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Study of AVZO-021 in Patients With Advanced Solid Tumors

PHASE1PHASE2RECRUITING

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 details:

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.

Eligibility criteria

Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.

Inclusion criteria

  1. Male or female aged ≥18 years old at screening with Eastern Cooperative Oncology Group (ECOG) 0-1.
  2. 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.
  3. 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; 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.
  4. 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.
  5. 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; 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.
  6. 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).
  7. Measurable disease as determined by RECIST version 1.1.
  8. Adequate bone marrow and organ function.
  9. Ability to swallow capsules or tablets.

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.

Eligibility

Age eligible for study : NA

Healthy volunteers accepted : No

Gender eligible for study: ALL

Things to know

Study dates

Study start:

Primary completion:

Study completion finish:

study type

Study type

TREATMENT

phase

Phase

    PHASE1PHASE2

trial

Study ID

NCT05867251

Intervention or treatment

DRUG: AVZO-021

DRUG: Palbociclib

DRUG: Fulvestrant

DRUG: Letrozole

DRUG: Ribociclib

DRUG: Abemaciclib

DRUG: Carboplatin

DRUG: Sacituzumab Govitecan-hziy

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

  • Condition: Advanced Solid Tumor, HR+/HER2- Breast Cancer and more

  • DRUG: AVZO-021 and other drugs

  • Macquarie University, New South Wales, Australia and more

  • Sponsor: Avenzo Therapeutics, Inc.

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Are you running this trial?

If you're a clinic or sponsor, you can claim this study

Research sites nearby

Closest Location:

Macquarie University Hospital

Select from list below to view details:

  • Macquarie University Hospital

    Macquarie University, New South Wales, Australia

  • Cancer Care Wollongong

    Wollongong, New South Wales, Australia

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Who is running the clinical trial?

ATI

Avenzo Therapeutics, Inc.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Participant Group/ArmIntervention/Treatment
EXPERIMENTAL: Phase 1, monotherapy (Part 1A)
  • Escalating doses of once daily, oral AVZO-021 in 28-day cycles.
Drug: AVZO-021
    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: AVZO-021, Drug: Palbociclib, Drug: Fulvestrant, Drug: Letrozole, Drug: Ribociclib, Drug: Abemaciclib, Drug: Carboplatin, Drug: Sacituzumab Govitecan-hziy
      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
        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: AVZO-021, Drug: Palbociclib, Drug: Fulvestrant, Drug: Letrozole, Drug: Ribociclib, Drug: Abemaciclib, Drug: Carboplatin, Drug: Sacituzumab Govitecan-hziy

          What is the study measuring?

          Primary Outcome

          MeasureDescriptionTime 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

          MeasureDescriptionTime Frame
          PK Parameters: Maximum plasma concentration (Cmax) (monotherapy and combination)Not SpecifiedCycle 1 days 1, 2, 8, 14, and 15 (each cycle is 28 days)
          PK Parameters: Time to maximum plasma concentration (Tmax) (monotherapy and combination)Not SpecifiedCycle 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)Not SpecifiedCycle 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)Not SpecifiedCycle 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)Not SpecifiedCycle 1 days 1, 2, 8, 14, and 15 (each cycle is 28 days)
          PK Parameters: Accumulation ration (Rac) (monotherapy and combination)Not SpecifiedCycle 1 days 1, 2, 8, 14, and 15 (each cycle is 28 days)
          PK Parameters: Elimination half-life (t1/2) (monotherapy and combination)Not SpecifiedCycle 1 days 1, 2, 8, 14, and 15 (each cycle is 28 days)
          PK Parameters: Apparent clearance (CL/F) (monotherapy and combination)Not SpecifiedCycle 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)Not SpecifiedCycle 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)Not Specified5 days
          Are you running this trial?If you're a clinic or sponsor, you can claim this study.
          Claim this trial

          References

          Clinical Trials Gov: Study of AVZO-021 in Patients With Advanced Solid Tumors

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