Study of AVZO-021 in Patients With Advanced Solid Tumors

A Phase 1/2, First-in-Human Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Antitumor Activity of AVZO-021 as a Single Agent and in Combination Therapy in Patients With Advanced Solid Tumors

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).

Study Overview

• Status: Recruiting
• Conditions: Fallopian Tube Cancer; Advanced Solid Tumor; Endometrial Cancer; Epithelial Ovarian Cancer; Primary Peritoneal Cancer; TNBC - Triple-Negative Breast Cancer; CCNE1 Amplification; HR+/HER2- Breast Cancer; HR+, HER2-, Advanced Breast Cancer
• Intervention / Treatment: Drug: Carboplatin; Drug: Palbociclib; Drug: Fulvestrant; Drug: Letrozole; Drug: Ribociclib; Drug: Abemaciclib; Drug: AVZO-021; Drug: Sacituzumab Govitecan-hziy

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 430
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Medical Information; Phone Number: (858) 239-2944; Email: ClinicalTrials@avenzotx.com

Study Locations

• Australia
  • New South Wales
    • Macquarie University, New South Wales, Australia
      • Recruiting
      • Macquarie University Hospital
      • Contact: Macquarie University Hospital
    • Wollongong, New South Wales, Australia
      • Recruiting
      • Cancer Care Wollongong
      • Contact: Cancer Care Wollongong
• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Recruiting
      • Yale Cancer Center
      • Contact: Yale Cancer Center
  • Florida
    • Sarasota, Florida, United States, 34232
      • Recruiting
      • Florida Cancer Specialists
      • Contact: Florida Cancer Specialists
    • Tampa, Florida, United States, 33612
      • Recruiting
      • Moffitt Cancer Center
      • Contact: Moffitt Cancer Center
  • New York
    • Mineola, New York, United States, 11501
      • Recruiting
      • Perlmutter Cancer Center at NYU Langone Hospital - Long Island
      • Contact: Perlmutter Cancer Center at NYU Langone Hospital - Long Island
    • New York, New York, United States, 10016
      • Recruiting
      • NYU Langone Medical Center (Tisch Hospital)
      • Contact: NYU Langone Medical Center (Tisch Hospital)
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • Recruiting
      • University Hospitals Cleveland Medical Center
      • Contact: University Hospitals Cleveland Medical Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73117
      • Recruiting
      • Oklahoma University
      • Contact: Oklahoma University
  • Oregon
    • Portland, Oregon, United States, 97213
      • Recruiting
      • Providence Cancer Institute
      • Contact: Providence Cancer Institute
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Recruiting
      • Sidney Kimmel Cancer Center (SKCC) at Jefferson Health
      • Contact: Sidney Kimmel Cancer Center (SKCC)
  • Texas
    • Dallas, Texas, United States, 75246
      • Recruiting
      • Texas Oncology - DFW
      • Contact: Texas Oncology - DFW
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Recruiting
      • NEXT Virginia
      • Contact: NEXT Virginia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

1. Male or female aged ≥18 years old at screening with Eastern Cooperative Oncology Group (ECOG) 0-1.

2. 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).

3. No more than 2 prior cytotoxic chemotherapy regimens for locally advanced/metastatic disease (excepting patients treated with an antibody-drug conjugate, with ovarian cancer if there disease is platinum resistant or refractory, having progressed beyond all SOC care; and patients who have received prior chemotherapy in the adjuvant or neoadjuvant setting >12 months prior to starting AVZO-021 treatment).
4. Measurable disease as determined by RECIST version 1.1.
5. Adequate bone marrow and organ function.
6. Ability to swallow capsules or tablets.

Key Exclusion Criteria:

1. Received an investigational agent or anticancer therapy within 2 weeks, or 5 half-lives of the drug, whichever is shorter, prior to planned start of AVZO-021.
2. Received any CDK2 inhibitor, protein kinase membrane associated tyrosine/threonine 1 (PKMYT1) inhibitor, or WEE1 inhibitor anticancer therapy. For cohort B5, prior therapy with topoisomerase inhibitors is not permitted.
3. Undergone major surgery within 4 weeks prior to planned start of AVZO-021.
4. Received radiotherapy for palliation within 7 days of the first dose of study treatment, unless specified otherwise in the protocol.
5. Active CNS metastases or confirmed leptomeningeal disease are not eligible.
6. Unresolved toxicities from prior therapy greater than Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 Grade >1 at the time of starting study treatment.
7. Clinically unstable cardiac function as described in the protocol.
8. Any active or chronic infection/disease that compromises the immune system.
9. Current treatment with strong or moderate cytochrome P450 (CYP)3A4 inhibitors or inducers.
10. Active second malignancy unless in remission with life expectancy > 2 years and with documented sponsor approval.
11. Pregnancy, lactation, or plans to breastfeed during the study or within 6 months of the last dose of study intervention.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase 1, monotherapy (Part 1A); Escalating doses of once daily, oral AVZO-021 in 28-day cycles.	Drug: AVZO-021; 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)
Experimental: Phase 2, monotherapy (Part 2A); Oral doses of AVZO-021 in 28-day cycles at the RP2D determined in Part 1A.	Drug: AVZO-021; 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)
Experimental: Phase 1, combination (Parts 1B and 1C); 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: Carboplatin; Alkylating agent; Drug: Palbociclib; Antineoplastic agent, cyclin-dependent kinase 4/6 inhibitor; Other Names: Ibrance; Drug: Fulvestrant; Antineoplastic agent, estrogen receptor antagonist; Other Names: Faslodex; Drug: Letrozole; Antineoplastic agent, aromatase inhibitor; Other Names: Femara; Drug: Ribociclib; Antineoplastic CDK4/6 inhibitor; Other Names: Kisqali; Drug: Abemaciclib; Antineoplastic CDK4/6 inhibitor; Other Names: Verzenio; Drug: AVZO-021; 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); Drug: Sacituzumab Govitecan-hziy; Trop-2 antibody and topoisomerase inhibitor; Other Names: Trodelvy
Experimental: Phase 2, combination (Parts 2B and 2C); 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: Carboplatin; Alkylating agent; Drug: Palbociclib; Antineoplastic agent, cyclin-dependent kinase 4/6 inhibitor; Other Names: Ibrance; Drug: Fulvestrant; Antineoplastic agent, estrogen receptor antagonist; Other Names: Faslodex; Drug: Letrozole; Antineoplastic agent, aromatase inhibitor; Other Names: Femara; Drug: Ribociclib; Antineoplastic CDK4/6 inhibitor; Other Names: Kisqali; Drug: Abemaciclib; Antineoplastic CDK4/6 inhibitor; Other Names: Verzenio; Drug: AVZO-021; 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); Drug: Sacituzumab Govitecan-hziy; Trop-2 antibody and topoisomerase inhibitor; Other Names: Trodelvy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	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.	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.	Approximately 52 months
Overall Survival (OS) (Phase 2)	Defined as the time from study drug treatment initiation to death from any cause.	Approximately 76 months
Duration of response (DOR) (Phase 2)	Defined as the time from the first confirmed response to radiologic/objective progression.	Approximately 52 months

Secondary Outcome Measures

Outcome Measure	Time Frame
PK Parameters: Maximum plasma concentration (Cmax) (monotherapy and combination)	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)	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)	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)	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)	Cycle 1 days 1, 2, 8, 14, and 15 (each cycle is 28 days)
PK Parameters: Accumulation ration (Rac) (monotherapy and combination)	Cycle 1 days 1, 2, 8, 14, and 15 (each cycle is 28 days)
PK Parameters: Elimination half-life (t1/2) (monotherapy and combination)	Cycle 1 days 1, 2, 8, 14, and 15 (each cycle is 28 days)
PK Parameters: Apparent clearance (CL/F) (monotherapy and combination)	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)	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)	5 days

Collaborators and Investigators

• Sponsor: Avenzo Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): August 30, 2023
• Primary Completion (Estimated): January 31, 2028
• Study Completion (Estimated): January 31, 2030

Study Registration Dates

• First Submitted: April 13, 2023
• First Submitted That Met QC Criteria: May 17, 2023
• First Posted (Actual): May 19, 2023

Study Record Updates

• Last Update Posted (Actual): November 19, 2025
• Last Update Submitted That Met QC Criteria: November 17, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: Breast Cancer; Advanced Breast Cancer; Epithelial Ovarian Cancer; Endometrial Cancer; Triple Negative Breast Cancer; Advanced solid tumor; Fallopian Tube Cancer; Primary Peritoneal Cancer; HR+/HER2- Breast Cancer; CCNE1 Amplification
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Endocrine System Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Neoplasms by Histologic Type; Uterine Diseases; Genital Diseases, Female; Endocrine Gland Neoplasms; Neoplasms, Glandular and Epithelial; Ovarian Diseases; Adnexal Diseases; Genital Neoplasms, Female; Gonadal Disorders; Skin Diseases; Breast Diseases; Carcinoma; Uterine Neoplasms; Fallopian Tube Diseases; Ovarian Neoplasms; Skin and Connective Tissue Diseases; Carcinoma, Ovarian Epithelial; Breast Neoplasms; Triple Negative Breast Neoplasms; Endometrial Neoplasms; Fallopian Tube Neoplasms; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Azoles; Polycyclic Compounds; Coordination Complexes; Steroids; Fused-Ring Compounds; Nitriles; Estradiol; Estrenes; Estranes; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Triazoles; Letrozole; Fulvestrant; Carboplatin; abemaciclib; ribociclib; palbociclib; sacituzumab govitecan
• Other Study ID Numbers: AVZO-021-1001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No