Clinical Trial 23585

• Overview

  Study Title:

  A Phase 1a/1b Open-Label Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Efficacy of BBO-10203 in Subjects with Advanced Solid Tumors (The BREAKER-101 Trial)

  Objective:

  Phase 1a Dose Escalation: BBO-10203 Monotherapy *Primary - To evaluate the safety and tolerability of BBO-10203, an inhibitor of the PI3Kα:RAS interaction, in subjects with locally advanced unresectable or metastatic (ie, advanced) HER2-positive BC; HR-positive, HER2-negative BC; KRAS mutant NSCLC; and KRAS mutant CRC. *Secondary - To evaluate preliminary antitumor activity of BBO-10203. - To characterize the PK of BBO-10203. Phase 1a Dose Escalation: BBO-10203 + Trastuzumab in Subjects with HER2-positive aBC; BBO-10203 + Fulvestrant +/- Ribociclib in Subjects with HR-positive HER2-negative aBC; BBO-10203 + FOLFOX + Bevacizumab in Subjects with KRAS mutant aCRC *Primary - To determine the recommended dose of BBO-10203 to be administered in combination with: Trastuzumab in subjects with HER2-positive aBC Fulvestrant +/- ribociclib in subjects with HR-positive HER2-negative aBC FOLFOX + bevacizumab in subjects with KRAS mutant aCRC in Phase 1b Dose Expansion by evaluation of totality of safety, PK, and efficacy data. *Secondary - To evaluate preliminary antitumor activity of BBO-10203 in combination with: Trastuzumab in subjects with HER2-positive aBC Fulvestrant +/- ribociclib in subjects with HR-positive HER2-negative aBC FOLFOX + bevacizumab in subjects with KRAS mutant aCRC All Cohorts: *Exploratory - To characterize circulating and/or intratumoral pharmacodynamic (PD) activity of BBO-10203 and biomarkers that may correlate with response. - To characterize metabolites of BBO-10203 in plasma.

• Treatments

  Therapies:

  CDK4/6 Inhibitor; Chemoimmunotherapy; Hormonal Therapy; Immunotherapy; PI3K Alpha RAS inhibitor

  Medications:

  Avastin (Bevacizumab); BBO-10203 (); Bevacizumab (); FOLFOX (); Faslodex (fulvestrant); Herceptin (Trastuzumab); LEE011 (Ribociclib); Ribociclib (); Trastuzumab (); fulvestrant (); rhuMAb HER2 (Trastuzumab)

• Inclusion Criteria

  Key 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
  • Additional criteria may apply

• Exclusion Criteria

  Key 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
  • Additional criteria may apply

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