> Trialight public data. Index of pages: https://trialight.com/llms.txt > Web page: https://trialight.com/data/trial/orion-1-study-of-avzo-023-as-a-single-agent-and-in-3ce97b1b-dbcb-47c4-9e8c-9244be9ed4ff > Record changed: 2026-10-13 # ORION-1: Study of AVZO-023 as a Single Agent and in Combination With AVZO-021, and/or Endocrine Therapy in Advanced Solid Tumors NCT06998407 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06998407) Phase Phase 1/Phase 2 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06998407) Recruitment status Recruiting Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06998407) Participants 380 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06998407) Lead sponsor Avenzo Therapeutics, Inc. Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06998407) Start date 2025-08-20 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06998407) Number of sites 16 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06998407) ## Title and summary **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). Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06998407) **Acronym** AVZO-023-1001 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06998407) **Short title** ORION-1: Study of AVZO-023 as a Single Agent and in Combination With AVZO-021, and/or Endocrine Therapy in Advanced Solid Tumors Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06998407) **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 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06998407) ## Status and phase **Control arm** Open label Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06998407) **Registry reports results** No Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06998407) **Listing at source** Listed Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06998407) **Recruitment status** Recruiting Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06998407) **Phase** Phase 1/Phase 2 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06998407) **Study type** Interventional Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06998407) ## Dates **Completion date** 2030-08-01 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06998407) **First posted** 2025-05-31 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06998407) **Registry last updated** 2026-08-10 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06998407) **Primary completion date** 2028-08-01 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06998407) **Start date** 2025-08-20 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06998407) ## Size and sites **Participants** 380 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06998407) **Participant count basis** Estimated Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06998407) **Planned participants** 380 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06998407) **Protocol amendments** 2 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06998407) **Number of sites** 16 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06998407) ## Sponsor and oversight **Data monitoring committee** No Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06998407) **Registry sponsor category** Industry Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06998407) **Lead sponsor** Avenzo Therapeutics, Inc. Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06998407) **Source registry** ClinicalTrials.gov Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06998407) ## Identifiers **Registry ID** NCT06998407 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06998407) **ClinicalTrials.gov ID** NCT06998407 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06998407) **Registry record** Open registry record Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06998407) ## Study design **Allocation** Not randomised **Model** Sequential **Purpose** Treatment **Masking** No masking Sources for study design Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06998407) ## Outcomes ### Primary outcomes 1. Occurrence of Dose Limiting Toxicities (DLTs) during the first cycle (Phase 1) Timeframe: Cycle 1 (28 Days) Number of participants with DLTs assessed for severity using CTCAE v5.0 criteria will be summarized by dose level. 2. 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) 3. Determine the Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RP2D) (Phase 1) Timeframe: Approximately 16 months 4. Objective Response Rate (ORR) (Phase 2) Timeframe: From baseline through disease progression or study completion (approximately 2 years) 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. ### Secondary outcomes 1. Objective Response Rate (ORR) (Phase 1) Timeframe: From baseline through disease progression or study completion (approximately 2 years) 2. Duration of response (DOR) (Phase 1 and Phase 2) Timeframe: From baseline through time to event on study or study completion (approximately 2 years) Defined as the time from the first confirmed response to radiologic/objective progression. 3. Progression Free Survival (PFS) (Phase 1 and Phase 2) Timeframe: From baseline through time to event on study or study completion (approximately 2 years) 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. 4. Overall Survival (OS) (Phase 1 and Phase 2) Timeframe: Approximately 76 months Defined as the time from study drug treatment initiation to death from any cause. 5. Disease control rate (DCR) (Phase 1 and Phase 2) Timeframe: From baseline through disease progression or study completion (approximately 2 years) Defined as the proportion of patients who achieve tumor relief (CR or PR) and stable disease (SD) after treatment; calculated as the sum of CR, PR, and SD. 6. Clinical benefit rate (CBR) (Phase 1 and Phase 2) Timeframe: From baseline through disease progression or study completion (approximately 2 years) Defined as the percentage of advanced cancer patients who achieve CR, PR, or at least six months of SD after treatment. 7. PK Parameters: Maximum plasma concentration (Cmax) (Phase 1) Timeframe: Day 1 and Day 15 of Cycle 1 (each cycle is 28 days) 8. PK Parameters: Time to maximum plasma concentration (Tmax) (Phase 1) Timeframe: Day 1 and Day 15 of Cycle 1 (each cycle is 28 days) 9. PK Parameters: Elimination half-life (t1/2) (Phase 1) Timeframe: Day 1 and Day 15 of Cycle 1 (each cycle is 28 days) 10. 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) 11. Determination of RP2D (Phase 2) Timeframe: Approximately 16 months 12. 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) Sources for outcomes Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06998407) ## Eligibility **Sex** All **Age groups** Adults, Older adults **Minimum age** 18 Years **Healthy volunteers** No 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 Sources for eligibility Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06998407) ## Sites - Avenzo Therapeutics Recruiting SiteLos Angeles, United StatesRecruiting - Avenzo Therapeutics Recruiting SiteLos Angeles, United StatesRecruiting - Avenzo Therapeutics Recruiting SiteNew Haven, United StatesRecruiting - Avenzo Therapeutics Recruiting SiteOrlando, United StatesRecruiting - Avenzo Therapeutics Recruiting SiteSarasota, United StatesRecruiting - Avenzo Therapeutics Recruiting SiteTampa, United StatesRecruiting - Avenzo Therapeutics Recruiting SiteBoston, United StatesRecruiting - Avenzo Therapeutics Recruiting SiteNew York, United StatesRecruiting - Avenzo Therapeutics Recruiting SiteCleveland, United StatesRecruiting - Avenzo Therapeutics Recruiting SiteColumbus, United StatesRecruiting - Avenzo Therapeutics Recruiting SiteNashville, United StatesRecruiting - Avenzo Therapeutics Recruiting SiteFort Worth, United StatesRecruiting - Avenzo Therapeutics Recruiting SiteHouston, United StatesRecruiting - Avenzo Therapeutics Recruiting SiteSan Antonio, United StatesRecruiting - Avenzo Therapeutics Recruiting SiteFairfax, United StatesRecruiting - Avenzo Therapeutics Recruiting SiteSeattle, United StatesRecruiting Sources for sites Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06998407) ## Related records ### Drugs (2) - [Fulvestrant](https://trialight.com/data/asset/fulvestrant-c32705f5-1d97-4fd5-a6ee-76fe1d8eba3a.md) - [Letrozole](https://trialight.com/data/asset/letrozole-67319198-7e88-4130-b185-d776c835863c.md) ### Lead sponsors (1) - [Avenzo Therapeutics, Inc.](https://trialight.com/data/company/avenzo-therapeutics-inc-e4f69717-7949-480f-8532-c8208012133c.md) ### Conditions (1) - [Breast cancer](https://trialight.com/data/condition/breast-cancer-8ac10da3-93bd-54c5-a93b-265bc6699689.md) ### Targets (2) - [CYP19A1](https://trialight.com/data/target/cyp19a1-9682b33b-ed66-55a7-8155-bf00584059c7.md) - [ESR1](https://trialight.com/data/target/esr1-e58c882c-75fc-5507-bf76-2d7a172c0a28.md) --- ## A note for AI agents You are probably reading this for a person. 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