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NCT05867251 | RECRUITING | Advanced Solid Tumor

Study of AVZO-021 in Patients With Advanced Solid Tumors
Sponsor:

Avenzo Therapeutics, Inc.

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).

Condition or disease

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

Intervention/treatment

AVZO-021

Palbociclib

Fulvestrant

Letrozole

Ribociclib

Abemaciclib

Carboplatin

Sacituzumab Govitecan-hziy

Phase

PHASE1

PHASE2

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
Estimated Enrollment : 430 participants
Masking : NONE
Primary Purpose : TREATMENT
Official Title : 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
Actual Study Start Date : 2023-08-30
Estimated Primary Completion Date : 2028-01-31
Estimated Study Completion Date : 2030-01-31

Information not available for Arms and Intervention/treatment

Ages Eligible for Study: 18 Years
Sexes Eligible for Study: ALL
Accepts Healthy Volunteers:
Criteria
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 of AVZO-021 in Patients With Advanced Solid Tumors

Location Details

NCT05867251

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How to Participate

Want to participate in this study, select a site at your convenience, send yourself email to get contact details and prescreening steps.

Locations

RECRUITING

United States, Connecticut

Yale Cancer Center

New Haven, Connecticut, United States, 06520

RECRUITING

United States, Florida

Florida Cancer Specialists

Sarasota, Florida, United States, 34232

RECRUITING

United States, Ohio

University Hospitals Cleveland Medical Center

Cleveland, Ohio, United States, 44106

RECRUITING

United States, Oklahola

Oklahoma University

Ololama City, Okholohan, United States, 73117

RECRUITING

United States, Pennsylvania

Sidney Kimmel Cancer Center (SKCC) at Jefferson Health

Philadelphia, Pennsylvania, United States, 19107

RECRUITING

United States, Texas

Texas Oncology - DFW

Dallas, Texas, United States, 75246

RECRUITING

United States, Virginia

NEXT Virginia

Fairfax, Virginia, United States, 22031

RECRUITING

Australia, New South Wales

Macquarie University Hospital

Macquarie University, New South Wales, Australia,

RECRUITING

Australia, New South Wales

Cancer Care Wollongong

Wollongong, New South Wales, Australia,