A Phase 1/2 interventional study of AVZO-021 and Fulvestrant in HR+/HER2- Breast Cancer and HR+, HER2-, Advanced Breast Cancer, sponsored by Avenzo Therapeutics, Inc.. Recruiting at 16 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-08-10.
Sponsored by Avenzo Therapeutics, Inc. · Phase 1/2, Interventional, and Treatment
This study, the first clinical trial of AVZO-023, aims to determine the safety, tolerability, pharmacokinetics (PK), pharmacodynamics, maximum tolerated dose, and anti-tumor effects of AVZO-023 in patients with advanced solid tumors. AVZO-023 is an oral medication that inhibits cyclin-dependent kinase 4 (CDK4).
AVZO-023 is an oral, potent, and selective inhibitor of CDK4. AVZO-021 is an oral, potent, and selective inhibitor of CDK2 that is currently being investigated in a global Phase 1/2 study in patients with advanced hormone receptive positive (HR+)/human epidermal growth factor receptor 2 negative (HER2-) breast cancer (NCT05867251).
In Phase 1, the safety and tolerability of AVZO-023 in patients with HR+/HER2- locally advanced or metastatic breast cancer (mBC) will be assessed. The goal of Phase 1 is to determine the MTD/preliminary RP2D of AVZO-023 for use as monotherapy and in combination with AVZO-021 with or without endocrine therapy (ET).
Phase 2 will assess the antitumor activity and confirm the RP2D of AVZO-023 in combination therapy in patients with HR+/HER2- locally advanced or mBC.
Key Inclusion Criteria:
Key Exclusion Criteria:
Escalating doses of twice daily, oral AVZO-023 in 28-day cycles, with addition of fulvestrant
Drug: Fulvestrant · Drug: AVZO-023
Escalating doses of twice daily, oral AVZO-023 in combination with once daily, oral AVZO-021 in 28-day cycles, with addition of fulvestrant
Drug: AVZO-021 · Drug: Fulvestrant · Drug: AVZO-023
Escalating doses of twice daily, oral AVZO-023 in combination with once daily, oral AVZO-021, with once daily, oral letrozole in 28-day cycles
Drug: AVZO-021 · Drug: Letrozole · Drug: AVZO-023
Oral doses of AVZO-023 in 28-day cycles at the RP2D determined in Part 1B/1C, in combination with: 2A) letrozole 2B) fulvestrant 2C) AVZO-021 plus fulvestrant 2D) AVZO-021 plus letrozole
Drug: AVZO-021 · Drug: Fulvestrant · Drug: Letrozole · Drug: AVZO-023
AVZO-021 is an oral selective CDK2 inhibitor
Antineoplastic agent, estrogen receptor antagonist
Also known as: Faslodex
Antineoplastic agent, aromatase inhibitor
Also known as: Femara
AVZO-023 is an oral selective CDK4 inhibitor
Occurrence of Dose Limiting Toxicities (DLTs) during the first cycle (Phase 1)
Number of participants with DLTs assessed for severity using CTCAE v5.0 criteria will be summarized by dose level.
Time frame: Cycle 1 (28 Days)
Number of Participants with Treatment Emergent Adverse Events (TEAEs) and lab abnormalities (Phase 1)
Time frame: From baseline until end of study treatment or study completion (approximately 2 years)
Determine the Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RP2D) (Phase 1)
Time frame: Approximately 16 months
Objective Response Rate (ORR) (Phase 2)
Defined as the proportion of patients with a confirmed Complete Response (CR) or Partial Response (PR), as determined by the investigator by radiographic disease assessment according to RECIST v1.1.
Time frame: From baseline through disease progression or study completion (approximately 2 years)
Objective Response Rate (ORR) (Phase 1)
Time frame: From baseline through disease progression or study completion (approximately 2 years)
Duration of response (DOR) (Phase 1 and Phase 2)
Defined as the time from the first confirmed response to radiologic/objective progression.
Time frame: From baseline through time to event on study or study completion (approximately 2 years)
Progression Free Survival (PFS) (Phase 1 and Phase 2)
Defined as the time from study drug treatment to death or disease progression, as determined by the investigator by radiographic disease assessment according to RECIST v1.1.
Time frame: From baseline through time to event on study or study completion (approximately 2 years)
Overall Survival (OS) (Phase 1 and Phase 2)
Defined as the time from study drug treatment initiation to death from any cause.
Time frame: Approximately 76 months
Disease control rate (DCR) (Phase 1 and Phase 2)
Defined as the proportion of patients who achieve tumor relief (CR or PR) and stable disease (SD) after treatment; calculated as the sum of CR, PR, and SD.
Time frame: From baseline through disease progression or study completion (approximately 2 years)
Clinical benefit rate (CBR) (Phase 1 and Phase 2)
Defined as the percentage of advanced cancer patients who achieve CR, PR, or at least six months of SD after treatment.
Time frame: From baseline through disease progression or study completion (approximately 2 years)
PK Parameters: Maximum plasma concentration (Cmax) (Phase 1)
Time frame: Day 1 and Day 15 of Cycle 1 (each cycle is 28 days)
PK Parameters: Time to maximum plasma concentration (Tmax) (Phase 1)
Time frame: Day 1 and Day 15 of Cycle 1 (each cycle is 28 days)
PK Parameters: Elimination half-life (t1/2) (Phase 1)
Time frame: Day 1 and Day 15 of Cycle 1 (each cycle is 28 days)
PK Parameters: Area under the plasma concentration-time curve from time 0 to last measurable concentration (AUC 0-last) (Phase 1)
Time frame: Day 1 and Day 15 of Cycle 1 (each cycle is 28 days)
Determination of RP2D (Phase 2)
Time frame: Approximately 16 months
Number of Participants with Treatment Emergent Adverse Events (TEAEs) and lab abnormalities (Phase 2)
Time frame: From baseline until end of study treatment or study completion (approximately 2 years)
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Avenzo Therapeutics, Inc.