Avenzo's CDK2 Inhibitor AVZO-021 Shows Promising Activity in Breast and Ovarian Cancer Patients
Key Insights
Avenzo Therapeutics (search) reported initial Phase 1 data for AVZO-021, a selective CDK2 (search) inhibitor, showing confirmed responses in patients with HR+/HER2- breast cancer (search) and CCNE1-amplified ovarian cancer (search).
The drug demonstrated a favorable safety profile with relatively low incidence of gastrointestinal and hematologic adverse events compared to other CDK inhibitors.
AVZO-021 showed activity both as monotherapy and in combination with fulvestrant, with all responders remaining on treatment and two patients continuing for over 48 weeks.
Avenzo Therapeutics (search) presented encouraging initial clinical data from its Phase 1/2 study of AVZO-021, a selective cyclin-dependent kinase 2 (CDK2 (search)) inhibitor, at the 2025 San Antonio Breast Cancer Symposium. The data demonstrated preliminary clinical activity across patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) breast cancer and cyclin E1 (search) (CCNE1)-amplified ovarian cancer, with a generally well-tolerated safety profile.
Clinical Activity Across Multiple Tumor Types
The study evaluated 35 patients with advanced solid tumors (search) treated with AVZO-021 monotherapy across nine dose levels, and 10 patients with HR+/HER2- breast cancer (search) treated with AVZO-021 in combination with fulvestrant. The patient population was heavily pretreated, with a median of 3.0 prior therapies in the metastatic setting (range zero to 11), and all breast cancer patients had received at least one prior CDK4 (search)/6 inhibitor.
Among 19 efficacy-evaluable patients treated with AVZO-021 monotherapy, three patients experienced confirmed responses, including two with HR+/HER2- breast cancer (search) with onset at weeks 15 and 36, and one with CCNE1-amplified ovarian cancer (search) with onset at week 35. Additionally, seven patients achieved stable disease, including six with HR+/HER2- breast cancer who remain on treatment.
In the combination cohort, one of nine efficacy-evaluable HR+/HER2- breast cancer (search) patients experienced a confirmed response with onset at week 7, with the confirmatory scan obtained after the data cut-off date. Three patients in this group achieved stable disease and remain on treatment.
Favorable Safety Profile
The safety analysis included 45 patients, comprising 35 patients treated with AVZO-021 monotherapy at doses ranging from 20 mg once daily to 250 mg once daily, and 10 patients treated with the combination. All-grade treatment emergent adverse events reported in greater than 20 percent of patients were nausea (44%), fatigue (38%), anemia (33%), and vomiting (29%).
Importantly, the majority of adverse events were Grade 1 or Grade 2, and no patients discontinued treatment due to adverse events. This represents a potentially improved tolerability profile compared to other CDK inhibitors, which commonly cause more severe gastrointestinal and hematologic toxicities.
Pharmacokinetic and Biomarker Data
Pharmacokinetic data indicated that continuous CDK2 (search) target coverage was achieved at doses of 90 mg once daily and above. The study also demonstrated comparable exposures of AVZO-021 between monotherapy and combination with fulvestrant at 150 mg once daily, indicating no drug-drug interaction. Additionally, significant decreases in circulating tumor DNA (ctDNA) were observed, suggesting biological activity.
Clinical Significance and Future Development
"CDK2 (search) has emerged as an important resistance mechanism in patients with HR+/HER2- breast cancer (search), especially for patients who progress on CDK4 (search)/6 inhibitors," said Alberto J. Montero, M.D., MBA, Clinical Director, Breast Cancer Medical Oncology Program and Diana Hyland Endowed Chair for Breast Cancer at University Hospitals Seidman Cancer Center, Case Western Reserve University. "These data reported today for AVZO-021 are exciting as they not only demonstrate the activity and tolerability of AVZO-021, but the potential for its use in combination with other agents."
All responders remain on treatment, with two patients continuing for greater than 48 weeks, suggesting durable responses. Mohammad Hirmand, M.D., Co-founder and Chief Medical Officer of Avenzo Therapeutics (search), noted the company's plans to advance AVZO-021 development in combination with AVZO-023 (search), their highly potent and selective CDK4 (search) inhibitor.
The company also presented the study design for an ongoing Phase 1/2 study evaluating AVZO-023 (search) as a single agent and in combination with AVZO-021 and/or endocrine therapy, indicating a comprehensive approach to targeting cell cycle regulation in cancer treatment.