Drug: Ribociclib
    Patients will receive Ribociclib orally once a day (21 days on treatment, 7 days off)
Experimental
BBO10203 + FOLFOX + Bevacizumab 		Participants enrolled in this cohort will receive BBO-10203 tablets orally in combination with FOLFOX (oxaliplatin 85 mg/m2, leucovorin 400 mg/m2, 5FU 400 mg/m2 + 2400 mg/m2) and bevacizumab (5 mg/kg IV). This cohort will enroll patients with KRAS-mutant advanced colorectal cancer.
  • Drug: BBO-10203
    Participants will receive assigned dose of BBO-10203 orally once daily
  • Drug: FOLFOX
    Patients will receive FOLFOX as infusion every 14 days
  • Drug: Bevacizumab
    Patients will receive bevacizumab as infusion every 28 days

Recruiting Locations

Massachusetts General Hospital
Boston, Massachusetts 02114

More Details

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

Study Contact

BBOT (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, 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.