이 페이지는 자동 번역되었으며 번역의 정확성을 보장하지 않습니다. 참조하십시오 영문판 원본 텍스트의 경우.

재발성 또는 불응성 B세포 비호지킨 림프종 환자에서 TNB-486에 대한 연구

2026년 9월 24일 업데이트: AstraZeneca

재발성 또는 불응성 B세포 비호지킨 림프종 대상자에서 CD19를 표적으로 하는 이중특이성 항체 TNB-486의 다기관, 1상, 공개 라벨, 용량 증량 및 확장 연구

This phase 1 study will investigate the safety, tolerability, pharmacokinetic, pharmacodynamic, and clinical activity of AZD0486, a CD19 x CD3 T-cell engaging bispecific antibody, in subjects with B-cell non-Hodgkin lymphoma (B-NHL).

연구 개요

상태

모집하지 않고 적극적으로

정황

개입 / 치료

상세 설명

This dose escalation and optimization study, is evaluating the safety, tolerability, PK, PD and clinical activity of AZD0486 monotherapy.

연구 유형

중재적

등록 (실제)

226

단계

  • 1단계

연락처 및 위치

이 섹션에서는 연구를 수행하는 사람들의 연락처 정보와 이 연구가 수행되는 장소에 대한 정보를 제공합니다.

연구 장소

  • 대만
      • Kaohsiung City, 대만, 833401
        • Research Site
      • Kweishan, 대만, 333
        • Research Site
      • Tainan, 대만, 704
        • Research Site
      • Taipei, 대만, 10002
        • Research Site
  • 대한민국
      • Seoul, 대한민국, 03080
        • Research Site
      • Seoul, 대한민국, 05505
        • Research Site
      • Seoul, 대한민국, 06351
        • Research Site
      • Seoul, 대한민국, 06591
        • Research Site
      • Seoul, 대한민국, 120-752
        • Research Site
  • 미국
    • Florida
      • Tampa, Florida, 미국, 33612
        • Research Site
    • Kentucky
      • Louisville, Kentucky, 미국, 40207
        • Research Site
    • New Jersey
      • New Brunswick, New Jersey, 미국, 08901
        • Research Site
    • North Carolina
      • Charlotte, North Carolina, 미국, 28204
        • Research Site
    • Ohio
      • Columbus, Ohio, 미국, 43210
        • Research Site
    • Pennsylvania
      • Pittsburgh, Pennsylvania, 미국, 15237
        • Research Site
    • Texas
      • Austin, Texas, 미국, 78704
        • Research Site
      • Houston, Texas, 미국, 77030
        • Research Site
    • Wisconsin
      • Milwaukee, Wisconsin, 미국, 53226
        • Research Site
  • 일본
      • Chūōku, 일본, 104-0045
        • Research Site
      • Kōtoku, 일본, 135-8550
        • Research Site
      • Nagoya, 일본, 460-0001
        • Research Site
      • Yamagata, 일본, 990-9585
        • Research Site
  • 호주
      • Heidelberg, 호주, 3084
        • Research Site
      • Hobart, 호주, 7000
        • Research Site
      • Melbourne, 호주, 3004
        • Research Site

참여기준

연구원은 적격성 기준이라는 특정 설명에 맞는 사람을 찾습니다. 이러한 기준의 몇 가지 예는 개인의 일반적인 건강 상태 또는 이전 치료입니다.

자격 기준

공부할 수 있는 나이

18년 (성인, 고령자)

건강한 자원 봉사자를 받아들입니다

아니

연구 대상 성별

모두

설명

Inclusion Criteria:

  • Biopsy proven B-NHL, including DLBCL, HGBL, or FL.
  • Relapsed/refractory cohorts:

In order to be eligible subjects must have received at least 2 prior lines of therapy and not be candidates for treatment regimens known to provide clinical benefit in B-NHL. CAR T-naive subjects are allowed if they have declined, are considered ineligible for, or do not have timely access to CAR T cell therapies.

  • 1L FL cohorts: Subject has biopsy-proven FL Grade 1-3a per WHO 2016 classification, Stage II-IV, FL International Prognostic Index 2-5 that has not been treated with prior systemic lymphoma-directed therapy and requires initiation of treatment based on GELF criteria. Radiation to localized disease prior to study entry is allowed if >14 days from first dose.
  • All Cohorts:

Subject has an Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2.

  • Subject must have adequate liver, bone marrow and kidney function (eGFR ≥ 50 mL/min).
  • Subject must have locally confirmed CD19 positivity (must be documented after time of progression from last CD19-targeted therapy, if received)
  • Subject must have at least 1 measurable disease site
  • Subject must have ANC >/= 1000/mm3, platelets >/= 50,000 mm3, hemoglobin >/= 8.0 g/dL. Transfusion and/or growth factor are allowed but counts must be stable for at least 72 hours afterwards prior to screening
  • Subject must have a total bilirubin <1.5x ULN, AST/ALT < 3xULN

Exclusion Criteria:

  • Subject has been diagnosed with or treated for another malignancy whose natural history or treatment may interfere with the safety or efficacy assessment of the investigational regimen.
  • Subject has active central nervous system (CNS) involvement by their B-NHL. --Subjects may be eligible with a distant history of CNS involvement that has been adequately treated with no evidence of recurrence within last 6 months from screening.
  • Subject has a history of leukemic presentation of their B-NHL (>5,000 circulating lymphoma cells/uL in the peripheral blood).
  • Subject has history or presence of clinically significant CNS pathology
  • Subject has CNS involvement from active or history of autoimmune disease.
  • Subject received CD19 CAR T therapy within 3 months prior to first dose.
  • Subject experienced Grade ≥ 3 cytokine release syndrome (CRS) following prior T-cell engager (TCE) or CAR T-cell therapy.
  • Subject experienced Grade ≥ 2 neurotoxicity/immune effector cell-associated neurotoxicity syndrome (ICANS) following prior TCE or CAR T-cell therapy.
  • Subject has received a peripheral autologous stem cell transplant (SCT) within 12 weeks, or an allogeneic SCT within 1 year of the first dose of study drug treatment or has received an SCT and requires ongoing immunosuppressive therapy.
  • Subjects with human immunodeficiency virus (HIV) infection, or subjects with chronic or active infection with hepatitis B virus (HBV) or hepatitis C virus (HCV). HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial. Subjects with chronic HBV may be enrolled if the HBV viral load is undetectable on suppressive therapy, or if the subject has a documented cure. Subjects with HCV who have a documented cure may be enrolled.
  • Subject has a history of major cardiac abnormalities.
  • If female, subject must not be pregnant or breastfeeding.

공부 계획

이 섹션에서는 연구 설계 방법과 연구가 측정하는 내용을 포함하여 연구 계획에 대한 세부 정보를 제공합니다.

연구는 어떻게 설계됩니까?

디자인 세부사항

  • 주 목적: 치료
  • 할당: 해당 없음
  • 중재 모델: 순차적 할당
  • 마스킹: 없음(오픈 라벨)

무기와 개입

참가자 그룹 / 팔
개입 / 치료
실험적: AZD0486 Monotherapy Dose Escalation in Subjects with B-NHL

AZD0486 monotherapy will be administered intravenously on day 1 and 15 of 28 day cycles for a maximum of 2 years or until discontinuation criteria are met. Depending on cohort, subjects may receive priming or step-up dosing administered weekly during cycle 1 before reaching the target dose. Additional cohorts may be opened where subjects receive weekly dosing during Cycles 1-2. While on study, subjects will be monitored for safety and efficacy with periodic disease assessment with PET/CT. If subject achieves two consecutive CRs after completing C6, then they may be eligible for monthly dosing
의약품: AZD0486 IV

AZD0486 is a bispecific antibody targeting CD19 on tumor cells and CD3 on T-cells leading to T cell-mediated cytotoxicity of malignant B cells

다른 이름들:
  • TNB-486

연구는 무엇을 측정합니까?

주요 결과 측정

결과 측정
측정값 설명
기간
Incidence of subjects with Dose-limiting toxicities (DLT)
기간: 28 days

A DLT is defined as a TEAE that is not unequivocally due to the subject's underlying malignancy or other extraneous cause. DLT evaluable subjects are defined as those subjects who receive either the target dose of AZD0486 or priming dose(s) in any step-up dose schedule and are assessed for toxicities for the 28-day evaluation period.

The NCI-CTCAE version 5.0 will be used (except for CRS and NT). A DLT will be evaluated as Non-hematologic, Hematologic, Cytokine Release Syndrome (CRS), or neurotoxicity.
28 days
Incidence of subjects with adverse events (AEs) and/or serious adverse events (SAEs)
기간: From screening until 90 Days after end of treatment

The incidence, timing, seriousness, and relationship to study treatment of adverse events will be evaluated.
From screening until 90 Days after end of treatment
Maximum Observed Serum Concentration of AZD0486 (Cmax)
기간: 4 Weeks

The maximum observed serum concentration on a concentration time curve.
4 Weeks
Area under the concentration versus time curve from time zero to the last quantifiable time point prior to the next dose (AUClast)
기간: 4 Weeks

Area under the serum concentration-time curve from time zero to time of last measurable concentration.
4 Weeks
Apparent terminal half-life (t1/2) of AZD0486
기간: From screening until 90 Days after end of treatment

Terminal half-life (t1/2,) will be determined after infusion in Cycle 1 using non-compartmental methods.
From screening until 90 Days after end of treatment

2차 결과 측정

결과 측정
측정값 설명
기간
Anti-Lymphoma Activity by Objective Response Rate (ORR)
기간: 48 months

Objective response rate is defined as the proportion of subjects with a confirmed partial or complete response to treatment
48 months
Anti-Lymphoma Activity by Progression-Free Survival (PFS)
기간: 48 months

Progression-free survival time is defined as the time from the first dose of AZD0486 to progression or death, whichever occurs first
48 months
Anti-Lymphoma Activity by Duration of Objective Response (DOR)
기간: 48 months

The duration of objective response for a subject is defined as the time from the initial objective response to disease progression or death, whichever occurs first
48 months
Anti-Lymphoma Activity by Clinical Benefit Rate
기간: 48 months

Clinical benefit rate is defined as the proportion of subjects with a confirmed complete response, partial response or minor response, or stable disease for at least 24 weeks after responding to treatment
48 months

공동 작업자 및 조사자

여기에서 이 연구와 관련된 사람과 조직을 찾을 수 있습니다.

스폰서

AstraZeneca

수사관

  • 연구 책임자: David Sermer, MD, AstraZeneca

연구 기록 날짜

이 날짜는 ClinicalTrials.gov에 대한 연구 기록 및 요약 결과 제출의 진행 상황을 추적합니다. 연구 기록 및 보고된 결과는 공개 웹사이트에 게시되기 전에 특정 품질 관리 기준을 충족하는지 확인하기 위해 국립 의학 도서관(NLM)에서 검토합니다.

연구 주요 날짜

연구 시작 (실제)

2021년 3월 2일

기본 완료 (추정된)

2028년 6월 19일

연구 완료 (추정된)

2028년 6월 19일

연구 등록 날짜

최초 제출

2020년 10월 13일

QC 기준을 충족하는 최초 제출

2020년 10월 13일

처음 게시됨 (실제)

2020년 10월 20일

연구 기록 업데이트

마지막 업데이트 게시됨 (실제)

2026년 9월 25일

QC 기준을 충족하는 마지막 업데이트 제출

2026년 9월 24일

마지막으로 확인됨

2026년 9월 1일

추가 정보

이 연구와 관련된 용어

키워드

추가 관련 MeSH 약관

기타 연구 ID 번호

  • D7400C00006

개별 참가자 데이터(IPD) 계획

개별 참가자 데이터(IPD)를 공유할 계획입니까?

예

IPD 계획 설명

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

"Yes", indicates that AZ are accepting requests for IPD, but this does not mean all requests will be approved.

Supporting

IPD 공유 기간

AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA/PhRMA Data-Sharing Principles. For details of our timelines, please refer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Access Criteria:

IPD 공유 액세스 기준

When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. A Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.

약물 및 장치 정보, 연구 문서

미국 FDA 규제 의약품 연구

예

미국 FDA 규제 기기 제품 연구

아니

이 정보는 변경 없이 clinicaltrials.gov 웹사이트에서 직접 가져온 것입니다. 귀하의 연구 세부 정보를 변경, 제거 또는 업데이트하도록 요청하는 경우 register@clinicaltrials.gov. 문의하십시오. 변경 사항이 clinicaltrials.gov에 구현되는 즉시 저희 웹사이트에도 자동으로 업데이트됩니다. .

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