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

Status
Closed
Cancer Type
Solid Tumor
Unknown Primary
Trial Phase
Phase I
Phase II
Eligibility
18 Years and older, Male and Female
Study Type
Treatment
NCT ID
NCT04209465
Protocol IDs
BDTX-189-01 (primary)
NCI-2020-02246
Study Sponsor
Black Diamond Therapeutics, Inc.

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

Objectives

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.

Eligibility

  1. 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
  2. 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:
  3. Solid tumor patients with alterations that may be associated with antitumor activity based on preclinical data for BDTX-189 such as:
  4. Allosteric HER2 or HER3 mutation(s)
  5. EGFR or HER2 exon 20 insertion mutation(s)
  6. HER2 amplified or overexpressing tumors
  7. EGFR exon 19 deletion or L858R mutation Phase 2 Only:
  8. Patients with a solid tumor harboring an:
  9. Allosteric HER2 mutation (including but not limited to S310F/Y, R678Q, L755S/P, V777L, V842I)
  10. 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.
  11. Adequate archival tumor tissue or willing to undergo pretreatment biopsy
  12. Measurable disease according to RECIST version 1.1
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