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
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 (NCT05867251). In Phase 1, the safety and tolerability of AVZO-023 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.
Arms & interventions
- DrugAVZO-021
AVZO-021 is an oral selective CDK2 inhibitor
- DrugFulvestrant
Antineoplastic agent, estrogen receptor antagonist
- DrugLetrozole
Antineoplastic agent, aromatase inhibitor
- DrugAVZO-023
AVZO-023 is an oral selective CDK4 inhibitor
Outcome measures
Primary
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.
Time frame: Cycle 1 (28 Days)
Number of Participants with Treatment Emergent Adverse Events (TEAEs) and lab abnormalities (Phase 1)
Time frame: From baseline until end of study treatment or study completion (approximately 2 years)
Determine the Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RP2D) (Phase 1)
Time frame: 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.
Time frame: From baseline through disease progression or study completion (approximately 2 years)
Secondary
Objective Response Rate (ORR) (Phase 1)
Time frame: From baseline through disease progression or study completion (approximately 2 years)
Duration of response (DOR) (Phase 1 and Phase 2)
Time frame: From baseline through time to event on study or study completion (approximately 2 years)
Progression Free Survival (PFS) (Phase 1 and Phase 2)
Time frame: From baseline through time to event on study or study completion (approximately 2 years)
Overall Survival (OS) (Phase 1 and Phase 2)
Time frame: Approximately 76 months
Disease control rate (DCR) (Phase 1 and Phase 2)
Time frame: From baseline through disease progression or study completion (approximately 2 years)
Clinical benefit rate (CBR) (Phase 1 and Phase 2)
Time frame: From baseline through disease progression or study completion (approximately 2 years)
PK Parameters: Maximum plasma concentration (Cmax) (Phase 1)
Time frame: Day 1 and Day 15 of Cycle 1 (each cycle is 28 days)
PK Parameters: Time to maximum plasma concentration (Tmax) (Phase 1)
Time frame: Day 1 and Day 15 of Cycle 1 (each cycle is 28 days)
PK Parameters: Elimination half-life (t1/2) (Phase 1)
Time frame: Day 1 and Day 15 of Cycle 1 (each cycle is 28 days)
PK Parameters: Area under the plasma concentration-time curve from time 0 to last measurable concentration (AUC 0-last) (Phase 1)
Time frame: Day 1 and Day 15 of Cycle 1 (each cycle is 28 days)
Determination of RP2D (Phase 2)
Time frame: Approximately 16 months
Number of Participants with Treatment Emergent Adverse Events (TEAEs) and lab abnormalities (Phase 2)
Time frame: From baseline until end of study treatment or study completion (approximately 2 years)
Eligibility criteria
Study locations (14)
Avenzo Therapeutics Recruiting Site
Los Angeles, California, 90025
Avenzo Therapeutics Recruiting Site
Los Angeles, California, 90095
Avenzo Therapeutics Recruiting Site
New Haven, Connecticut, 06519
Avenzo Therapeutics Recruiting Site
Orlando, Florida, 32827
Avenzo Therapeutics Recruiting Site
Sarasota, Florida, 34232
Avenzo Therapeutics Recruiting Site
Boston, Massachusetts, 02215
Avenzo Therapeutics Recruiting Site
New York, New York, 10016
Avenzo Therapeutics Recruiting Site
Cleveland, Ohio, 44106
Avenzo Therapeutics Recruiting Site
Columbus, Ohio, 43221
Avenzo Therapeutics Recruiting Site
Nashville, Tennessee, 37203
Avenzo Therapeutics Recruiting Site
Fort Worth, Texas, 76104
Avenzo Therapeutics Recruiting Site
Houston, Texas, 77030
Avenzo Therapeutics Recruiting Site
San Antonio, Texas, 78229
Avenzo Therapeutics Recruiting Site
Fairfax, Virginia, 22031