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

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

INTRODUCTION

  • Org Study ID: BDTX-189-01
  • Secondary ID: N/A
  • NTC ID: NCT04209465
  • Sponsor: Black Diamond Therapeutics, Inc.

BRIEF SUMMARY


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

DETAILED DESCRIPTION


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. These allosteric ErbB mutations are found in 1 - 2 % of
most solid tumors and enriched in some cancers with a prevalence of about 2 - 7% such as in
non-small cell lung cancer, breast cancer, colorectal cancer, bladder cancer, and endometrial
cancer. Currently approved HER2 and EGFR directed therapies are not active against the
spectrum of allosteric mutations at relevant and tolerated exposure levels.

This Phase 1/2 multi-center, open-label trial is a first-in-human study that will evaluate
BDTX-189 orally administered daily as a single agent in patients with solid tumors harboring
select mutations or alterations. The Phase 1 portion is a dose escalation primarily designed
to assess the safety and tolerability of BDTX-189 and to determine a recommended Phase 2 dose
(RP2D). Phase 1 will focus on patients with a solid tumor with alterations 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

Following selection of the RP2D, a Phase 2 portion will be initiated to further evaluate the
clinical activity of BDTX-189. Phase 2 will focus on 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.


  • Overall Status
    Recruiting
  • Start Date
    December 19, 2019
  • Phase
    Phase 1/Phase 2
  • Study Type
    Interventional

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

  • Solid Tumor

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: N/A

Maximum Age: 18 Years

Healthy Volunteers: No

OFFICIAL INFORMATION

Name: Carl Cook

Role: Study Director

Affiliation: Black Diamond Therapeutics, Inc.

Overall Contact

Name: Carl Cook

Phone: 1-302-743-7938

Email: ccook@bdtx.com

LOCATION

Facility Status Contact
Facility: 9250
Scottsdale, Arizona 85258
United States
Status: Recruiting Contact: N/A
Facility: 9405
Long Beach, California 90813
United States
Status: Recruiting Contact: N/A
Facility: 9474
Orange, California 92868
United States
Status: Recruiting Contact: N/A
Facility: 7141
New Haven, Connecticut 06520
United States
Status: Recruiting Contact: N/A
Facility: 4080
Lake Mary, Florida 32746
United States
Status: Recruiting Contact: N/A
Facility: 4060
Sarasota, Florida 34232
United States
Status: Recruiting Contact: N/A
Facility: 9035
Atlanta, Georgia 30322
United States
Status: Recruiting Contact: N/A
Facility: 9203
Boston, Massachusetts 02215
United States
Status: Recruiting Contact: N/A
Facility: 9209
Buffalo, New York 14263
United States
Status: Recruiting Contact: N/A
Facility: 9236
New York, New York 10065
United States
Status: Recruiting Contact: N/A
Facility: 7122
Pittsburgh, Pennsylvania 15232
United States
Status: Recruiting Contact: N/A
Facility: 3000
Nashville, Tennessee 37203
United States
Status: Recruiting Contact: N/A
Facility: 9117
Houston, Texas 77030
United States
Status: Recruiting Contact: N/A