Advanced Solid TumorPhase 1/2NCT05867251
Study of AVZO-021 in Patients With Advanced Solid Tumors
A Phase 1/2 study testing AVZO-021, Palbociclib and Fulvestrant in people with Advanced Solid Tumor and HR+/HER2- Breast Cancer, run by Avenzo Therapeutics, Inc. at 13 sites in 2 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Solid Tumor, HR+/HER2- Breast Cancer, HR+, HER2-, Advanced Breast Cancer
- What is being tested?
- AVZO-021, Palbociclib and Fulvestrant
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 430 participants
- Where
- 13 sitesin 2 countries
- Study dates
- 30 Aug 2023to 31 Jan 2030
- Phase
- Phase 1/2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female aged ≥18 years old at screening with Eastern Cooperative Oncology Group (ECOG) 0-1.
- Disease-related inclusion criteria by study phase and part:
- 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).
- 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).
- 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).
- 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).
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
13 sites in 2 countries. Contact the study team or a site near you to ask about taking part.
13 sites in 2 countries
United States11 sites, 11 recruiting
- Recruiting
Avenzo Therapeutics Recruiting Site
Cleveland, Ohio, 44106
Avenzo Therapeutics
- Recruiting
Avenzo Therapeutics Recruiting Site
Dallas, Texas, 75246
Avenzo Therapeutics
- Recruiting
Avenzo Therapeutics Recruiting Site
Fairfax, Virginia, 22031
Avenzo Therapeutics
- Recruiting
Avenzo Therapeutics Recruiting Site
Mineola, New York, 11501
Avenzo Therapeutics
- Recruiting
Avenzo Therapeutics Recruiting Site
New Haven, Connecticut, 06520
Avenzo Therapeutics
- Recruiting
Avenzo Therapeutics Recruiting Site
New York, New York, 10016
Avenzo Therapeutics
- Recruiting
Avenzo Therapeutics Recruiting Site
Oklahoma City, Oklahoma, 73117
Avenzo Therapeutics
- Recruiting
Avenzo Therapeutics Recruiting Site
Philadelphia, Pennsylvania, 19107
Avenzo Therapeutics
- Recruiting
Avenzo Therapeutics Recruiting Site
Portland, Oregon, 97213
Avenzo Therapeutics
- Recruiting
Avenzo Therapeutics Recruiting Site
Sarasota, Florida, 34232
Avenzo Therapeutics
- Recruiting
Avenzo Therapeutics Recruiting Site
Tampa, Florida, 33612
Avenzo Therapeutics
Australia2 sites, 2 recruiting
- Recruiting
Avenzo Therapeutics Recruiting Site
Macquarie University, New South Wales
Avenzo Therapeutics
- Recruiting
Avenzo Therapeutics Recruiting Site
Wollongong, New South Wales
Avenzo Therapeutics
About this study
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
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).
Read the 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.
- Conditions
- Advanced Solid Tumor, HR+/HER2- Breast Cancer, HR+, HER2-, Advanced Breast Cancer, CCNE1 Amplification, Epithelial Ovarian Cancer, Primary Peritoneal Cancer
- Being tested
- AVZO-021, Palbociclib, Fulvestrant, Letrozole, Ribociclib
- 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
- Medical subject headings
- Carcinoma, Ovarian Epithelial, Fallopian Tube Neoplasms, Endometrial Neoplasms, Triple Negative Breast Neoplasms, Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AVZO-021Drug
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)
PalbociclibDrug
Also called Ibrance
Antineoplastic agent, cyclin-dependent kinase 4/6 inhibitor
FulvestrantDrug
Also called Faslodex
Antineoplastic agent, estrogen receptor antagonist
LetrozoleDrug
Also called Femara
Antineoplastic agent, aromatase inhibitor
RibociclibDrug
Also called Kisqali
Antineoplastic CDK4/6 inhibitor
AbemaciclibDrug
Also called Verzenio
Antineoplastic CDK4/6 inhibitor
CarboplatinDrug
Alkylating agent
Sacituzumab Govitecan-hziyDrug
Also called Trodelvy
Trop-2 antibody and topoisomerase inhibitor
| Study group | Role | What they receive |
|---|---|---|
| Phase 1, monotherapy (Part 1A) | Experimental | Escalating doses of once daily, oral AVZO-021 in 28-day cycles. Receives: 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 Receives: 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. Receives: 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 Receives: Drug: AVZO-021; Drug: Palbociclib; Drug: Fulvestrant; Drug: Letrozole; Drug: Ribociclib; Drug: Abemaciclib; Drug: Carboplatin; Drug: Sacituzumab Govitecan-hziy |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Approximately 52 months
Overall Survival (OS) (Phase 2)
Defined as the time from study drug treatment initiation to death from any cause.
Measured: Approximately 76 months
Duration of response (DOR) (Phase 2)
Defined as the time from the first confirmed response to radiologic/objective progression.
Measured: Approximately 52 months
Secondary outcomes (10)
PK Parameters: Maximum plasma concentration (Cmax) (monotherapy and combination)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: Cycle 1 days 1, 2, 8, 14, and 15 (each cycle is 28 days)
PK Parameters: Accumulation ration (Rac) (monotherapy and combination)
Measured: Cycle 1 days 1, 2, 8, 14, and 15 (each cycle is 28 days)
PK Parameters: Elimination half-life (t1/2) (monotherapy and combination)
Measured: Cycle 1 days 1, 2, 8, 14, and 15 (each cycle is 28 days)
PK Parameters: Apparent clearance (CL/F) (monotherapy and combination)
Measured: 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)
Measured: 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)
Measured: 5 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 May 2023
- Study start30 Aug 2023
- Primary completion31 Jan 2028 (estimated)
- Study completion31 Jan 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced Solid TumorStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Model description
- Phase 1 dose-escalation Phase 2 dose-expansion
- Masking
- None (open label)
- Enrolment
- 430 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Avenzo Therapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05867251
- Sponsor's protocol ID
- AVZO-021-1001
- Status last verified
- Sep 2026
- First submitted
- 13 Apr 2023
- Last updated
- 28 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No