Phase 1 Trial of BTX-9341 in HR+/HER2– Breast Cancer Doses First Patient

3D rendered medical illustration of breast cancer: © Sebastian Kaulitzki - stock.adobe.com

A phase 1 trial evaluating BTX-9341, the investigational oral and bifunctional degrader of CDK4/6, as a monotherapy and in combination with fulvestrant has dosed its first patient with advanced and/or metastatic hormone receptor-positive (HR+)/HER2-negative (HER2–) breast cancer who have previously received CDK4/6 inhibitor therapy either in the adjuvant or metastatic setting.¹

"BTX-9341 is a potent and selective CDK4/6 degrader that has shown significant anti-tumor activity in both CDK4/6 inhibitor naive and resistant preclinical models. We are optimistic that it will meet a critical unmet medical need for patients with HR+/HER2– breast cancer who have received prior CDK4/6 inhibitor therapy," said Leah Fung, PhD, chief executive officer of Biotheryx, in a press release. "Dosing the first patient in this trial represents a significant milestone for Biotheryx, the patients we aim to serve, and the scientists who have made this possible."

The phase 1 trial includes a dose-escalation portion where BTX-9341 is being investigated as a monotherapy, followed by in a combination with fulvestrant. Experts will evaluate the safety, tolerability and pharmacokinetic and pharmacodynamic activity of BTX-9341 when given alone and in combination with fulvestrant.

A dose-expansion portion will also be included with BTX-9341 combined with fulvestrant. Once the recommended phase 2 dose of the combination is established in the escalation portion of the study, the expansion cohort will provide a formal evaluation of efficacy.

"We are thrilled to have dosed the first patient with BTX-9341 at The START Center for Cancer Research," stated Amita Patnaik, MD, FRCPC, START co-founder and co-director of clinical research, in the press release. "BTX-9341 is a highly novel, first-in-class, potent and selective degrader of CDK4/6, representing an innovative therapeutic approach. It has the potential to transform the care of patients with advanced and/or metastatic HR+/HER2– breast cancer, particularly those who have received prior CDK4/6 inhibitor therapies. This milestone is perfectly aligned with START's mission to accelerate drug development and provide early access to cutting-edge anticancer therapies, bringing hope to patients and their families."

About BTX-9341

BTX-9341 is a promising first-in-class, oral degrader of CDK4/6 that shows potential in HR+/HER2– breast cancer. Preclinically, BTX-9341 has achieved potent and selective degradation of CDK4/6, leading to robust inhibition of Cyclin E and CDK2 transcription and cell cycle arrest. A key advantage of BTX-9341 is its potential to overcome resistance mechanisms that limit the effectiveness of CDK4/6 inhibitors in the second line for these patients with HR+/HER2– breast cancer.

In additional preclinical models, BTX-9341 administered orally showed in vivo CDK4/6 degradation and demonstrated benefits in antitumor activity when given as a monotherapy vs current standard of care treatments. Synergy with selective estrogen receptor degraders like fulvestrant, elacestrant (Orserdu), and camizestrant (formerly AZD 9833) were also observed with BTX-9341 in CDK4/6 naive and resistant models.

In May 2024, the FDA granted clearance to the investigational new drug application for BTX-9341 in HR+/HER2– breast cancer.²

REFERENCES:

1. Biotheryx announces first patient dosed in phase 1 clinical trial of BTX-9341, a first-in-class, dual bifunctional degrader of CDK4/6, as a monotherapy and in combination with fulvestrant for HR+/HER2- breast cancer. News release. Biotheryx, Inc. July 17, 2024. Accessed July 17, 2024. https://tinyurl.com/46bfafae

2. Biotheryx announces U.S. FDA clearance of investigational new drug application for BTX-9341, a first-in-class, dual bifunctional degrader of CDK4/6. News release. Biotheryx, Inc. May 7, 2024. Accessed July 17, 2024. https://tinyurl.com/2t87wbh6