rKey-01: A Phase 1/2, Open-label, Two-part, Multicenter Study to Assess the Safety, Tolerability, Pharmacokinetics, and Antitumor Activity of BDTX-189, an Inhibitor of Allosteric ErbB Mutations, in Patients with Advanced Solid Malignancies

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

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