Study of AVZO-021 in Patients With Advanced Solid Tumors

NCT05867251 | Recruiting Phase 1 FDA Drug

• 1 other identifier: AVZO-021-1001
• Study Type: interventional
• Target: 430
• Locations: 2 countries
• Sites: 13

Brief Summary

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).

Conditions

Advanced Solid Tumor; HR+/HER2- Breast Cancer; HR+, HER2-, Advanced Breast Cancer; CCNE1 Amplification; Epithelial Ovarian Cancer; Primary Peritoneal Cancer; Fallopian Tube Cancer; Endometrial Cancer; TNBC - Triple-Negative Breast Cancer

Keywords

Advanced solid tumor; HR+/HER2- Breast Cancer; Breast Cancer; Advanced Breast Cancer; CCNE1 Amplification; Epithelial Ovarian Cancer; Primary Peritoneal Cancer; Fallopian Tube Cancer; Endometrial Cancer; Triple Negative Breast Cancer

Outcome Measures

Primary Outcomes (7)

• 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 Outcomes (10)

• 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)

Study Arms (4)

Phase 1, monotherapy (Part 1A)

EXPERIMENTAL

Escalating doses of once daily, oral AVZO-021 in 28-day cycles.

Drug: AVZO-021

Phase 1, combination (Parts 1B and 1C)

EXPERIMENTAL

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

Phase 2, monotherapy (Part 2A)

EXPERIMENTAL

Oral doses of AVZO-021 in 28-day cycles at the RP2D determined in Part 1A.

Drug: AVZO-021

Phase 2, combination (Parts 2B and 2C)

EXPERIMENTAL

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

Interventions

AVZO-021 DRUG

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)

Phase 1, combination (Parts 1B and 1C); Phase 1, monotherapy (Part 1A); Phase 2, combination (Parts 2B and 2C); Phase 2, monotherapy (Part 2A)

Palbociclib DRUG

Antineoplastic agent, cyclin-dependent kinase 4/6 inhibitor

Also known as: Ibrance

Phase 1, combination (Parts 1B and 1C); Phase 2, combination (Parts 2B and 2C)

Fulvestrant DRUG

Antineoplastic agent, estrogen receptor antagonist

Also known as: Faslodex

Phase 1, combination (Parts 1B and 1C); Phase 2, combination (Parts 2B and 2C)

Letrozole DRUG

Antineoplastic agent, aromatase inhibitor

Also known as: Femara

Phase 1, combination (Parts 1B and 1C); Phase 2, combination (Parts 2B and 2C)

Ribociclib DRUG

Antineoplastic CDK4/6 inhibitor

Also known as: Kisqali

Phase 1, combination (Parts 1B and 1C); Phase 2, combination (Parts 2B and 2C)

Abemaciclib DRUG

Antineoplastic CDK4/6 inhibitor

Also known as: Verzenio

Phase 1, combination (Parts 1B and 1C); Phase 2, combination (Parts 2B and 2C)

Carboplatin DRUG

Alkylating agent

Phase 1, combination (Parts 1B and 1C); Phase 2, combination (Parts 2B and 2C)

Sacituzumab Govitecan-hziy DRUG

Trop-2 antibody and topoisomerase inhibitor

Also known as: Trodelvy

Phase 1, combination (Parts 1B and 1C); Phase 2, combination (Parts 2B and 2C)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female aged ≥18 years old at screening with Eastern Cooperative Oncology Group (ECOG) 0-1.
• 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).
• 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).
• Measurable disease as determined by RECIST version 1.1.
• Adequate bone marrow and organ function.
• Ability to swallow capsules or tablets.

You may not qualify if:

• 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.
• 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.
• Undergone major surgery within 4 weeks prior to planned start of AVZO-021.
• Received radiotherapy for palliation within 7 days of the first dose of study treatment, unless specified otherwise in the protocol.
• Active CNS metastases or confirmed leptomeningeal disease are not eligible.
• 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.
• Clinically unstable cardiac function as described in the protocol.
• Any active or chronic infection/disease that compromises the immune system.
• Current treatment with strong or moderate cytochrome P450 (CYP)3A4 inhibitors or inducers.
• Active second malignancy unless in remission with life expectancy \> 2 years and with documented sponsor approval.
• Pregnancy, lactation, or plans to breastfeed during the study or within 6 months of the last dose of study intervention.

Sponsors & Collaborators

• Avenzo Therapeutics, Inc.: lead

Study Sites (13)

Yale Cancer Center

New Haven, Connecticut, 06520, United States

RECRUITING

Florida Cancer Specialists

Sarasota, Florida, 34232, United States

RECRUITING

Moffitt Cancer Center

Tampa, Florida, 33612, United States

RECRUITING

Perlmutter Cancer Center at NYU Langone Hospital - Long Island

Mineola, New York, 11501, United States

RECRUITING

NYU Langone Medical Center (Tisch Hospital)

New York, New York, 10016, United States

RECRUITING

University Hospitals Cleveland Medical Center

Cleveland, Ohio, 44106, United States

RECRUITING

Oklahoma University

Oklahoma City, Oklahoma, 73117, United States

RECRUITING

Providence Cancer Institute

Portland, Oregon, 97213, United States

RECRUITING

Sidney Kimmel Cancer Center (SKCC) at Jefferson Health

Philadelphia, Pennsylvania, 19107, United States

RECRUITING

Texas Oncology - DFW

Dallas, Texas, 75246, United States

RECRUITING

NEXT Virginia

Fairfax, Virginia, 22031, United States

RECRUITING

Macquarie University Hospital

Macquarie University, New South Wales, Australia

RECRUITING

Cancer Care Wollongong

Wollongong, New South Wales, Australia

RECRUITING

MeSH Terms

Conditions

Carcinoma, Ovarian Epithelial; Fallopian Tube Neoplasms; Endometrial Neoplasms; Triple Negative Breast Neoplasms; Breast Neoplasms

Interventions

palbociclib; Fulvestrant; Letrozole; ribociclib; abemaciclib; Carboplatin; sacituzumab govitecan

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Ovarian Neoplasms; Endocrine Gland Neoplasms; Neoplasms by Site; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Fallopian Tube Diseases; Uterine Neoplasms; Uterine Diseases; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Coordination Complexes

Central Study Contacts

Medical Information

CONTACT

(858) 239-2944; ClinicalTrials@avenzotx.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Phase 1 dose-escalation Phase 2 dose-expansion

Study Record Dates

• First Submitted: April 13, 2023
• First Posted: May 19, 2023
• Study Start: August 30, 2023
• Primary Completion (Estimated): January 31, 2028
• Study Completion (Estimated): January 31, 2030
• Last Updated: November 19, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (11); AU (2)