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).
調査の概要
詳細な説明
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.
研究の種類
入学 (推定)
段階
- フェーズ 1
連絡先と場所
研究連絡先
- 名前：Jiangjiang Lv
- 電話番号：+86-021-58585793
- メール：jiangjiang.lv@mabwell.com
研究場所
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Shanghai Municipality
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Shanghai、Shanghai Municipality、中国、200025
- 募集
- Shanghai Jiao Tong University School of Medicine, Ruijin Hospital
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コンタクト：
- Jianqing Mi, PhD
- 電話番号：+86-13524488296
- メール：jianqingmi@shsmu.edu.cn
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参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
Inclusion Criteria:
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Age 18 years or older at the time of signing the informed consent form; male or female.
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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.
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Life expectancy greater than 3 months.
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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.
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MM only: measurable disease at screening.
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Adequate hematologic function at screening:
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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:
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small-molecule targeted therapy within 4 weeks or 5 half-lives, whichever is shorter;
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antibody therapy within 3 weeks;
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cytotoxic chemotherapy, proteasome inhibitor therapy, or traditional Chinese medicine (including Chinese patent medicine) with an anticancer indication within 2 weeks;
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immunomodulatory agent within 1 week;
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chimeric antigen receptor T-cell (CAR-T) therapy within 3 months;
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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.
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：非ランダム化
- 介入モデル：順次割り当て
- マスキング：なし（オープンラベル）
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
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実験的：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. |
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実験的：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. |
この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Number of participants with dose-limiting toxicities (DLTs)
時間枠：From the first dose of Cycle 1 through Day 28 of Cycle 1 (each cycle is 28 days)
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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)
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Number of participants with treatment-emergent adverse events (TEAEs)
時間枠：From first dose through 28 days after the last dose, an average of 1 year
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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
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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Overall response rate (ORR)
時間枠：From first dose through end of treatment, an average of 1 year
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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
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Maximum observed serum concentration (Cmax) of 6MW5311
時間枠：Through study completion, an average of 1 year
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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
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Area under the serum concentration-time curve (AUC) of 6MW5311
時間枠：Through study completion, an average of 1 year
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Through study completion, an average of 1 year
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Time to maximum observed serum concentration (Tmax) of 6MW5311
時間枠：Through study completion, an average of 1 year
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Through study completion, an average of 1 year
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Terminal elimination half-life (t1/2) of 6MW5311
時間枠：Through study completion, an average of 1 year
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Through study completion, an average of 1 year
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Systemic clearance (CL) of 6MW5311
時間枠：Through study completion, an average of 1 year
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Through study completion, an average of 1 year
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Volume of distribution (V) of 6MW5311
時間枠：Through study completion, an average of 1 year
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Through study completion, an average of 1 year
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協力者と研究者
研究記録日
主要日程の研究
研究開始 (実際)
一次修了 (推定)
研究の完了 (推定)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
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