NCT06998407|RecruitingPhase 1FDA Drug

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

AVZO-023-1001

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

Avenzo Therapeutics, Inc.ClinicalTrials.gov

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1 other identifier

AVZO-023-1001

Study Type

interventional

Target

380

Locations

1 country

Sites

Timeline

RegisteredMay 2025

StartedAug 2025

CompletionAug 2030

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).

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

380

participants targeted

Target at P75+ for phase_1

Timeline

51mo left

Started Aug 2025

Longer than P75 for phase_1

Geographic Reach

1 country

14 active sites

Status

recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

5 years study duration

Study Progress14%

Aug 2025Aug 2030

First Submitted

Initial submission to the registry

May 22, 2025

Completed

9 days until next milestone

First Posted

Study publicly available on registry

May 31, 2025

Completed

3 months until next milestone

Study Start

First participant enrolled

August 20, 2025

Completed

3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 1, 2028

Expected

2 years until next milestone

Study Completion

Last participant's last visit for all outcomes

August 1, 2030

Last Updated

May 4, 2026

Status Verified

February 1, 2026

Enrollment Period

3 years

First QC Date

May 22, 2025

Last Update Submit

April 28, 2026

Conditions

HR+/HER2- Breast Cancer HR+, HER2-, Advanced Breast Cancer

Outcome Measures

Primary Outcomes (4)

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.
Cycle 1 (28 Days)
Number of Participants with Treatment Emergent Adverse Events (TEAEs) and lab abnormalities (Phase 1)
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)
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.
From baseline through disease progression or study completion (approximately 2 years)

Secondary Outcomes (12)

Objective Response Rate (ORR) (Phase 1)
From baseline through disease progression or study completion (approximately 2 years)
Duration of response (DOR) (Phase 1 and Phase 2)
From baseline through time to event on study or study completion (approximately 2 years)
Progression Free Survival (PFS) (Phase 1 and Phase 2)
From baseline through time to event on study or study completion (approximately 2 years)
Overall Survival (OS) (Phase 1 and Phase 2)
Approximately 76 months
Disease control rate (DCR) (Phase 1 and Phase 2)
From baseline through disease progression or study completion (approximately 2 years)
+7 more secondary outcomes

Study Arms (4)

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

EXPERIMENTAL

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

Drug: FulvestrantDrug: AVZO-023

Phase 1, combination (Parts 1B)

EXPERIMENTAL

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

Drug: AVZO-021Drug: FulvestrantDrug: AVZO-023

Phase 1, combination (Parts 1C)

EXPERIMENTAL

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

Drug: AVZO-021Drug: LetrozoleDrug: AVZO-023

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

EXPERIMENTAL

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

Drug: AVZO-021Drug: FulvestrantDrug: LetrozoleDrug: AVZO-023

Interventions

AVZO-021DRUG

AVZO-021 is an oral selective CDK2 inhibitor

Phase 1, combination (Parts 1B)Phase 1, combination (Parts 1C)Phase 2, combination (Cohorts 2A, 2B, 2C, and 2D)

FulvestrantDRUG

Antineoplastic agent, estrogen receptor antagonist

Also known as: Faslodex

Phase 1, combination (Parts 1B)Phase 1, monotherapy (Part 1A) and food effectPhase 2, combination (Cohorts 2A, 2B, 2C, and 2D)

LetrozoleDRUG

Antineoplastic agent, aromatase inhibitor

Also known as: Femara

Phase 1, combination (Parts 1C)Phase 2, combination (Cohorts 2A, 2B, 2C, and 2D)

AVZO-023DRUG

AVZO-023 is an oral selective CDK4 inhibitor

Phase 1, combination (Parts 1B)Phase 1, combination (Parts 1C)Phase 1, monotherapy (Part 1A) and food effectPhase 2, combination (Cohorts 2A, 2B, 2C, and 2D)

Eligibility Criteria

Age18 Years+

Sexall

Healthy VolunteersNo

Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

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
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

Contact the study team to confirm eligibility.