NCT04209465

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

• Status: Terminated
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 91 (actual)
• Sponsor: Black Diamond Therapeutics, Inc. · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Solid Tumor

Interventions

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

Timeline

• Start date: 2019-12-19
• Primary completion: 2022-09-02
• Completion: 2022-09-16
• First posted: 2019-12-24
• Last updated: 2025-04-17
• Results posted: 2025-04-17

Locations

38 sites across 4 countries: United States, Denmark, France, Spain

Regulatory

• FDA-regulated drug study