A Phase 1/2 interventional study of AVZO-021 and Palbociclib in Advanced Solid Tumor, HR+/HER2- Breast Cancer and HR+, HER2-, Advanced Breast Cancer, sponsored by Avenzo Therapeutics, Inc.. Recruiting at 13 sites in 2 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-09-28.
Sponsored by Avenzo Therapeutics, Inc. · Phase 1/2, Interventional, and Treatment
This study, the first clinical trial of AVZO-021, aims to determine the safety, tolerability, pharmacokinetics, pharmacodynamics, maximum tolerated dose, and anti-tumor effects of AVZO-021 in patients with advanced solid tumors. AVZO-021 is an oral medication that inhibits cyclin-dependent kinase 2 (CDK 2).
AVZO-021 is a compound being developed for the treatment of patients with advanced solid tumors, specifically, HR+/HER2- breast cancer and cyclin E1 (CCNE1) altered malignancies. AVZO-021 is a selective and potent cyclin-dependent kinase 2 (CDK2) inhibitor, which plays an important role in cell cycle regulation. This is a Phase 1/2 first-in-human, open-label, nonrandomized, multicenter study of AVZO-021. Phase 1 is a dose-escalation phase aimed at assessing the safety and tolerability of AVZO-021 and determining the recommended phase 2 dose (RP2D) as monotherapy and combination therapy. Phase 2 is a dose-expansion phase that will be conducted to assess the antitumor activity of AVZO-021 as monotherapy and combination therapy.
Key Inclusion Criteria:
Disease-related inclusion criteria by study phase and part:
i) Phase 1a Monotherapy Dose Escalation: Patients with locally advanced or metastatic HR+/HER2- breast cancer, CCNE1-amplified tumors that are either epithelial ovarian cancer, primary peritoneal cancer, fallopian tube cancer, endometrial cancer or TNBC, with no other oncogenic driver mutations that are treatable and standard therapies are no longer effective, appropriate, or safe in the opinion of the investigator and medical monitor. Patients with any additional tumor type with CCNE1 amplification can be enrolled only if clinical data is supportive and approved by medical monitor (Cohort 1A).
ii) Phase 1b Combination Dose Escalation: histologically or cytologically confirmed diagnosis of locally advanced or metastatic HR+ HER2- (HER2-low may be allowed if failed standard of care therapy) breast cancer, who have been previously treated with inhibitor of CDK4/6 and endocrine therapy(Cohorts 1B1, 1B2, 1B3, 1B4, and 1B5); or histologically or cytologically confirmed diagnosis of CCNE1- amplified, locally advanced or metastatic, platinum-refractory or platinum-resistant EOC, primary peritoneal, or fallopian tube cancer (Cohort 1C).
iii) Phase 2a Monotherapy dose expansion: Histologically or cytologically confirmed diagnosis of locally advanced or metastatic CCNE1 amplified epithelial ovarian cancer, primary peritoneal cancer, fallopian tube cancer, endometrial cancer or TNBC, with no other oncogenic driver mutations that are treatable and standard therapies are no longer effective, appropriate, or safe in the opinion of the investigator and medical monitor (Cohort 2A).
iv) Phase 2b Combination dose expansion: Histologically or cytologically confirmed diagnosis of locally advanced or metastatic HR+/HER2- (HER2-low may be allowed if failed standard of care therapy) breast cancer who have been previously treated with no more than 1 prior CDK4/6 inhibitor and endocrine therapy (Cohorts 2B1, 2B2, 2B3, 2B4, and 2B5); or Histologically or cytologically confirmed diagnosis of locally advanced or metastatic, CCNE1-amplified, platinum-refractory or platinum-resistant EOC, primary peritoneal cancer, or fallopian tube cancer (Cohort 2C).
Key Exclusion Criteria:
Escalating doses of once daily, oral AVZO-021 in 28-day cycles.
Drug: AVZO-021
Escalating doses of once daily, oral AVZO-021 in 28-day cycles starting at least 1 DL below the monotherapy MTD/RP2D dose in combination with: 1B1) fulvestrant 1B2) palbociclib plus either fulvestrant or letrozole 1B3) ribociclib plus either fulvestrant or letrozole 1B4) abemaciclib plus either fulvestrant or letrozole 1B5) sacituzumab govitecan-hziy 1C) carboplatin
Drug: AVZO-021 · Drug: Palbociclib · Drug: Fulvestrant · Drug: Letrozole · Drug: Ribociclib · Drug: Abemaciclib · Drug: Carboplatin · Drug: Sacituzumab Govitecan-hziy
Oral doses of AVZO-021 in 28-day cycles at the RP2D determined in Part 1A.
Drug: AVZO-021
Oral doses of AVZO-021 in 28-day cycles at the RP2D determined in Parts 1B/1C, in combination with: 2B1) fulvestrant 2B2) palbociclib plus either fulvestrant or letrozole 2B3) ribociclib plus either fulvestrant or letrozole 2B4) abemaciclib plus either fulvestrant or letrozole 2B5) sacituzumab govitecan-hziy 2C) carboplatin
Drug: AVZO-021 · Drug: Palbociclib · Drug: Fulvestrant · Drug: Letrozole · Drug: Ribociclib · Drug: Abemaciclib · Drug: Carboplatin · Drug: Sacituzumab Govitecan-hziy
AVZO-021 is a selective and potent oral inhibitor of CDK2 being developed for the treatment of patients with advanced solid tumors with CDK2 dependency (1A), CCNE1 amplified solid tumors (2A), HR+/HER2- BC (1B1-1B5, 2B1-2B5) and CCNE1 amplified EOC (1C, 2C)
Antineoplastic agent, cyclin-dependent kinase 4/6 inhibitor
Also known as: Ibrance
Antineoplastic agent, estrogen receptor antagonist
Also known as: Faslodex
Antineoplastic agent, aromatase inhibitor
Also known as: Femara
Antineoplastic CDK4/6 inhibitor
Also known as: Kisqali
Antineoplastic CDK4/6 inhibitor
Also known as: Verzenio
Alkylating agent
Trop-2 antibody and topoisomerase inhibitor
Also known as: Trodelvy
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: 28 Days
Number of Participants with Treatment Emergent Adverse Events (TEAEs) and lab abnormalities (Phase 1)
To evaluate the type, incidence, severity, timing, seriousness, and relationship to study treatment of adverse events and any laboratory abnormalities summarized by dose level.
Time frame: Approximately 22 months
Determination of Recommended Phase 2 Dose (RP2D) (Phase 1)
RP2D for AVZO-021 is less than or the same as the maximum tolerated dose (MTD) as defined by the occurrence of DLTs and TEAEs calculated using isotonic regression.
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: Approximately 52 months
Progression Free Survival (PFS) (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: Approximately 52 months
Overall Survival (OS) (Phase 2)
Defined as the time from study drug treatment initiation to death from any cause.
Time frame: Approximately 76 months
Duration of response (DOR) (Phase 2)
Defined as the time from the first confirmed response to radiologic/objective progression.
Time frame: Approximately 52 months
PK Parameters: Maximum plasma concentration (Cmax) (monotherapy and combination)
Time frame: Cycle 1 days 1, 2, 8, 14, and 15 (each cycle is 28 days)
PK Parameters: Time to maximum plasma concentration (Tmax) (monotherapy and combination)
Time frame: Cycle 1 days 1, 2, 8, 14, and 15 (each cycle is 28 days)
PK Parameters: Area under the plasma concentration-time curve from time 0 to last measurable concentration (AUC 0-last) (monotherapy and combination)
Time frame: Cycle 1 days 1, 2, 8, 14, and 15 (each cycle is 28 days)
PK Parameters: Area under the plasma concentration-time curve from time 0 to last measurable concentration (AUC 0-tau) (monotherapy and combination)
Time frame: Cycle 1 days 1, 2, 8, 14, and 15 (each cycle is 28 days)
PK Parameters: Minimum observed plasma concentration at steady state (Cmin, ss) (monotherapy and combination)
Time frame: Cycle 1 days 1, 2, 8, 14, and 15 (each cycle is 28 days)
PK Parameters: Accumulation ration (Rac) (monotherapy and combination)
Time frame: Cycle 1 days 1, 2, 8, 14, and 15 (each cycle is 28 days)
PK Parameters: Elimination half-life (t1/2) (monotherapy and combination)
Time frame: Cycle 1 days 1, 2, 8, 14, and 15 (each cycle is 28 days)
PK Parameters: Apparent clearance (CL/F) (monotherapy and combination)
Time frame: Cycle 1 days 1, 2, 8, 14, and 15 (each cycle is 28 days)
PK Parameters: Apparent volume of distribution during terminal phase (Vz/F) (monotherapy and combination)
Time frame: Cycle 1 days 1, 2, 8, 14, and 15 (each cycle is 28 days)
Evaluate the effect of a high-fat meal on the PK of AVZO-021 (Phase 1)
Time frame: 5 days
Plan to share: No
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Carcinoma, Ovarian Epithelial→
Avenzo Therapeutics, Inc.