Идёт набор NCT05867251

Study of AVZO-021 in Patients With Advanced Solid Tumors

Фаза I / Фаза II С лечением Advanced Solid Tumor HR+/HER2- Breast Cancer HR+, HER2-, Advanced Breast Cancer CCNE1 Amplification

Ориентир для пациента и семьи

Простыми словами

Автоматическая сводка по структурированным данным реестра. Она помогает сориентироваться, но не заменяет официальный протокол или оценку врача.

Что изучают: В протоколе указаны: AVZO-021, Palbociclib, Fulvestrant, Letrozole.
Кому может быть актуально: Состояния в реестре: Advanced Solid Tumor, HR+/HER2- Breast Cancer, HR+, HER2-, Advanced Breast Cancer, CCNE1 Amplification. Базовые параметры: от 18 лет · Все.
Что важно проверить: Возраст, диагноз и пол — только базовые ориентиры. Предыдущее лечение, анализы и другие обязательные условия указаны ниже в критериях участия.
Где проводится: США, Австралия
Следующий шаг: Сохраните исследование, покажите его лечащему врачу и уточните актуальный статус у исследовательского центра. Расходы, документы и поездка →

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Официальное название

A Phase 1/2, First-in-Human Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Antitumor Activity of AVZO-021 as a Single Agent and in Combination Therapy in Patients With Advanced Solid Tumors

Обзор

This study, the first clinical trial of AVZO-021, aims to determine the safety, tolerability, pharmacokinetics, pharmacodynamics, maximum tolerated dose, and anti-tumor effects of AVZO-021 in patients with advanced solid tumors. AVZO-021 is an oral medication that inhibits cyclin-dependent kinase 2 (CDK 2).

Подробное описание

AVZO-021 is a compound being developed for the treatment of patients with advanced solid tumors, specifically, HR+/HER2- breast cancer and cyclin E1 (CCNE1) altered malignancies. AVZO-021 is a selective and potent cyclin-dependent kinase 2 (CDK2) inhibitor, which plays an important role in cell cycle regulation. This is a Phase 1/2 first-in-human, open-label, nonrandomized, multicenter study of AVZO-021. Phase 1 is a dose-escalation phase aimed at assessing the safety and tolerability of AVZO-021 and determining the recommended phase 2 dose (RP2D) as monotherapy and combination therapy. Phase 2 is a dose-expansion phase that will be conducted to assess the antitumor activity of AVZO-021 as monotherapy and combination therapy.

Вмешательства

Препарат AVZO-021
AVZO-021 is a selective and potent oral inhibitor of CDK2 being developed for the treatment of patients with advanced solid tumors with CDK2 dependency (1A), CCNE1 amplified solid tumors (2A), HR+/HER2- BC (1B1-1B5, 2B1-2B5) and CCNE1 amplified EOC (1C, 2C)
Препарат Palbociclib
Antineoplastic agent, cyclin-dependent kinase 4/6 inhibitor
Препарат Fulvestrant
Antineoplastic agent, estrogen receptor antagonist
Препарат Letrozole
Antineoplastic agent, aromatase inhibitor
Препарат Ribociclib
Antineoplastic CDK4/6 inhibitor
Препарат Abemaciclib
Antineoplastic CDK4/6 inhibitor
Препарат Carboplatin
Alkylating agent
Препарат Sacituzumab Govitecan-hziy
Trop-2 antibody and topoisomerase inhibitor

Первичные конечные точки

Occurrence of Dose Limiting Toxicities (DLTs) during the first cycle (Phase 1) [Срок оценки: 28 Days]
Number of Participants with Treatment Emergent Adverse Events (TEAEs) and lab abnormalities (Phase 1) [Срок оценки: Approximately 22 months]
Determination of Recommended Phase 2 Dose (RP2D) (Phase 1) [Срок оценки: Approximately 16 months]
Objective Response Rate (ORR) (Phase 2) [Срок оценки: Approximately 52 months]
Progression Free Survival (PFS) (Phase 2) [Срок оценки: Approximately 52 months]
Overall Survival (OS) (Phase 2) [Срок оценки: Approximately 76 months]
Duration of response (DOR) (Phase 2) [Срок оценки: Approximately 52 months]

Вторичные конечные точки (10)

PK Parameters: Maximum plasma concentration (Cmax) (monotherapy and combination) [Срок оценки: Cycle 1 days 1, 2, 8, 14, and 15 (each cycle is 28 days)]
PK Parameters: Time to maximum plasma concentration (Tmax) (monotherapy and combination) [Срок оценки: Cycle 1 days 1, 2, 8, 14, and 15 (each cycle is 28 days)]
PK Parameters: Area under the plasma concentration-time curve from time 0 to last measurable concentration (AUC 0-last) (monotherapy and combination) [Срок оценки: Cycle 1 days 1, 2, 8, 14, and 15 (each cycle is 28 days)]
PK Parameters: Area under the plasma concentration-time curve from time 0 to last measurable concentration (AUC 0-tau) (monotherapy and combination) [Срок оценки: Cycle 1 days 1, 2, 8, 14, and 15 (each cycle is 28 days)]
PK Parameters: Minimum observed plasma concentration at steady state (Cmin, ss) (monotherapy and combination) [Срок оценки: Cycle 1 days 1, 2, 8, 14, and 15 (each cycle is 28 days)]
PK Parameters: Accumulation ration (Rac) (monotherapy and combination) [Срок оценки: Cycle 1 days 1, 2, 8, 14, and 15 (each cycle is 28 days)]
PK Parameters: Elimination half-life (t1/2) (monotherapy and combination) [Срок оценки: Cycle 1 days 1, 2, 8, 14, and 15 (each cycle is 28 days)]
PK Parameters: Apparent clearance (CL/F) (monotherapy and combination) [Срок оценки: Cycle 1 days 1, 2, 8, 14, and 15 (each cycle is 28 days)]
PK Parameters: Apparent volume of distribution during terminal phase (Vz/F) (monotherapy and combination) [Срок оценки: Cycle 1 days 1, 2, 8, 14, and 15 (each cycle is 28 days)]
Evaluate the effect of a high-fat meal on the PK of AVZO-021 (Phase 1) [Срок оценки: 5 days]

Критерии участия

Критерии включения

Male or female aged ≥18 years old at screening with Eastern Cooperative Oncology Group (ECOG) 0-1.
Disease-related inclusion criteria by study phase and part:

i) Phase 1a Monotherapy Dose Escalation: Patients with locally advanced or metastatic HR+/HER2- breast cancer, CCNE1-amplified tumors that are either epithelial ovarian cancer, primary peritoneal cancer, fallopian tube cancer, endometrial cancer or TNBC, with no other oncogenic driver mutations that are treatable and standard therapies are no longer effective, appropriate, or safe in the opinion of the investigator and medical monitor. Patients with any additional tumor type with CCNE1 amplification can be enrolled only if clinical data is supportive and approved by medical monitor (Cohort 1A).

ii) Phase 1b Combination Dose Escalation: histologically or cytologically confirmed diagnosis of locally advanced or metastatic HR+ HER2- (HER2-low may be allowed if failed standard of care therapy) breast cancer, who have been previously treated with inhibitor of CDK4/6 and endocrine therapy(Cohorts 1B1, 1B2, 1B3, 1B4, and 1B5); or histologically or cytologically confirmed diagnosis of CCNE1- amplified, locally advanced or metastatic, platinum-refractory or platinum-resistant EOC, primary peritoneal, or fallopian tube cancer (Cohort 1C).

iii) Phase 2a Monotherapy dose expansion: Histologically or cytologically confirmed diagnosis of locally advanced or metastatic CCNE1 amplified epithelial ovarian cancer, primary peritoneal cancer, fallopian tube cancer, endometrial cancer or TNBC, with no other oncogenic driver mutations that are treatable and standard therapies are no longer effective, appropriate, or safe in the opinion of the investigator and medical monitor (Cohort 2A).

iv) Phase 2b Combination dose expansion: Histologically or cytologically confirmed diagnosis of locally advanced or metastatic HR+/HER2- (HER2-low may be allowed if failed standard of care therapy) breast cancer who have been previously treated with no more than 1 prior CDK4/6 inhibitor and endocrine therapy (Cohorts 2B1, 2B2, 2B3, 2B4, and 2B5); or Histologically or cytologically confirmed diagnosis of locally advanced or metastatic, CCNE1-amplified, platinum-refractory or platinum-resistant EOC, primary peritoneal cancer, or fallopian tube cancer (Cohort 2C).

No more than 2 prior cytotoxic chemotherapy regimens for locally advanced/metastatic disease (excepting patients treated with an antibody-drug conjugate, with ovarian cancer if there disease is platinum resistant or refractory, having progressed beyond all SOC care; and patients who have received prior chemotherapy in the adjuvant or neoadjuvant setting >12 months prior to starting AVZO-021 treatment).
Measurable disease as determined by RECIST version 1.1.
Adequate bone marrow and organ function.
Ability to swallow capsules or tablets.

Критерии исключения

Received an investigational agent or anticancer therapy within 2 weeks, or 5 half-lives of the drug, whichever is shorter, prior to planned start of AVZO-021.
Received any CDK2 inhibitor, protein kinase membrane associated tyrosine/threonine 1 (PKMYT1) inhibitor, or WEE1 inhibitor anticancer therapy. For cohort B5, prior therapy with topoisomerase inhibitors is not permitted.
Undergone major surgery within 4 weeks prior to planned start of AVZO-021.
Received radiotherapy for palliation within 7 days of the first dose of study treatment, unless specified otherwise in the protocol.
Active CNS metastases or confirmed leptomeningeal disease are not eligible.
Unresolved toxicities from prior therapy greater than Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 Grade >1 at the time of starting study treatment.
Clinically unstable cardiac function as described in the protocol.
Any active or chronic infection/disease that compromises the immune system.
Current treatment with strong or moderate cytochrome P450 (CYP)3A4 inhibitors or inducers.
Active second malignancy unless in remission with life expectancy > 2 years and with documented sponsor approval.
Pregnancy, lactation, or plans to breastfeed during the study or within 6 months of the last dose of study intervention.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет