On April 28, 2026 Avenzo Therapeutics, Inc. ("Avenzo"), a clinical-stage biotechnology company developing next-generation oncology therapies, reported initiation of the combination cohort evaluating AVZO-023, its potential best-in-class cyclin-dependent kinase 4 (CDK4) selective inhibitor, in combination with AVZO-021, its potential best-in-class cyclin-dependent kinase 2 (CDK2) selective inhibitor, with fulvestrant in patients with advanced or metastatic hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) breast cancer in the ongoing Phase 1 portion of the ORION-1 Phase 1/2 clinical study.
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"Hyperactivation of CDK2 has emerged as a key resistance mechanism to CDK4/6 inhibitors, and we believe addressing both CDK4 and CDK2 with selective inhibitors represents a rational approach to improving outcomes for patients with HR+/HER2- breast cancer," said Antonio Giordano, M.D., Ph.D., Clinical Director, Center for Cancer Therapeutic Innovation, Dana-Farber Cancer Institute. "The combination of AVZO-023 and AVZO-021 is designed to optimize CDK4 target coverage while simultaneously targeting CDK2-driven resistance, and the selective profiles of both agents may enable a tolerability advantage over less selective approaches."
The Phase 1/2 first-in-human, open-label ORION-1 clinical study is designed to assess the safety, tolerability, and preliminary clinical activity of AVZO-023 with endocrine therapy as well as the combination of AVZO-023 and AVZO-021 with endocrine therapy. The combination cohort will evaluate AVZO-023 and AVZO-021 with fulvestrant in patients with HR+/HER2- metastatic breast cancer. AVZO-021 is currently being studied in a separate Phase 1/2 clinical study in HR+/HER2- metastatic breast cancer and other advanced solid tumors, and the company plans to present updated safety and efficacy results from the Phase 1 portion of the ongoing study at the 2026 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting.
"We are encouraged by the early emerging data from AVZO-023 and believe the combination of our potential best-in-class CDK4 and CDK2 selective inhibitors has the potential to meaningfully improve outcomes for patients with HR+/HER2- breast cancer," said Mohammad Hirmand, M.D., Co-founder, and Chief Medical Officer of Avenzo Therapeutics. "We look forward to advancing this program and exploring the full potential of this novel combination."
(Press release, Avenzo Therapeutics, APR 28, 2026, View Source [SID1234664849])