A Study of BDTX-189, an Orally Available Allosteric ErbB Inhibitor, in Patients With Advanced Solid Tumors.

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:

Allosteric HER2 or HER3 mutation(s)
EGFR or HER2 exon 20 insertion mutation(s)
HER2 amplified or overexpressing tumors
EGFR exon 19 deletion or L858R mutation

Phase 2 Only:

Patients with a solid tumor harboring an:

Allosteric HER2 mutation (including but not limited to S310F/Y, R678Q, L755S/P, V777L, V842I)
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.

Adequate archival tumor tissue or willing to undergo pretreatment biopsy
Measurable disease according to RECIST version 1.1

Main Exclusion Criteria:

Clinical laboratory values meeting the following criteria within 4 weeks (28 days) prior to baseline:

Serum creatinine ≥1.5 × upper limit of normal (ULN) or calculated creatinine clearance ≤60 mL/min using Cockcroft-Gault equation
Total bilirubin ≥1.5 × ULN or ≥3.0 × ULN in the presence of documented Gilbert's syndrome
Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≥2.5 × ULN, or AST or ALT ≥5.0 × ULN in the presence of liver metastases

Hematologic function:

Absolute neutrophil count (ANC) ≤1000 cells/μL
Hemoglobin ≤8.5 g/dL or 5.28 mmol/L
Platelet count ≤75,000/μL

Significant cardiovascular disease, including:

Cardiac failure New York Heart Association Class III or IV, or left ventricular ejection fraction (LVEF) <50% or below the lower limit of the Institution's normal range
Myocardial infarction, severe or unstable angina within 6 months prior to baseline
Significant thrombotic or embolic events within 3 months prior to baseline
History or presence of any uncontrolled cardiovascular disease
Personal or family history of long QT syndrome

ECG findings meeting any of the following criteria:

Evidence of second- or third-degree atrioventricular block
Clinically significant arrhythmia (as determined by the Investigator)
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