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NCT04209465 · REGISTRY CONDITION SEARCH

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

Found through the registry condition index, not selected as a treatment recommendation. This discovery collection was restricted to studies with posted results.

Phase
PHASE1
Status at capture
TERMINATED
Registry last update
2025-04-17

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

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

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

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outcome · POSTED

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

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outcome · POSTED

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

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outcome · POSTED

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

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outcome · POSTED

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

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part
eligibility Criteria
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 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
healthy Volunteers
false
minimum Age
18 Years
sex
ALL
std Ages
  1. ADULT
  2. OLDER_ADULT
Treatment arms and interventions
arm Groups
  1. description
    In Part A, cohorts of patients with select HER2, HER3, or EGFR alterations received increasing doses of BDTX-189.
    intervention Names
    1. Drug: BDTX-189
    label
    Phase 1 - Dose escalation
    type
    EXPERIMENTAL
interventions
  1. arm Group Labels
    1. Phase 1 - Dose escalation
    description
    Participants received a daily, oral dose of BDTX-189 as part of a 3 week cycle.
    name
    BDTX-189
    type
    DRUG
Study design
allocation
NA
intervention Model
SEQUENTIAL
masking Info
masking
NONE
primary Purpose
TREATMENT
Enrollment
count
91
type
ACTUAL
Registered outcome plans (not posted results)
primary Outcomes
  1. description
    Certain toxicities will be considered dose-limiting unless clearly attributable to an extraneous cause, such as underlying disease.
    measure
    Number of Dose Limiting Toxicities as a Determinant of the Recommended Phase 2 Dose (RP2D)
    time Frame
    After the first dose of treatment for up to 21 days.
secondary Outcomes
  1. description
    Adverse events will be assessed by National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.
    measure
    Phase 1: Incidence of Treatment-emergent Adverse Events as a Measure of Safety and Tolerability of BDTX-189
    time Frame
    From Cycle 1 Day 1 (each cycle is 21 days) until 30 days post last dose
  2. description
    Blood samples will be taken to measure the plasma concentrations of BDTX-189 in both a fed and fasted state.
    measure
    Phase 1: Plasma Concentration of BDTX-189 as a Measure of Pharmacokinetics
    time Frame
    Multiple time points during Cycles 1-4 (each cycle is 21 days)
  3. description
    Objective response is defined as the proportion of participants who achieved a complete response (CR; disappearance of all target and non-target lesions) or partial response (PR; at least a 30% decrease from baseline in the sum of diameters of target lesions) per RECIST version 1.1.
    measure
    Phase 1: Objective Response Rate as a Preliminary Measure of Antitumor Activity
    time Frame
    Assessed until disease progression or death for up to 12 months
  4. description
    Progression-free survival is the time from first study dose until disease progression (PD; target lesion increase of 20% and at least 5mm from smallest on-study lesion sum, the appearance of new lesions, or unequivocal progression of non-target lesions) per RECIST v1.1.
    measure
    Phase 1: Progression-free Survival as a Measure of Antitumor Activity
    time Frame
    Assessed until disease progression or death for up to 12 months
Full study description
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
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 was a first-in-human study that evaluated BDTX-189 orally administered daily as a single agent in patients with solid tumors harboring select mutations or alterations. The Phase 1 portion was 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 focused on patients with a solid tumor and 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 Eligible mutations must have been determined by a validated next-generation sequencing (NGS) test routinely used by each institution and performed in a CLIA-certified or equivalent laboratory. The Phase 2 portion was not initiated.
Source references
references
  1. citation
    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)
    type
    BACKGROUND
Source notices and limitations
    Discovery and provenance
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    Preserved source evidence · Not medical advice