KRAS G12D-specific Immune Effector Cells Targeting KRAS G12D-positive Solid Tumors
KRAS G12D-specific Engineered Immune Effectors (EIE) Targeting High-risk Tumors With KRAS G12D Mutation
The purpose of this study is to assess the feasibility, safety and efficacy of KRAS G12D-specific engineered immune effector (EIE) therapy in patients with advanced, KRAS G12D-positive malignancies. Another goal of the study is to characterize the function, expansion and persistence of KRAS G12D-specific effector cells in treated patients.
調査の概要
状態
状態
条件
条件
介入・治療
介入・治療
詳細な説明
Important Regulatory Notice:
This trial record is only for global academic information registration on ClinicalTrials.gov. Neither the sponsor Beijing Meikang Jimian Biotechnology Co., Ltd. nor collaborator Shenzhen Geno-Immune Medical Institute has obtained NMPA clinical trial approval or clinical technology filing permission to carry out interventional cell therapy trials in mainland China.
ClinicalTrials.gov registration alone does not represent legal approval by Chinese health and drug regulatory authorities.
KRAS G12D mutation is one of the most frequent oncogenic drivers in human malignancies including pancreatic ductal adenocarcinoma, colorectal cancer, non-small cell lung cancer and other advanced solid tumors. Patients with metastatic KRAS G12D mutated tumors generally have poor prognosis; after failure of standard chemotherapy, targeted therapy and checkpoint immunotherapy, effective salvage treatment options remain very limited, and overall survival is unsatisfactory. Conventional chemotherapy and existing targeted agents cannot achieve durable tumor control for large proportions of these patients.
The somatic KRAS G12D neoantigen is tumor-specific, absent in normal human tissues, and critical for maintaining malignant phenotypes, which makes it an attractive target for adoptive cell immunotherapy. This trial investigates autologous KRAS G12D-specific EIE therapy. Peripheral blood mononuclear cells (PBMCs) will be collected via leukapheresis and stimulated with autologous dendritic cells primed with KRAS G12D-specific immunogenic peptides. Manufactured EIE products will be phenotypically profiled for CD8+, CD4+ and CD56+ lymphocyte subsets together with antigen specific reactivity. This phase 1/2 study aims to evaluate safety, manufacturing feasibility and preliminary anti-tumor efficacy of autologous KRAS G12D-specific EIEs in subjects with KRAS G12D-positive tumors.
研究の種類
研究の種類
入学 (推定)
入学
段階
段階
- 適用できない
連絡先と場所
研究連絡先
研究連絡先
- 名前：Lung-Ji Chang, PhD
- 電話番号：+86 13671121909
- メール：c@mkgimi.com
研究場所
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-
Guangdong
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Shenzhen、Guangdong、中国、518000
- Shenzhen Geno-immune Medical Institute
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コンタクト：
- Lung-Ji Chang, PhD
- 電話番号：+86 13671121909
- メール：c@mkgimi.com
-
-
参加基準
適格基準
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:
- Abilities to understand and the willingness to provide written informed consent;
- ≥ 18 and ≤ 75 years old;
- Histologically confirmed recurrent, refractory or metastatic advanced malignancies with documented KRAS G12D somatic mutation and measurable lesions by RECIST v1.1; patients have progressed after at least one line of standard of care systemic therapy for their malignancy. At time of leukapheresis, patients are either off dexamethasone or receiving dexamethasone ≤ 4 mg/day;
- ECOG performance status 0-2 (or Karnofsky performance score ≥ 60);
- Life expectancy >3 months;
- Satisfactory bone marrow, liver and kidney functions as defined by the following: absolute neutrophile count ≥ 1500/mm^3; hemoglobin > 10 g/dL; platelets > 100000 /mm^3; Bilirubin < 1.5×ULN; alanine aminotransferase (ALT) or aspartate aminotransferase (AST) < 2.5×ULN; creatinine < 1.5×ULN;
- Peripheral blood absolute lymphocyte count must be above 0.8×10^9/L;
- Satisfactory heart functions;
- Must be willing to follow the instructions of doctors;
- Women of reproductive potential (between 15 and 49 years old) must have a negative pregnancy test within 7 days of study start. Male and female patients of reproductive potential must agree to use birth control during the study and 3 months post study.
Exclusion Criteria:
- Receipt of KRAS G12D based therapy within 8 weeks prior to study entry;
- HIV positive;
- Tuberculosis infection not under control;
- History of autoimmune disease, or other diseases requiring long-term administration of steroids or immunosuppressive therapies;
- History of allergic disease, or allergy to immune cells or study product;
- Patients already actively enrolled in other immune cell clinical study;
- Presence of untreated or actively progressing central nervous system metastases not locally controlled;
- Patients, in the opinion of investigators, may not be eligible or not able to comply with the study.
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：なし
- 介入モデル：単一グループの割り当て
- マスキング：なし（オープンラベル）
アーム数
武器と介入
参加者グループ / アーム参加者グループ / アーム |
介入・治療介入・治療 |
|---|---|
|
実験的：KRAS G12D-EIEs
Autologous KRAS G12D-specific engineered immune effectors (EIEs) |
1 to 2 infusions, once a week, for 1x10^5~1x10^7 EIEs/kg via intravenous injection each time |
この研究は何を測定していますか？
主要な結果の測定
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Percentage of adverse effects after KRAS G12D-EIE injection
時間枠：up to one month
|
To assess the safety of autologous KRAS G12D-EIEs in vivo. The percentage of patients who have adverse effects will be evaluated by using the NCI CTCAE V4.0 criteria. |
up to one month
|
二次結果の測定
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Rate of successful KRAS G12D-EIE generation
時間枠：up to one month
|
The percentage of successful KRAS G12D-EIE generation, which are derived from subjects and pass the safety test after standard culture procedures, viable for at least one preparation, will be evaluated. |
up to one month
|
|
Ability of KRAS G12D-EIE cells to induce cancer-specific reactions
時間枠：: after 1 month from KRAS G12D-EIE cell infusion until 24 months after infusion
|
ELISPOT measurement of target-specific T cells in blood sample |
: after 1 month from KRAS G12D-EIE cell infusion until 24 months after infusion
|
|
Ability of KRAS G12D-EIE cells inducing tumor reduction
時間枠：after 1 month from KRAS G12D-EIE cell infusion until 24 months after infusion
|
Objective response (complete response (CR) + partial response (PR)) will be assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria. CR is disappearance of all target lesions. Any pathological lesions (whether target or non-target) must have reduction in short axis to <10 mm. Partial response is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. |
after 1 month from KRAS G12D-EIE cell infusion until 24 months after infusion
|
協力者と研究者
研究記録日
主要日程の研究
研究開始 (推定)
研究開始
一次修了 (推定)
一次修了
研究の完了 (推定)
研究の完了
試験登録日
最初に提出
最初に提出
QC基準を満たした最初の提出物
QC基準を満たした最初の提出物
最初の投稿 (実際)
最初の投稿
学習記録の更新
投稿された最後の更新 (実際)
投稿された最後の更新
QC基準を満たした最後の更新が送信されました
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
最終確認日
詳しくは
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