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

PRIMARY OUTCOMES

Primary Outcome 1 - Measure: Incidence of dose limiting toxicities as a determinant of the Recommended Phase 2 Dose (RP2D)

Primary Outcome 1 - Timeframe: After the first dose of treatment for up to 21 days.

Primary Outcome 2 - Measure: Phase 2: Objective response rate as a measure of antitumor activity

Primary Outcome 2 - Timeframe: Assessed until disease progression or death for up to 12 months

CONDITION

• S

ELIGIBILITY

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.
* 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:
1. Serum creatinine ≥1.5 × upper limit of normal (ULN) or calculated creatinine clearance ≤60 mL/min using Cockcroft-Gault equation

- 2. Total bilirubin ≥1.5 × ULN or ≥3.0 × ULN in the presence of documented Gilbert's syndrome

- 3. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≥2.5 × ULN, or AST or ALT ≥5.0 × ULN in the presence of liver metastases

- 4. Hematologic function:
1. Absolute neutrophil count (ANC) ≤1000 cells/μL

- 2. Hemoglobin ≤8.5 g/dL or 5.28 mmol/L

- 3. Platelet count ≤75,000/μL

- * Significant cardiovascular disease, including:
1. 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 - 2. Myocardial infarction, severe or unstable angina within 6 months prior to baseline - 3. Significant thrombotic or embolic events within 3 months prior to baseline - 4. History or presence of any uncontrolled cardiovascular disease - 5. Personal or family history of long QT syndrome - * ECG findings meeting any of the following criteria:
1. 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

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

OFFICIAL INFORMATION

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Overall Contact

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LOCATION