Health TrialsbyHealthPanel

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

ConditionsHR+/HER2- Breast CancerHR+, HER2-, Advanced Breast Cancer
Trial statusRecruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorAvenzo Therapeutics, Inc.

About this trial

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).

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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

Disqualifiers

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

Trial design

Design model

Sequential

Treatments tested in this trial

  • AVZO-021

    Drug

    AVZO-021 is an oral selective CDK2 inhibitor

  • Fulvestrant

    Drug

    Antineoplastic agent, estrogen receptor antagonist

  • Letrozole

    Drug

    Antineoplastic agent, aromatase inhibitor

  • AVZO-023

    Drug

    AVZO-023 is an oral selective CDK4 inhibitor

Treatment groups

380 Participants
are divided into 4 treatment groups
Group A: Phase 1, monotherapy (Part 1A) and food effectExperimental treatment 2 interventions
Group B: Phase 1, combination (Parts 1B)Experimental treatment 3 interventions
Group C: Phase 1, combination (Parts 1C)Experimental treatment 3 interventions
Group D: Phase 2, combination (Cohorts 2A, 2B, 2C, and 2D)Experimental treatment 4 interventions

Trial outcomes

Primary outcomes

1

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)
2

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)
3

Determine the Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RP2D) (Phase 1)

Time frame
Approximately 16 months
4

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 outcomes

1

Objective Response Rate (ORR) (Phase 1)

Time frame
From baseline through disease progression or study completion (approximately 2 years)
2

Duration of response (DOR) (Phase 1 and Phase 2)

Defined as the time from the first confirmed response to radiologic/objective progression.

Time frame
From baseline through time to event on study or study completion (approximately 2 years)
3

Progression Free Survival (PFS) (Phase 1 and Phase 2)

Defined as the time from study drug treatment to death or disease progression, as determined by the investigator by radiographic disease assessment according to RECIST v1.1.

Time frame
From baseline through time to event on study or study completion (approximately 2 years)
4

Overall Survival (OS) (Phase 1 and Phase 2)

Defined as the time from study drug treatment initiation to death from any cause.

Time frame
Approximately 76 months

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Avenzo Therapeutics, Inc.

Lead sponsor

Source ClinicalTrials.gov
Apply now