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

NCT04209465 | Terminated Phase 1 Results FDA Drug

• 1 other identifier: BDTX-189-01
• Study Type: interventional
• Target: 91
• Locations: 4 countries
• Sites: 38

Brief Summary

This was a clinical study with an orally administered drug, BDTX-189 in participants with advanced solid tumors that had 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 were 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 preliminary antitumor activity of BDTX-189 in participants with select allosteric ErbB gene mutations

Conditions

Solid Tumor

Keywords

solid tumor; HER2 mutation; exon 20 insertion mutation; HER2 positive; Genes, HER2; Genes, erbb2; HER2 amplification; HER2 overexpression; genes, exon 20 insertion; lung cancer; non-small cell lung cancer; breast cancer; colon cancer; colorectal cancer; bladder cancer; endometrial cancer; gastric cancer; biliary tract cancer

Outcome Measures

Primary Outcomes (1)

• Number of Dose Limiting Toxicities as a Determinant of the Recommended Phase 2 Dose (RP2D)

  Certain toxicities will be considered dose-limiting unless clearly attributable to an extraneous cause, such as underlying disease.

  After the first dose of treatment for up to 21 days.

Secondary Outcomes (4)

• Phase 1: Incidence of Treatment-emergent Adverse Events as a Measure of Safety and Tolerability of BDTX-189

  From Cycle 1 Day 1 (each cycle is 21 days) until 30 days post last dose

• Phase 1: Plasma Concentration of BDTX-189 as a Measure of Pharmacokinetics

  Multiple time points during Cycles 1-4 (each cycle is 21 days)

• Phase 1: Objective Response Rate as a Preliminary Measure of Antitumor Activity

  Assessed until disease progression or death for up to 12 months

• Phase 1: Progression-free Survival as a Measure of Antitumor Activity

  Assessed until disease progression or death for up to 12 months

Study Arms (1)

Phase 1 - Dose escalation

EXPERIMENTAL

In Part A, cohorts of patients with select HER2, HER3, or EGFR alterations received increasing doses of BDTX-189.

Drug: BDTX-189

Interventions

BDTX-189 DRUG

Participants received a daily, oral dose of BDTX-189 as part of a 3 week cycle.

Phase 1 - Dose escalation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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:

Sponsors & Collaborators

• Black Diamond Therapeutics, Inc.: lead

Study Sites (38)

9250

Scottsdale, Arizona, 85258, United States

Location

9405

Long Beach, California, 90813, United States

Location

9474

Orange, California, 92868, United States

Location

7141

New Haven, Connecticut, 06520, United States

Location

4080

Lake Mary, Florida, 32746, United States

Location

4100

Orlando, Florida, 32827, United States

Location

9535

Plantation, Florida, 33322, United States

Location

4060

Sarasota, Florida, 34232, United States

Location

9035

Atlanta, Georgia, 30322, United States

Location

9530

Rolling Meadows, Illinois, 60008, United States

Location

9092

New Orleans, Louisiana, 70112, United States

Location

9203

Boston, Massachusetts, 02215, United States

Location

9209

Buffalo, New York, 14263, United States

Location

9215

New York, New York, 10016, United States

Location

9236

New York, New York, 10065, United States

Location

9264

Portland, Oregon, 97213, United States

Location

7122

Pittsburgh, Pennsylvania, 15232, United States

Location

4107

Chattanooga, Tennessee, 37404, United States

Location

3000

Nashville, Tennessee, 37203, United States

Location

9003

Dallas, Texas, 75390, United States

Location

9117

Houston, Texas, 77030, United States

Location

9538

Webster, Texas, 77598, United States

Location

9112

Fairfax, Virginia, 22031, United States

Location

9173

Milwaukee, Wisconsin, 53226, United States

Location

9500

Copenhagen, Denmark

Location

9501

Bordeau, 33000, France

Location

9525

Lille, 59000, France

Location

9373

Lyon, 69008, France

Location

9512

Poitiers, 86021, France

Location

9476

Rennes, 44229, France

Location

9496

Barcelona, 08028, Spain

Location

9363

Barcelona, 08035, Spain

Location

9508

Barcelona, 08036, Spain

Location

9429

Madrid, 28007, Spain

Location

9495

Madrid, 28040, Spain

Location

9383

Madrid, 28041, Spain

Location

9382

Madrid, 28050, Spain

Location

9510

Valencia, 46010, Spain

Location

Related Publications (1)

• Erika Paige Hamilton, Manish R. Patel, Jordi Rodon, David S. Hong, Alison M. Schram, Pasi A. Janne, Patricia LoRusso, Jasgit C. Sachdev, Sai Hong Ou, Elizabeth A Buck, Matthew O'Connor, Nigel Waters, Karsten Witt, Carl Cook. Masterkey-01: Phase I/II, open-label multicenter study to assess safety, tolerability, pharmacokinetics, and antitumor activity of BDTX-189, an inhibitor of allosteric ErbB mutations, in patients with advanced solid malignancies. J Clin Oncol 38: 2020 (suppl; abstr TPS3665)

  BACKGROUND

MeSH Terms

Conditions

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Breast Neoplasms; Colonic Neoplasms; Colorectal Neoplasms; Urinary Bladder Neoplasms; Endometrial Neoplasms; Stomach Neoplasms; Biliary Tract Neoplasms

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Urologic Neoplasms; Urogenital Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases; Uterine Neoplasms; Genital Neoplasms, Female; Uterine Diseases; Genital Diseases, Female; Genital Diseases; Stomach Diseases; Biliary Tract Diseases

Limitations and Caveats

Study terminated early. Phase 2 was not conducted. Limited data collection was performed for this study.

Results Point of Contact

• Title: Medical Monitor
• Organization: Black Diamond Therapeutics, Inc.

ClinicalTrials@bdtx.com

617-401-8444

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 19, 2019
• First Posted: December 24, 2019
• Study Start: December 19, 2019
• Primary Completion: September 2, 2022
• Study Completion: September 16, 2022
• Last Updated: April 17, 2025
• Results First Posted: April 17, 2025

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (24); FR (5); DK (1); ES (8)