진행성 고형암 환자의 ARTS-021 연구
고형 종양 환자의 단일 제제 및 병용 요법에서 ARTS-021의 안전성, 내약성, 약동학, 약력학, MTD/RP2D 및 항종양 활성을 평가하기 위한 1/2상 인간 최초 연구
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).
연구 개요
상태
상세 설명
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.
연구 유형
등록 (추정된)
단계
- 2 단계
- 1단계
연락처 및 위치
연구 연락처
- 이름: Medical Information
- 전화번호: (858) 239-2944
- 이메일: ClinicalTrials@avenzotx.com
연구 장소
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Connecticut
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New Haven, Connecticut, 미국, 06520
- 모병
- Avenzo Therapeutics Recruiting Site
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연락하다:
- Avenzo Therapeutics
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Florida
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Sarasota, Florida, 미국, 34232
- 모병
- Avenzo Therapeutics Recruiting Site
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연락하다:
- Avenzo Therapeutics
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Tampa, Florida, 미국, 33612
- 모병
- Avenzo Therapeutics Recruiting Site
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연락하다:
- Avenzo Therapeutics
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New York
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Mineola, New York, 미국, 11501
- 모병
- Avenzo Therapeutics Recruiting Site
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연락하다:
- Avenzo Therapeutics
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New York, New York, 미국, 10016
- 모병
- Avenzo Therapeutics Recruiting Site
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연락하다:
- Avenzo Therapeutics
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Ohio
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Cleveland, Ohio, 미국, 44106
- 모병
- Avenzo Therapeutics Recruiting Site
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연락하다:
- Avenzo Therapeutics
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Oklahoma
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Oklahoma City, Oklahoma, 미국, 73117
- 모병
- Avenzo Therapeutics Recruiting Site
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연락하다:
- Avenzo Therapeutics
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Oregon
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Portland, Oregon, 미국, 97213
- 모병
- Avenzo Therapeutics Recruiting Site
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연락하다:
- Avenzo Therapeutics
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Pennsylvania
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Philadelphia, Pennsylvania, 미국, 19107
- 모병
- Avenzo Therapeutics Recruiting Site
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연락하다:
- Avenzo Therapeutics
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Texas
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Dallas, Texas, 미국, 75246
- 모병
- Avenzo Therapeutics Recruiting Site
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연락하다:
- Avenzo Therapeutics
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Virginia
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Fairfax, Virginia, 미국, 22031
- 모병
- Avenzo Therapeutics Recruiting Site
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연락하다:
- Avenzo Therapeutics
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New South Wales
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Macquarie University, New South Wales, 호주
- 모병
- Avenzo Therapeutics Recruiting Site
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연락하다:
- Avenzo Therapeutics
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Wollongong, New South Wales, 호주
- 모병
- Avenzo Therapeutics Recruiting Site
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연락하다:
- Avenzo Therapeutics
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참여기준
자격 기준
공부할 수 있는 나이
건강한 자원 봉사자를 받아들입니다
연구 대상 성별
설명
Key Inclusion Criteria:
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Male or female aged ≥18 years old at screening with Eastern Cooperative Oncology Group (ECOG) 0-1.
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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).
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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).
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Measurable disease as determined by RECIST version 1.1.
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Adequate bone marrow and organ function.
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Ability to swallow capsules or tablets.
Key Exclusion Criteria:
- 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.
공부 계획
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 치료
- 할당: 무작위화되지 않음
- 중재 모델: 순차적 할당
- 마스킹: 없음(오픈 라벨)
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
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실험적: Phase 1, monotherapy (Part 1A)
Escalating doses of once daily, oral AVZO-021 in 28-day cycles. |
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) |
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실험적: Phase 1, combination (Parts 1B and 1C)
Escalating doses of once daily, oral AVZO-021 in 28-day cycles starting at least 1 DL below the monotherapy MTD/RP2D dose in combination with: 1B1) fulvestrant 1B2) palbociclib plus either fulvestrant or letrozole 1B3) ribociclib plus either fulvestrant or letrozole 1B4) abemaciclib plus either fulvestrant or letrozole 1B5) sacituzumab govitecan-hziy 1C) carboplatin |
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) Antineoplastic agent, cyclin-dependent kinase 4/6 inhibitor
다른 이름들:
Antineoplastic agent, estrogen receptor antagonist
다른 이름들:
Antineoplastic agent, aromatase inhibitor
다른 이름들:
Antineoplastic CDK4/6 inhibitor
다른 이름들:
Antineoplastic CDK4/6 inhibitor
다른 이름들:
Alkylating agent Trop-2 antibody and topoisomerase inhibitor
다른 이름들:
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실험적: Phase 2, monotherapy (Part 2A)
Oral doses of AVZO-021 in 28-day cycles at the RP2D determined in Part 1A. |
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) |
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실험적: Phase 2, combination (Parts 2B and 2C)
Oral doses of AVZO-021 in 28-day cycles at the RP2D determined in Parts 1B/1C, in combination with: 2B1) fulvestrant 2B2) palbociclib plus either fulvestrant or letrozole 2B3) ribociclib plus either fulvestrant or letrozole 2B4) abemaciclib plus either fulvestrant or letrozole 2B5) sacituzumab govitecan-hziy 2C) carboplatin |
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) Antineoplastic agent, cyclin-dependent kinase 4/6 inhibitor
다른 이름들:
Antineoplastic agent, estrogen receptor antagonist
다른 이름들:
Antineoplastic agent, aromatase inhibitor
다른 이름들:
Antineoplastic CDK4/6 inhibitor
다른 이름들:
Antineoplastic CDK4/6 inhibitor
다른 이름들:
Alkylating agent Trop-2 antibody and topoisomerase inhibitor
다른 이름들:
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연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
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Occurrence of Dose Limiting Toxicities (DLTs) during the first cycle (Phase 1)
기간: 28 Days
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Number of participants with DLTs assessed for severity using CTCAE v5.0 criteria will be summarized by dose level. |
28 Days
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Number of Participants with Treatment Emergent Adverse Events (TEAEs) and lab abnormalities (Phase 1)
기간: Approximately 22 months
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To evaluate the type, incidence, severity, timing, seriousness, and relationship to study treatment of adverse events and any laboratory abnormalities summarized by dose level. |
Approximately 22 months
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Determination of Recommended Phase 2 Dose (RP2D) (Phase 1)
기간: Approximately 16 months
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RP2D for AVZO-021 is less than or the same as the maximum tolerated dose (MTD) as defined by the occurrence of DLTs and TEAEs calculated using isotonic regression. |
Approximately 16 months
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Objective Response Rate (ORR) (Phase 2)
기간: Approximately 52 months
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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. |
Approximately 52 months
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Progression Free Survival (PFS) (Phase 2)
기간: Approximately 52 months
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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. |
Approximately 52 months
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Overall Survival (OS) (Phase 2)
기간: Approximately 76 months
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Defined as the time from study drug treatment initiation to death from any cause. |
Approximately 76 months
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Duration of response (DOR) (Phase 2)
기간: Approximately 52 months
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Defined as the time from the first confirmed response to radiologic/objective progression. |
Approximately 52 months
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2차 결과 측정
결과 측정 |
기간 |
|---|---|
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PK 매개변수: 최대 혈장 농도(Cmax)(단독요법 및 병용요법)
기간: 주기 1일 1, 2, 8, 14, 15(각 주기는 28일)
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주기 1일 1, 2, 8, 14, 15(각 주기는 28일)
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PK 매개변수: 최대 혈장 농도까지의 시간(Tmax)(단독요법 및 병용요법)
기간: 주기 1일 1, 2, 8, 14, 15(각 주기는 28일)
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주기 1일 1, 2, 8, 14, 15(각 주기는 28일)
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PK 매개변수: 0시부터 마지막 측정 가능 농도(AUC 0-last)까지의 혈장 농도-시간 곡선 아래 면적(단독요법 및 병용요법)
기간: 주기 1일 1, 2, 8, 14, 15(각 주기는 28일)
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주기 1일 1, 2, 8, 14, 15(각 주기는 28일)
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PK 매개변수: 0시부터 마지막 측정 가능 농도(AUC 0-tau)까지의 혈장 농도-시간 곡선 아래 면적(단독요법 및 병용)
기간: 주기 1일 1, 2, 8, 14, 15(각 주기는 28일)
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주기 1일 1, 2, 8, 14, 15(각 주기는 28일)
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PK 매개변수: 정상 상태에서 관찰된 최소 혈장 농도(Cmin, ss)(단독요법 및 병용요법)
기간: 주기 1일 1, 2, 8, 14, 15(각 주기는 28일)
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주기 1일 1, 2, 8, 14, 15(각 주기는 28일)
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PK 매개변수: 축적 비율(Rac)(단독요법 및 병용)
기간: 주기 1일 1, 2, 8, 14, 15(각 주기는 28일)
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주기 1일 1, 2, 8, 14, 15(각 주기는 28일)
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PK 매개변수: 제거 반감기(t1/2)(단독요법 및 병용)
기간: 주기 1일 1, 2, 8, 14, 15(각 주기는 28일)
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주기 1일 1, 2, 8, 14, 15(각 주기는 28일)
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PK 매개변수: 겉보기 청소율(CL/F)(단독요법 및 병용요법)
기간: 주기 1일 1, 2, 8, 14, 15(각 주기는 28일)
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주기 1일 1, 2, 8, 14, 15(각 주기는 28일)
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PK 매개변수: 말기 단계 동안 겉보기 분포 용적(Vz/F)(단독요법 및 병용요법)
기간: 주기 1일 1, 2, 8, 14, 15(각 주기는 28일)
|
주기 1일 1, 2, 8, 14, 15(각 주기는 28일)
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AVZO-021의 PK에 대한 고지방 식사의 효과 평가(1상)
기간: 5 일
|
5 일
|
공동 작업자 및 조사자
연구 기록 날짜
연구 주요 날짜
연구 시작 (실제)
기본 완료 (추정된)
연구 완료 (추정된)
연구 등록 날짜
최초 제출
QC 기준을 충족하는 최초 제출
처음 게시됨 (실제)
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
QC 기준을 충족하는 마지막 업데이트 제출
마지막으로 확인됨
추가 정보
이 연구와 관련된 용어
추가 관련 MeSH 약관
- 비뇨생식기 질환
- 생식기 질환
- 내분비계 질환
- 비뇨생식기 신생물
- 부위별 신생물
- 신생물
- 여성 비뇨 생식기 질환
- 여성 비뇨 생식기 질환 및 임신 합병증
- 조직학적 유형에 따른 신생물
- 자궁 질환
- 생식기 질환, 여성
- 내분비샘 신생물
- 신생물, 선상 및 상피
- 난소 질환
- 부속기 질환
- 생식기 신생물, 여성
- 생식선 장애
- 피부병
- 유방 질환
- 암종
- 자궁 신생물
- 나팔관 질환
- 난소 신생물
- 피부 및 결합 조직 질환
- 암종, 난소 상피
- 유방 신생물
- 삼중 음성 유방 신생물
- 자궁내막 신생물
- 나팔관 신생물
- 호르몬
- 호르몬, 호르몬 대체제, 호르몬 길항제
- 유기 화학 물질
- 이종 사이 클릭 화합물, 1- 링
- 이종 사이 클릭 화합물
- Azoles
- 다 환식 화합물
- 조정 복합체
- 스테로이드
- 융합 링 화합물
- 니트릴 레스
- 에스트라 디올
- 에스트 렌스
- Estranes
- 에스트라 디올 선수
- 생식선 스테로이드 호르몬
- 생식선 호르몬
- 트리아 졸
- 레트로졸
- 풀베스트란트
- 카르보플라틴
- Abemaciclib
- ribociclib
- palbociclib
- Sacituzumab Govitecan
기타 연구 ID 번호
- AVZO-021-1001
개별 참가자 데이터(IPD) 계획
개별 참가자 데이터(IPD)를 공유할 계획입니까?
약물 및 장치 정보, 연구 문서
미국 FDA 규제 의약품 연구
미국 FDA 규제 기기 제품 연구
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