Clinical trial NCT06998407: Study of AVZO-023 as a Single Agent and in Combination With AVZO-021, and/or Endocrine Therapy in Advanced Solid Tumors
Official title: A Phase 1/2, First-in-human Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Antitumor Activity of AVZO-023 as a Single Agent, and in Combination With AVZO-021 and/or Endocrine Therapy in Patients With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Advanced Solid Tumor
HR+/HER2- Breast Cancer
HR+, HER2-, Advanced Breast Cancer
CDK Gene Mutation
CCND1 Gene Amplification
CDK4 Gene Amplification
Lead sponsor: Avenzo Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2025-05-31
Enrollment: 380
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Phase 1 dose-escalation Phase 2 dose-expansion
Primary purpose: TREATMENT

Brief summary: This study, the first clinical trial of AVZO-023, aims to determine the safety, tolerability, pharmacokinetics (PK), pharmacodynamics, maximum tolerated dose, and anti-tumor effects of AVZO-023 in patients with advanced solid tumors. AVZO-023 is an oral medication that inhibits cyclin-dependent kinase 4 (CDK4).

Detailed description: AVZO-023 is an oral, potent, and selective inhibitor of CDK4. AVZO-021 is an oral, potent, and selective inhibitor of CDK2 that is currently being investigated in a global Phase 1/2 study in patients with advanced hormone receptive positive (HR+)/human epidermal growth factor receptor 2 negative (HER2-) breast cancer and cyclin E1 protein (CCNE1)-amplified malignancies (NCT05867251).

In Phase 1, the safety and tolerability of AVZO-023 in patients with advanced solid tumors that are CDK4/CCND1 amplified and in patients with HR+/HER2- locally advanced or metastatic breast cancer (mBC) will be assessed. The goal of Phase 1 is to determine the MTD/preliminary RP2D of AVZO-023 for use as monotherapy and in combination with AVZO-021 with or without endocrine therapy (ET).

Phase 2 will assess the antitumor activity and confirm the RP2D of AVZO-023 in combination therapy in patients with HR+/HER2- locally advanced or mBC.

Eligibility criteria: Key Inclusion Criteria:

* Male or female aged ≥ 18 years old at screening with Eastern Cooperative Oncology Group (ECOG) 0-1 and life expectancy \> 3 months
* Patients with histologically or cytologically proven advanced malignancies of preferred indications
* Measurable disease (as assessed by investigator using RECIST v1.1) is preferred in Phase 1 dose escalation, unless otherwise specified in the protocol, and in all patients in Phase 2. For patients with HR+/HER2- breast cancer enrolled in dose escalation, bone only disease is allowed
* Agree to provide molecular test report results to confirm eligibility and archival tumor samples and/or fresh biopsy, as applicable
* Adequate renal, liver, and bone marrow function

Key Exclusion Criteria:

* Patients should not have received prior selective CDK (CDK2, CDK4, CDK2/4, CDK2/4/6) inhibitors
* Has known active brain metastasis (have either previously untreated intracranial CNS metastasis or previously treated intracranial central nervous system (CNS) metastasis with radiologically documented new or progressing CNS lesions) or leptomeningeal disease
* Other concurrent invasive malignancy or a prior invasive malignancy for which treatment was completed within 3 years before the first dose on study except for adequately treated basal cell or squamous cell skin cancer, carcinoma in situ, or colorectal adenomatous polyps
* Last anticancer treatment within 2 weeks (4 weeks for biologic, immunotherapy or ADC) or 5 half-lives of the drug, whichever is shorter, prior to first dose on study
* Major surgery within 4 weeks prior to first dose on study
* Have received radiotherapy with a limited field of radiation for palliation within 7 days of the first dose of study treatment, except for patients receiving whole brain radiotherapy, which must be completed at least 4 weeks prior to the first dose of study treatment. Patients must have recovered from all radiation-related toxicities, not require corticosteroids, and not have active radiation pneumonitis
* Strong or moderate CYP3A4 inhibitors or inducers within 2 weeks or 5 half-lives of the drug, whichever is shorter, prior to first dose on study
* History of serious cardiovascular conditions within 6 months prior to first dose on study
* Unresolved toxicities from prior therapy greater than Grade 1 (per CTCAE version 5.0) (with exceptions of alopecia, vitiligo, and ≤ Grade 2 peripheral neuropathy) prior to the first dose on study
* History of drug-induced pneumonitis/interstitial lung disease

Primary outcomes:
measure: Occurrence of Dose Limiting Toxicities (DLTs) during the first cycle (Phase 1)
timeFrame: Cycle 1 (28 Days)
measure: Number of Participants with Treatment Emergent Adverse Events (TEAEs) and lab abnormalities (Phase 1)
timeFrame: From baseline until end of study treatment or study completion (approximately 2 years)
measure: Determine the Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RP2D) (Phase 1)
timeFrame: Approximately 16 months
measure: Objective Response Rate (ORR) (Phase 2)
timeFrame: From baseline through disease progression or study completion (approximately 2 years)
Secondary outcomes:
measure: Objective Response Rate (ORR) (Phase 1)
timeFrame: From baseline through disease progression or study completion (approximately 2 years)
measure: Duration of response (DOR) (Phase 1 and Phase 2)
timeFrame: From baseline through time to event on study or study completion (approximately 2 years)
measure: Progression Free Survival (PFS) (Phase 1 and Phase 2)
timeFrame: From baseline through time to event on study or study completion (approximately 2 years)
measure: Overall Survival (OS) (Phase 1 and Phase 2)
timeFrame: Approximately 76 months
measure: Disease control rate (DCR) (Phase 1 and Phase 2)
timeFrame: From baseline through disease progression or study completion (approximately 2 years)
measure: Clinical benefit rate (CBR) (Phase 1 and Phase 2)
timeFrame: From baseline through disease progression or study completion (approximately 2 years)
measure: PK Parameters: Maximum plasma concentration (Cmax) (Phase 1)
timeFrame: Day 1 and Day 15 of Cycle 1 (each cycle is 28 days)
measure: PK Parameters: Time to maximum plasma concentration (Tmax) (Phase 1)
timeFrame: Day 1 and Day 15 of Cycle 1 (each cycle is 28 days)
measure: PK Parameters: Elimination half-life (t1/2) (Phase 1)
timeFrame: Day 1 and Day 15 of Cycle 1 (each cycle is 28 days)
measure: PK Parameters: Area under the plasma concentration-time curve from time 0 to last measurable concentration (AUC 0-last) (Phase 1)
timeFrame: Day 1 and Day 15 of Cycle 1 (each cycle is 28 days)
measure: Determination of RP2D (Phase 2)
timeFrame: Approximately 16 months
measure: Number of Participants with Treatment Emergent Adverse Events (TEAEs) and lab abnormalities (Phase 2)
timeFrame: From baseline until end of study treatment or study completion (approximately 2 years)
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Avenzo Therapeutics Recruiting Site
state: California
city: New Haven
country: United States
facility: Avenzo Therapeutics Recruiting Site
state: Connecticut
city: Boston
country: United States
facility: Avenzo Therapeutics Recruiting Site
state: Massachusetts
city: New York
country: United States
facility: Avenzo Therapeutics Recruiting Site
state: New York
city: Cleveland
country: United States
facility: Avenzo Therapeutics Recruiting Site
state: Ohio
city: Houston
country: United States
facility: Avenzo Therapeutics Recruiting Site
state: Texas
city: San Antonio
country: United States
facility: Avenzo Therapeutics Recruiting Site
state: Texas
city: Fairfax
country: United States
facility: Avenzo Therapeutics Recruiting Site
state: Virginia
Study officials:
References: