Trial Title:
Study of AVZO-021 in Patients With Advanced Solid Tumors
NCT ID:
NCT05867251
Condition:
Advanced Solid Tumor
Conditions: Official terms:
Neoplasms
Carboplatin
Letrozole
Fulvestrant
Palbociclib
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Sequential Assignment
Intervention model description:
Phase 1 dose-escalation Phase 2 dose-expansion
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
AVZO-021
Description:
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 (B1-B4) and CCNE1 amplified EOC (C)
Arm group label:
Phase 1, combination (Parts 1B and 1C)
Arm group label:
Phase 1, monotherapy (Part 1A)
Arm group label:
Phase 2, combination (Parts 2B and 2C)
Arm group label:
Phase 2, monotherapy (Part 2A)
Intervention type:
Drug
Intervention name:
Palbociclib
Description:
Antineoplastic agent, cyclin-dependent kinase 4/6 inhibitor
Arm group label:
Phase 1, combination (Parts 1B and 1C)
Arm group label:
Phase 2, combination (Parts 2B and 2C)
Other name:
Ibrance
Intervention type:
Drug
Intervention name:
Fulvestrant
Description:
Antineoplastic agent, estrogen receptor antagonist
Arm group label:
Phase 1, combination (Parts 1B and 1C)
Arm group label:
Phase 2, combination (Parts 2B and 2C)
Other name:
Faslodex
Intervention type:
Drug
Intervention name:
Letrozole
Description:
Antineoplastic agent, aromatase inhibitor
Arm group label:
Phase 1, combination (Parts 1B and 1C)
Arm group label:
Phase 2, combination (Parts 2B and 2C)
Other name:
Femara
Intervention type:
Drug
Intervention name:
Ribociclib
Description:
Antineoplastic CDK4/6 inhibitor
Arm group label:
Phase 1, combination (Parts 1B and 1C)
Arm group label:
Phase 2, combination (Parts 2B and 2C)
Other name:
Kisqali
Intervention type:
Drug
Intervention name:
Abemaciclib
Description:
Antineoplastic CDK4/6 inhibitor
Arm group label:
Phase 1, combination (Parts 1B and 1C)
Arm group label:
Phase 2, combination (Parts 2B and 2C)
Other name:
Verzenio
Intervention type:
Drug
Intervention name:
Carboplatin
Description:
Alkylating agent
Arm group label:
Phase 1, combination (Parts 1B and 1C)
Arm group label:
Phase 2, combination (Parts 2B and 2C)
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).
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.
Criteria for 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: Locally advanced or metastatic solid tumor
associated with dependency on CDK2 (eg, HR+/HER2- breast cancer, CCNE1 amplified
solid tumors, FBXW7 loss of function mutation/deletion and retinoblastoma protein
(Rb)1 loss of function mutation/deletion), for which standard therapies are no
longer effective, appropriate, or safe in the opinion of the investigator (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 in patients who have been previously
treated with inhibitor of CDK4/6 and endocrine therapy (Cohorts 1B1, 1B2, 1B3, and
1B4); or Histologically or cytologically confirmed diagnosis of CCNE1 amplified
locally advanced or metastatic EOC in patients who are platinum-refractory or
platinum-resistant (Cohort 1C).
iii) Phase 2a Monotherapy dose expansion: Histologically or cytologically confirmed
diagnosis of locally advanced or metastatic CCNE1 amplified solid tumors 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,
and 2B4); or Histologically or cytologically confirmed diagnosis of CCNE1 amplified
locally advanced or metastatic EOC in patients who are platinum-refractory or
platinum-resistant (Cohort 2C).
3. No more than 2 prior cytotoxic chemotherapy regimens for locally advanced/metastatic
disease (prior chemotherapy in the adjuvant or neoadjuvant setting allowed if >12
months prior to starting AVZO-021 treatment and is not considered a prior line).
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.
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.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Yale Cancer Center
Address:
City:
New Haven
Zip:
06520
Country:
United States
Status:
Recruiting
Contact:
Last name:
Yale Cancer Center
Facility:
Name:
Florida Cancer Specialists
Address:
City:
Sarasota
Zip:
34232
Country:
United States
Status:
Recruiting
Contact:
Last name:
Florida Cancer Specialists
Facility:
Name:
University Hospitals Cleveland Medical Center
Address:
City:
Cleveland
Zip:
44106
Country:
United States
Status:
Recruiting
Contact:
Last name:
University Hospitals Cleveland Medical Center
Facility:
Name:
Oklahoma University
Address:
City:
Oklahoma City
Zip:
73117
Country:
United States
Status:
Recruiting
Contact:
Last name:
Oklahoma University
Facility:
Name:
Sidney Kimmel Cancer Center (SKCC) at Jefferson Health
Address:
City:
Philadelphia
Zip:
19107
Country:
United States
Status:
Recruiting
Contact:
Last name:
Sidney Kimmel Cancer Center (SKCC)
Facility:
Name:
NEXT Virginia
Address:
City:
Fairfax
Zip:
22031
Country:
United States
Status:
Recruiting
Contact:
Last name:
NEXT Virginia
Start date:
August 30, 2023
Completion date:
January 31, 2030
Lead sponsor:
Agency:
Avenzo Therapeutics, Inc.
Agency class:
Industry
Source:
Avenzo Therapeutics, Inc.
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05867251
