Phase 1 Study of 6MW5311 in Adults With Relapsed or Refractory Blood Cancers
A Phase 1, Safety, Pharmacokinetic, Immunogenicity, and Preliminary Efficacy Study of 6MW5311 in Relapsed/Refractory Acute Myeloid Leukemia (AML) Patients, in Chronic Myelomonocytic Leukemia (CMML) Patients and Multiple Myeloma (MM) Patients
To assess safety and tolerability at increasing dose levels of 6MW5311 in successive cohorts of participants with MM, AML and CMML in order to estimate the maximum tolerated dose (MTD) and select the recommended Phase 2 dose (RP2D) or the recommended expansion dose (RED).
연구 개요
상세 설명
This is a 2-part, open-label, multicenter, First-in-Human Phase 1 clinical trial consisting of dose escalation (Part 1) and dose expansion (Part 2). Part 1 will evaluate the safety and tolerability, immunogenicity, PK/PD, biomarker, and preliminary clinical activities of 6MW5311. Part 2 will select appropriate dose(s) for expansion based on preliminary efficacy, safety, immunogenicity, PK/PD, and biomarkers data from Part 1, and will further assess the safety, PK, biomarker, and efficacy of 6MW5311. Upon completion of the Phase 1 clinical trial and findings from non-clinical studies, the recommended expansion dose (RED) or recommended Phase 2 dose (RP2D) of 6MW5311 in patients with hematological malignancies will be determined.
연구 유형
등록 (추정된)
단계
- 1단계
연락처 및 위치
연구 연락처
- 이름: Jiangjiang Lv
- 전화번호: +86-021-58585793
- 이메일: jiangjiang.lv@mabwell.com
연구 장소
-
-
Shanghai Municipality
-
Shanghai, Shanghai Municipality, 중국, 200025
- 모병
- Shanghai Jiao Tong University School of Medicine, Ruijin Hospital
-
연락하다:
- Jianqing Mi, PhD
- 전화번호: +86-13524488296
- 이메일: jianqingmi@shsmu.edu.cn
-
-
참여기준
자격 기준
공부할 수 있는 나이
건강한 자원 봉사자를 받아들입니다
연구 대상 성별
설명
Inclusion Criteria:
-
Age 18 years or older at the time of signing the informed consent form; male or female.
-
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 for the dose-escalation part, or 0 to 2 for the dose-expansion part.
-
Life expectancy greater than 3 months.
-
Multiple myeloma (MM): histologically and/or cytologically confirmed MM per International Myeloma Working Group (IMWG) 2016 criteria, with at least 3 prior lines of MM therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.
- Chronic myelomonocytic leukemia (CMML): morphologically confirmed by bone marrow examination per World Health Organization (WHO) 2016 classification, with relapsed disease or failure of prior therapy.
- Acute myeloid leukemia (AML; dose-expansion part only): morphologically confirmed acute myelomonocytic leukemia or acute monocytic leukemia per WHO 2016 classification, meeting the protocol definition of relapsed or refractory AML.
-
MM only: measurable disease at screening.
-
Adequate hematologic function at screening:
-
Able to understand and comply with the protocol requirements, willing to participate in the clinical study, and able to provide written informed consent.
Exclusion Criteria:
- 1. AML and CMML only: any other anticancer therapy within 2 weeks before the first dose of study drug.
MM only: prior anticancer therapy within the following intervals before the first dose of study drug:
-
small-molecule targeted therapy within 4 weeks or 5 half-lives, whichever is shorter;
-
antibody therapy within 3 weeks;
-
cytotoxic chemotherapy, proteasome inhibitor therapy, or traditional Chinese medicine (including Chinese patent medicine) with an anticancer indication within 2 weeks;
-
immunomodulatory agent within 1 week;
-
chimeric antigen receptor T-cell (CAR-T) therapy within 3 months;
-
radiotherapy within 1 week. 2. Receipt of any other investigational drug within 4 weeks before the first dose of study drug.
3. Prior allogeneic stem cell transplant; or autologous stem cell transplant within 3 months before the first dose of study drug.
4. Planned stem cell transplant during the study. 5. Prior treatment with a LILRB4-targeted therapy.
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 |
|---|---|
|
실험적: Part 1 - Dose Escalation (6MW5311)
A modified 3+3 design with accelerated titration will be used to evaluate planned dose levels. |
A bispecific T cell engager (TCE) antibody: bivalent binding to LILRB4 on tumor cells and monovalent binding to CD3 on T cells. |
|
실험적: Part 2 - Dose Expansion (6MW5311)
Participants with chronic myelomonocytic leukemia (CMML), multiple myeloma (MM), or relapsed or refractory acute myeloid leukemia (AML; acute myelomonocytic or monocytic subtypes) will receive 6MW5311 at the dose level(s) selected by the Safety Review Committee from Part 1. |
A bispecific T cell engager (TCE) antibody: bivalent binding to LILRB4 on tumor cells and monovalent binding to CD3 on T cells. |
연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
|
Number of participants with dose-limiting toxicities (DLTs)
기간: From the first dose of Cycle 1 through Day 28 of Cycle 1 (each cycle is 28 days)
|
DLTs are adverse events considered related to 6MW5311 (definitely, probably, or possibly related) that occur during the dose-limiting toxicity observation period (first 28 days after the first dose of Cycle 1). DLTs are defined per the protocol and graded per the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 6.0. |
From the first dose of Cycle 1 through Day 28 of Cycle 1 (each cycle is 28 days)
|
|
Number of participants with treatment-emergent adverse events (TEAEs)
기간: From first dose through 28 days after the last dose, an average of 1 year
|
TEAEs will be graded per NCI CTCAE version 6.0 and coded by system organ class and preferred term. |
From first dose through 28 days after the last dose, an average of 1 year
|
2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
|
Overall response rate (ORR)
기간: From first dose through end of treatment, an average of 1 year
|
ORR is the proportion of participants with a confirmed response. For multiple myeloma: the sum of confirmed stringent complete response, complete response, very good partial response, and partial response per International Myeloma Working Group (IMWG) 2016 criteria. For acute myeloid leukemia: the sum of confirmed complete response, complete remission with incomplete hematologic recovery, complete remission with partial hematologic recovery, morphologic leukemia-free state, and partial response per European LeukemiaNet (ELN) 2022 criteria. For chronic myelomonocytic leukemia: the sum of confirmed complete response, marrow response, partial response, and clinical benefit per the international MDS/MPN working group criteria. |
From first dose through end of treatment, an average of 1 year
|
|
Maximum observed serum concentration (Cmax) of 6MW5311
기간: Through study completion, an average of 1 year
|
Cmax is the maximum observed serum concentration of 6MW5311, read directly from the individual serum concentration-time profile after intravenous infusion. |
Through study completion, an average of 1 year
|
|
Area under the serum concentration-time curve (AUC) of 6MW5311
기간: Through study completion, an average of 1 year
|
Through study completion, an average of 1 year
|
|
|
Time to maximum observed serum concentration (Tmax) of 6MW5311
기간: Through study completion, an average of 1 year
|
Through study completion, an average of 1 year
|
|
|
Terminal elimination half-life (t1/2) of 6MW5311
기간: Through study completion, an average of 1 year
|
Through study completion, an average of 1 year
|
|
|
Systemic clearance (CL) of 6MW5311
기간: Through study completion, an average of 1 year
|
Through study completion, an average of 1 year
|
|
|
Volume of distribution (V) of 6MW5311
기간: Through study completion, an average of 1 year
|
Through study completion, an average of 1 year
|
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
기타 연구 ID 번호
- 6MW5311-CP101
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
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. .