This is a clinical study with an orally administered drug, BDTX-189 in participants with advanced solid tumors that have select mutations or alterations in human epidermal growth factor receptor 2 (HER2/ErbB2) genes or epidermal growth factor receptor (EGFR/ErbB1). The main goals of this study are to: - Find the recommended dose of BDTX-189 that can be given safely to participants - Learn more about the side effects of BDTX-189 - Learn what the body does to BDTX-189 after it has been taken (pharmacokinetics or PK) - Determine the antitumor activity of BDTX-189 in participants with select allosteric ErbB gene mutations

NCT04209465

Conditions

1. Solid Tumor

Interventions

1. Drug: BDTX-189

Evidence of second- or third-degree atrioventricular block 2. Clinically significant arrhythmia (as determined by the Investigator) 3. QTcF interval of >470 msec - Leptomeningeal or untreated and/or symptomatic CNS malignancies (primary or metastatic) - Women who are pregnant or breast-feeding - Taking or unable to discontinue proton pump inhibitors within 1 week prior to baseline - Known concurrent KRAS mutation - Known tumor-harboring resistance mutations including EGFR T790M or C797S mutations or HER2 C805S mutation Phase 2 Only: - Prior documented treatment response to approved or investigational HER2 or EGFR tyrosine kinase inhibitor therapies Main Inclusion Criteria: - Histologically- or cytologically-confirmed locally advanced or metastatic solid tumor with documented recurrence or disease progression from standard anticancer therapy in the advanced/metastatic setting - No standard therapy available or standard therapy is considered unsuitable or intolerable according to the Investigator and consultation with the Medical Monitor Phase 1 Only: - Solid tumor patients with alterations that may be associated with antitumor activity based on preclinical data for BDTX-189 such as: 1. Allosteric HER2 or HER3 mutation(s) 2. EGFR or HER2 exon 20 insertion mutation(s) 3. HER2 amplified or overexpressing tumors 4. EGFR exon 19 deletion or L858R mutation Phase 2 Only: - Patients with a solid tumor harboring an: 1. Allosteric HER2 mutation (including but not limited to S310F/Y, R678Q, L755S/P, V777L, V842I) 2. EGFR or HER2 exon 20 insertion mutation Eligible mutations must be determined by a validated next-generation sequencing (NGS) test routinely used by each institution and performed in a CLIA-certified or equivalent laboratory. --- T790M --- --- C797S --- --- C805S ---

Evidence of second- or third-degree atrioventricular block 2. Clinically significant arrhythmia (as determined by the Investigator) 3. QTcF interval of >470 msec - Leptomeningeal or untreated and/or symptomatic CNS malignancies (primary or metastatic) - Women who are pregnant or breast-feeding - Taking or unable to discontinue proton pump inhibitors within 1 week prior to baseline - Known concurrent KRAS mutation - Known tumor-harboring resistance mutations including EGFR T790M or C797S mutations or HER2 C805S mutation Phase 2 Only: - Prior documented treatment response to approved or investigational HER2 or EGFR tyrosine kinase inhibitor therapies Solid Tumor BDTX-189 is an irreversible, small molecular inhibitor that is highly selective versus wild-type EGFR and potent for cancer driver mutations of the ErbB family, including extracellular, transmembrane, and kinase domain allosteric mutations of HER2, as well as EGFR and HER2 exon 20 insertion mutations. --- T790M --- --- C797S --- --- C805S ---