Treatment of advanced solid tumors with AVZO-021

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 is testing a new oral medication called AVZO-021 to see if it can safely help people with advanced solid tumors, especially certain types of breast cancer and other cancers with specific genetic changes.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 430 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Avenzo Therapeutics, Inc. (Industry-sponsored)
• Drugs / interventions: chemotherapy
• Locations: 13 sites (New Haven, Connecticut and 12 other locations)
• Trial ID: NCT05867251 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates AVZO-021, an oral medication that inhibits cyclin-dependent kinase 2 (CDK2), in patients with advanced solid tumors, particularly HR+/HER2- breast cancer and CCNE1 amplified malignancies. The study is divided into two phases: Phase 1 focuses on determining the safety, tolerability, and maximum tolerated dose of AVZO-021, while Phase 2 assesses its anti-tumor effects as both monotherapy and in combination with other treatments. The trial is multicenter and open-label, allowing for a diverse patient population to participate.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with advanced HR+/HER2- breast cancer or CCNE1 amplified tumors who have exhausted standard treatment options.

Not a fit: Patients with tumors that do not have CCNE1 amplification or those who have not failed standard therapies may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with advanced solid tumors that have limited treatment options.

How similar studies have performed: Other studies involving CDK2 inhibitors have shown promise, suggesting potential for success in this novel approach.

Eligibility 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.

Where this trial is running

New Haven, Connecticut and 12 other locations

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

Study contacts

• Study coordinator: Medical Information

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