Investigational Drug
AVZO-021
HealthScout AI Analysis
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Overview
AVZO-021 (formerly ARTS-021) is an orally bioavailable, highly selective cyclin-dependent kinase 2 (CDK2) inhibitor being developed for cancers with CDK2 dependence, including HR+/HER2− metastatic breast cancer and CCNE1-amplified solid tumors. A first‑in‑human, open‑label Phase 1/2 study (NCT05867251) is ongoing in the United States (multiple centers, including Yale) and Australia. As of October 7, 2025, no human efficacy or safety outcomes have been publicly reported. (ascopubs.org)
Mechanism of action
- Target: CDK2, a key kinase driving the G1/S cell-cycle transition via Cyclin E/CDK2 and implicated in resistance to CDK4/6 inhibitors and in tumors with CCNE1 amplification. (aacrjournals.org)
- Preclinical profile: Sub‑nanomolar inhibition of CDK2/Cyclin E1 with high selectivity over other CDKs; broad kinome selectivity (low S10 hit rate). Demonstrated anti‑tumor activity in CCNE1‑amplified xenograft models and enhanced activity when combined with palbociclib in ER+ breast cancer models. Additional preclinical work suggests apoptotic activity in small‑cell lung cancer models and synergy with BCL‑2/BCL‑xL inhibition. (aacrjournals.org)
Clinical development
- Trial design: Phase 1/2, dose‑escalation/expansion evaluating AVZO‑021 as monotherapy in CCNE1‑amplified solid tumors, and in combinations for (a) ER+/HER2− breast cancer with endocrine therapy plus a CDK4/6 inhibitor, (b) CCNE1‑amplified ovarian cancer with carboplatin. First patient was dosed in October 2023; the study remains ongoing. (ascopubs.org)
- Planned combinations: Endocrine therapy plus CDK4/6 inhibitors; carboplatin; and a separate collaboration to evaluate AVZO‑021 with sacituzumab govitecan (Trodelvy) in HR+/HER2− metastatic breast cancer within the ongoing Phase 1/2 program. (ascopubs.org)
- Sponsorship/licensing: Originally developed by Allorion Therapeutics (as ARTS‑021); licensed globally (ex‑Greater China) to Avenzo Therapeutics in January 2024. (avenzotx.com)
Efficacy
- Human data: No response rates or other clinical efficacy outcomes have been disclosed as of October 7, 2025. The ASCO 2023 abstract describes the trial rationale and design, noting the study is ongoing. (ascopubs.org)
- Preclinical signals: Tumor stasis/regressions in CCNE1‑altered models and enhanced activity with CDK4/6 or KRAS G12C inhibition in xenografts were reported in conference abstracts. These findings support the combination strategies under clinical evaluation. (aacrjournals.org)
Safety
- Human data: No aggregate safety findings have been reported publicly to date. The ongoing first‑in‑human study is designed to characterize safety, tolerability, pharmacokinetics, and pharmacodynamics. (ascopubs.org)
Further reading
- AACR 2022 preclinical abstract detailing potency/selectivity and activity in CCNE1‑amplified models: https://aacrjournals.org/cancerres/article/82/12_Supplement/2568/704249/Abstract-2568-ARTS-021-is-a-potent-and-selective (aacrjournals.org)
- ASCO 2023 trial-in-progress abstract (Phase 1/2 design): https://ascopubs.org/doi/abs/10.1200/JCO.2023.41.16_suppl.e17546 (ascopubs.org)
- Allorion press release (first patient dosed; NCT05867251): https://www.prnewswire.com/news-releases/allorion-therapeutics-announces-first-patient-dosed-in-phase-12-study-of-arts-021-a-potential-best-in-class-cdk2-inhibitor-for-advanced-or-metastatic-solid-tumors-301954292.html (prnewswire.com)
- Avenzo press release (global license to AVZO‑021): https://avenzotx.com/press-releases/avenzo-therapeutics-announces-global-license-of-avzo-021-arts-021-a-potentially-best-in-class-clinical-stage-cdk2-inhibitor-from-allorion-therapeutics/ (avenzotx.com)
- Avenzo–Gilead collaboration (AVZO‑021 + Trodelvy in HR+/HER2− MBC): https://avenzotx.com/press-releases/avenzo-therapeutics-announces-clinical-study-collaboration-with-gilead-sciences-to-evaluate-avzo-021-and-trodelvy-in-hr-her2-metastatic-breast-cancer/ (avenzotx.com)
- Yale Medicine trial listing (site information/contacts): https://www.yalemedicine.org/clinical-trials/study-of-arts-021-in-patients-with-advanced-solid-tumors (yalemedicine.org)
Note: The above sources indicate the trial is ongoing with no publicly available human efficacy or safety results as of October 7, 2025.
Last updated: Oct 2025
Active trials using AVZO-021
Found 2 active trials using this drug:
HealthScout AI summary: Adults with advanced solid tumors (dose escalation enriched for CDK4/CCND1-amplified tumors) and a phase 2 focus on HR+/HER2- metastatic breast cancer receive AVZO-023, an oral selective CDK4 inhibitor, as monotherapy or combined with AVZO-021 (selective CDK2 inhibitor) and/or endocrine therapy (fulvestrant or letrozole). Prior CDK2/4/6 inhibitor exposure is excluded; endpoints assess safety, PK/PD, and antitumor activity with combination cohorts at RP2D in HR+/HER2- disease.
ClinicalTrials.gov ID: NCT06998407
HealthScout AI summary: This trial enrolls adults with advanced or metastatic solid tumors, specifically HR+/HER2- breast cancer progressed after standard therapy or CCNE1-amplified malignancies (including ovarian, endometrial, TNBC), to receive AVZO-021, an oral selective CDK2 inhibitor targeting cell cycle dysregulation, as monotherapy or in combination with standard agents. Patients must have measurable disease, ECOG 0–1, and no prior CDK2 inhibitor exposure.
ClinicalTrials.gov ID: NCT05867251
