A Phase Ia/Ib Open-Label Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Efficacy of BBO-10203 in Subjects With Advanced Solid Tumors (The BREAKER-101 Study)

Study Identifier:
TBBO10203-101
CT.gov Identifier:
NCT06625775
EudraCT Identifier:
202452000000
EU Trial (CTIS) Number:
2024-519445-29-00
Study Contact Information:
N/A
Recruiting

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Study Summary

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

To evaluate BBO-10203 in patients with locally advanced or metastatic HER2+ breast cancer, HR+/HER2- breast cancer, KRAS mutant colorectal cancer, and KRAS mutant non-small cell lung cancer

To evaluate the safety, tolerability, pharmacokinetics, and preliminary antitumor activity of BBO-10203 as monotherapy and in combination with trastuzumab, fulvestrant ± ribociclib, or FOLFOX + bevacizumab in patients with locally advanced or metastatic HER2+ breast cancer, HR+/HER2- breast cancer, KRAS mutant colorectal cancer, and KRAS mutant non-small cell lung cancer.

Key endpoints include safety and tolerability, anti-tumor activity, and pharmacokinetics.

To evaluate the safety, tolerability, and efficacy of BBO-10203 in patients with advanced solid tumors

To evaluate the safety, tolerability, pharmacokinetics, and preliminary antitumor activity of BBO-10203 as monotherapy 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. Dose escalation (or de-escalation) of BBO-10203 monotherapy will initially follow a Bayesian optimal interval (BOIN) design.

Medical Condition
The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.
  • Solid Tumor
  • Breast Cancers
  • Biomarkers
  • Bowel (Colorectal)
  • Metastatic Lung Cancer
  • Other Lung Cancer
  • Breast
    • Phase
    The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
    I
    Sex
    Female & Male
    Age
    18+ years
    Study Drug
  • Drug: 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 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
    • Study Status
    Indicates the current recruitment status or the expanded access status
    Recruiting

    Requirements information
    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
    • Adults with locally advanced and unresectable or metastatic HER2+ aBC, HR+/HER2– advanced breast cancer (aBC), KRAS mutant aCRC, or KRAS mutant aNSCLC; measurable disease per RECIST v1.1 except for HR+/HER2– aBC ; ECOG performance status 0 or 1. ≥2 prior lines of anti-HER2-directed therapy. 1 prior line is acceptable if no other regionally available SoC. 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. Confirmed PIK3CA mutation, must have been treated with a CDK4/6i for at least 6 months. Confirmed PIK3CA mutation, no prior systemic therapy in the aBC setting permitted. One prior line of irinotecan-containing therapy for locally advanced or metastatic CRC is allowed.
    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. Prior Pi3k/AKTi patients are excluded for dose expansion for HR+ BC >1 line of chemotherapy is excluded for HR+ BC Patients with untreated and/or non-stable brain metastases are excluded

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    Study Locations

    Location
    Investigator
    Status
    Condition(s) Treated at Site
    Location
    START Madrid, Spain (FJD)
    Madrid, Spain, 28040
    Investigator
    Victor Moreno Garcia
    Status
    Recruiting
    Condition(s) Treated at Site
    Solid Tumor
    Breast Cancers
    Biomarkers
    Bowel (Colorectal)
    Metastatic Lung Cancer
    Other Lung Cancer
    Breast
    Location
    START Barcelona
    Barcelona, Spain, 08023
    Investigator
    Tatiana Hernandez Guerrero
    Status
    Recruiting
    Condition(s) Treated at Site
    Solid Tumor
    Breast Cancers
    Biomarkers
    Bowel (Colorectal)
    Metastatic Lung Cancer
    Other Lung Cancer
    Breast