Recruiting

Phase 1

Phase 2

AVZO-023ORION-1: Study of AVZO-023 as a Single Agent and in Combination With AVZO-021, and/or Endocrine Therapy in Advanced Solid Tumors

Sponsor:

Avenzo Therapeutics, Inc.

Code:

NCT06998407

Conditions

HR+/HER2- Breast Cancer

HR+, HER2-, Advanced Breast Cancer

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

AVZO-021

Fulvestrant

Letrozole

AVZO-023

Study Details

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).

Conditions

HR+/HER2- Breast Cancer

HR+, HER2-, Advanced Breast Cancer

Study ID

NCT06998407

Start date

Aug 20, 2025

Status verified date

Feb, 2026

Completion date

Aug, 2030

Anticipated

Primary completion date

Aug, 2028

Anticipated

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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. Bone only disease is allowed in dose escalation.
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 any prior selective investigational 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. Patients who received radiation of >25% of bone marrow are excluded.
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
Confirmed loss of function mutation or deletion of Rb1 gene
Previous high-dose chemotherapy requiring stem cell rescue

Study Design

Enrollment

380 participants

Anticipated

Allocation

Non randomized

Intervention Model

Sequential

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Phase 1, monotherapy (Part 1A) and food effect

Escalating doses of twice daily, oral AVZO-023 in 28-day cycles, with addition of fulvestrant

experimental: Phase 1, combination (Parts 1B)

Escalating doses of twice daily, oral AVZO-023 in combination with once daily, oral AVZO-021 in 28-day cycles, with addition of fulvestrant

experimental: Phase 1, combination (Parts 1C)

Escalating doses of twice daily, oral AVZO-023 in combination with once daily, oral AVZO-021, with once daily, oral letrozole in 28-day cycles

experimental: Phase 2, combination (Cohorts 2A, 2B, 2C, and 2D)

Oral doses of AVZO-023 in 28-day cycles at the RP2D determined in Part 1B/1C, in combination with:

2A) letrozole

2B) fulvestrant

2C) AVZO-021 plus fulvestrant

2D) AVZO-021 plus letrozole

Interventions

AVZO-021

AVZO-021 is an oral selective CDK2 inhibitor

Fulvestrant

Antineoplastic agent, estrogen receptor antagonist

Letrozole

Antineoplastic agent, aromatase inhibitor

AVZO-023

AVZO-023 is an oral selective CDK4 inhibitor

Primary outcome measure

Occurrence of Dose Limiting Toxicities (DLTs) during the first cycle (Phase 1) [ 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) [ Time Frame: From baseline through disease progression or study completion (approximately 2 years) ]

Central Contacts and Locations

Central contacts

Medical Information

(858) 239-2944 ClinicalTrials@avenzotx.com

Locations