Avenzo Therapeutics Advances Dual CDK Inhibitor Breast Cancer Study

SAN DIEGO, Calif., April 28, 2026

Avenzo Therapeutics, Inc. has announced the initiation of the combination cohort in its ongoing Phase 1/2 ORION-1 clinical study, evaluating AVZO-023, a potential best-in-class CDK4 selective inhibitor, in combination with AVZO-021, a potential best-in-class CDK2 selective inhibitor, alongside fulvestrant for patients with advanced or metastatic HR+/HER2- breast cancer. This strategic development reflects Avenzo’s commitment to advancing next-generation targeted oncology therapies designed to overcome treatment resistance and improve patient outcomes in hormone receptor-positive breast cancer.

Targeting CDK4 and CDK2 to Overcome Resistance

The combination of AVZO-023 and AVZO-021 is based on a strong scientific rationale addressing one of the major challenges in HR+/HER2- metastatic breast cancer treatment: resistance to CDK4/6 inhibitors. Research has shown that CDK2 hyperactivation is a key mechanism driving resistance in patients receiving standard CDK4/6 therapies. By selectively targeting both CDK4 and CDK2, Avenzo aims to improve therapeutic response while maintaining better tolerability compared to broader, less selective inhibition strategies.

AVZO-023 is designed to optimize CDK4 target coverage, while AVZO-021 specifically targets CDK2-driven resistance pathways, creating a potentially synergistic treatment approach. According to leading oncology experts, this dual inhibition strategy may offer a significant clinical advantage in extending disease control and delaying progression in metastatic breast cancer patients who face limited options after resistance develops.

ORION-1 Phase 1/2 Study Expands Combination Strategy

The ongoing ORION-1 first-in-human, open-label Phase 1/2 study is designed to evaluate the safety, tolerability, pharmacology, and preliminary clinical activity of AVZO-023 both as a single agent and in combination with endocrine therapy. The newly initiated combination cohort specifically focuses on AVZO-023 + AVZO-021 + fulvestrant, targeting patients with advanced HR+/HER2- metastatic breast cancer, one of the largest and most commercially significant oncology markets globally.

At the same time, AVZO-021 is being evaluated separately in another Phase 1/2 study for advanced solid tumors and HR+/HER2- breast cancer combinations. Avenzo also plans to present updated Phase 1 safety and efficacy data from the AVZO-021 program at the upcoming 2026 ASCO Annual Meeting, further strengthening investor and clinical interest in its oncology pipeline.

Expanding a Next-Generation Oncology Pipeline

Avenzo Therapeutics continues to build a strong oncology platform with a pipeline that includes both small molecule inhibitors and antibody-drug conjugates (ADCs). In addition to AVZO-021 and AVZO-023, the company is advancing AVZO-1418, a potential best-in-class EGFR/HER3 bispecific ADC, and AVZO-103, a Nectin4/TROP2 bispecific ADC, both currently in Phase 1/2 studies for advanced solid tumors.

This diversified strategy positions Avenzo as an emerging leader in precision oncology, with multiple opportunities across breast cancer and broader solid tumor indications. The company’s focus on selective inhibition and novel combination therapies reflects the growing industry demand for more personalized, better-tolerated cancer treatments.

As the ORION-1 study progresses, the dual CDK4/CDK2 inhibition approach may represent a significant breakthrough in managing HR+/HER2- metastatic breast cancer, offering hope for longer-lasting responses and improved quality of life for patients facing advanced disease.

Source: Avenzo Therapeutics press release