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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05867251




Registration number
NCT05867251
Ethics application status
Date submitted
13/04/2023
Date registered
19/05/2023
Date last updated
27/12/2024

Titles & IDs
Public title
Study of AVZO-021 in Patients with Advanced Solid Tumors
Scientific 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
Secondary ID [1] 0 0
AVZO-021-1001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Advanced Solid Tumor 0 0
HR+/HER2- Breast Cancer 0 0
HR+, HER2-, Advanced Breast Cancer 0 0
CCNE1 Amplification 0 0
Epithelial Ovarian Cancer 0 0
Primary Peritoneal Cancer 0 0
Fallopian Tube Cancer 0 0
Endometrial Cancer 0 0
TNBC - Triple-Negative Breast Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Breast
Cancer 0 0 0 0
Ovarian and primary peritoneal
Cancer 0 0 0 0
Womb (Uterine or endometrial cancer)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - AVZO-021
Treatment: Drugs - Palbociclib
Treatment: Drugs - Fulvestrant
Treatment: Drugs - Letrozole
Treatment: Drugs - Ribociclib
Treatment: Drugs - Abemaciclib
Treatment: Drugs - Carboplatin
Treatment: Drugs - Sacituzumab Govitecan-hziy

Experimental: Phase 1, monotherapy (Part 1A) - Escalating doses of once daily, oral AVZO-021 in 28-day cycles.

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

Experimental: Phase 2, monotherapy (Part 2A) - Oral doses of AVZO-021 in 28-day cycles at the RP2D determined in Part 1A.

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


Treatment: Drugs: AVZO-021
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)

Treatment: Drugs: Palbociclib
Antineoplastic agent, cyclin-dependent kinase 4/6 inhibitor

Treatment: Drugs: Fulvestrant
Antineoplastic agent, estrogen receptor antagonist

Treatment: Drugs: Letrozole
Antineoplastic agent, aromatase inhibitor

Treatment: Drugs: Ribociclib
Antineoplastic CDK4/6 inhibitor

Treatment: Drugs: Abemaciclib
Antineoplastic CDK4/6 inhibitor

Treatment: Drugs: Carboplatin
Alkylating agent

Treatment: Drugs: Sacituzumab Govitecan-hziy
Trop-2 antibody and topoisomerase inhibitor
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Occurrence of Dose Limiting Toxicities (DLTs) during the first cycle (Phase 1)
Timepoint [1] 0 0
28 Days
Primary outcome [2] 0 0
Number of Participants with Treatment Emergent Adverse Events (TEAEs) and lab abnormalities (Phase 1)
Timepoint [2] 0 0
Approximately 22 months
Primary outcome [3] 0 0
Determination of Recommended Phase 2 Dose (RP2D) (Phase 1)
Timepoint [3] 0 0
Approximately 16 months
Primary outcome [4] 0 0
Objective Response Rate (ORR) (Phase 2)
Timepoint [4] 0 0
Approximately 52 months
Primary outcome [5] 0 0
Progression Free Survival (PFS) (Phase 2)
Timepoint [5] 0 0
Approximately 52 months
Primary outcome [6] 0 0
Overall Survival (OS) (Phase 2)
Timepoint [6] 0 0
Approximately 76 months
Primary outcome [7] 0 0
Duration of response (DOR) (Phase 2)
Timepoint [7] 0 0
Approximately 52 months
Secondary outcome [1] 0 0
PK Parameters: Maximum plasma concentration (Cmax) (monotherapy and combination)
Timepoint [1] 0 0
Cycle 1 days 1, 2, 8, 14, and 15 (each cycle is 28 days)
Secondary outcome [2] 0 0
PK Parameters: Time to maximum plasma concentration (Tmax) (monotherapy and combination)
Timepoint [2] 0 0
Cycle 1 days 1, 2, 8, 14, and 15 (each cycle is 28 days)
Secondary outcome [3] 0 0
PK Parameters: Area under the plasma concentration-time curve from time 0 to last measurable concentration (AUC 0-last) (monotherapy and combination)
Timepoint [3] 0 0
Cycle 1 days 1, 2, 8, 14, and 15 (each cycle is 28 days)
Secondary outcome [4] 0 0
PK Parameters: Area under the plasma concentration-time curve from time 0 to last measurable concentration (AUC 0-tau) (monotherapy and combination)
Timepoint [4] 0 0
Cycle 1 days 1, 2, 8, 14, and 15 (each cycle is 28 days)
Secondary outcome [5] 0 0
PK Parameters: Minimum observed plasma concentration at steady state (Cmin, ss) (monotherapy and combination)
Timepoint [5] 0 0
Cycle 1 days 1, 2, 8, 14, and 15 (each cycle is 28 days)
Secondary outcome [6] 0 0
PK Parameters: Accumulation ration (Rac) (monotherapy and combination)
Timepoint [6] 0 0
Cycle 1 days 1, 2, 8, 14, and 15 (each cycle is 28 days)
Secondary outcome [7] 0 0
PK Parameters: Elimination half-life (t1/2) (monotherapy and combination)
Timepoint [7] 0 0
Cycle 1 days 1, 2, 8, 14, and 15 (each cycle is 28 days)
Secondary outcome [8] 0 0
PK Parameters: Apparent clearance (CL/F) (monotherapy and combination)
Timepoint [8] 0 0
Cycle 1 days 1, 2, 8, 14, and 15 (each cycle is 28 days)
Secondary outcome [9] 0 0
PK Parameters: Apparent volume of distribution during terminal phase (Vz/F) (monotherapy and combination)
Timepoint [9] 0 0
Cycle 1 days 1, 2, 8, 14, and 15 (each cycle is 28 days)
Secondary outcome [10] 0 0
Evaluate the effect of a high-fat meal on the PK of AVZO-021 (Phase 1)
Timepoint [10] 0 0
5 days

Eligibility
Key inclusion criteria
Key

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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
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 design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
30/08/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
31/01/2030
Actual
Sample size
Target
430
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
Macquarie University Hospital - Macquarie University
Recruitment hospital [2] 0 0
Cancer Care Wollongong - Wollongong
Recruitment postcode(s) [1] 0 0
- Macquarie University
Recruitment postcode(s) [2] 0 0
- Wollongong
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Connecticut
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Ohio
Country [4] 0 0
United States of America
State/province [4] 0 0
Oklahoma
Country [5] 0 0
United States of America
State/province [5] 0 0
Pennsylvania
Country [6] 0 0
United States of America
State/province [6] 0 0
Virginia

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Avenzo Therapeutics, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
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).
Trial website
https://clinicaltrials.gov/study/NCT05867251
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Medical Information
Address 0 0
Country 0 0
Phone 0 0
(858) 239-2944
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT05867251