KXV01 Injection in Patients With Advanced Solid Tumor (Including Osteosarcoma and Sarcoma)
A Phase I Clinical Study on the Safety, Tolerability, and Efficacy of KXV01 Injection in Patients With Advanced Solid Tumor (Including Osteosarcoma and Sarcoma)
調査の概要
詳細な説明
In recent years, the field has found that patient-specific anti-tumor treatment technologies have increasingly significant clinical application prospects and clinical value. Patient-specific anti-tumor in vivo TCR gene therapy is an advanced therapeutic strategy that can specifically recognize tumor neoantigens. This strategy is not restricted by patients' HLA typing nor by the type of indication.
This investigator-initiated clinical study aims to evaluate KXV01 TCR Lentinvivo, the third-generation self-inactivating lentiviral vector that carries patient-derived personalized tumor reactive TCR, in patients with advanced solid tumors. The study employs a BOIN design to assess safety, tolerability, and preliminary efficacy.
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:Weichi Zhou
- 電話番号:+86-18994103369
- メール:zhouwc@tcrximmune.cn
研究場所
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Shanghai、中国、200233
- 募集
- Shanghai Sixth People's Hospital Affiliated to Shanghai JiaoTong University
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コンタクト:
- HaiYan Hu, M.D.
- 電話番号:021-64369181
- メール:zhouwc@tcrximmune.cn
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参加基準
適格基準
就学可能な年齢
- 大人
- 高齢者
健康ボランティアの受け入れ
説明
Screening Period 1
Inclusion Criteria 1:
- Voluntarily participate in the clinical study; fully understand the study and voluntarily sign the informed consent form; be willing to comply with and able to complete all trial procedures.
- Aged 18 to 70 years (inclusive).
- Histologically or cytologically confirmed incurable or metastatic solid tumors that have failed standard treatment, or for which no standard treatment is currently available.
- Expected survival time > 6 months.
- ECOG performance status of 0 or 1.
- Sufficient organ function.
- Patients whose tumor lesions can be collected and from whom tumor-reactive TCR sequences can be identified may enter the study.
- Women of childbearing age must have a negative urine/blood pregnancy test during the screening period and agree to use contraceptive measures for at least 1 year after administration; male subjects whose partners are of childbearing potential must agree to use effective barrier contraception for at least 1 year after administration.
Exclusion Criteria 1:
- A history of other malignant tumors within 2 years prior to signing the informed consent form, except for non-melanoma skin cancer, some in situ carcinomas (e.g., cervical cancer, bladder cancer, breast cancer), or low-risk prostate cancer.
- Uncontrolled infectious diseases within 4 weeks prior to signing the informed consent form.
- Active hepatitis B or hepatitis C virus infection.
- Patients with HIV infection.
- Patients with positive Treponema pallidum.
- A history of any of the following cardiovascular diseases within the past 6 months: New York Heart Association (NYHA) Class III or IV heart failure, coronary angioplasty or stenting, myocardial infarction, unstable angina, or other clinically significant heart diseases.
- Tumor lesions invading the heart or major blood vessels.
- Abnormal pulmonary function indicated by a ratio of forced expiratory volume in 1 second (FEV1) to forced vital capacity (FVC) < 70% in pulmonary function tests.
- A history of clinically significant central nervous system (CNS) disorders, including but not limited to epilepsy, paresis, aphasia, stroke, severe traumatic brain injury, dementia, Parkinson's disease, cerebellar disease, and organic brain syndrome.
- Females who are pregnant or breastfeeding.
- A history of primary immunodeficiency or autoimmune disease.
- Patients whose disease or condition renders them unable to understand, participate in, and/or comply with the study protocol.
- Any other disease that the investigator believes would impair the subject's ability to tolerate protocol treatment or significantly increase the risk of complications.
- Current or past history of psychoactive substance abuse or dependence.
- Subjects whose underlying condition, in the investigator's judgment, may increase the risk of receiving the investigatory drug or confound the interpretation of toxic reactions and adverse events.
- Other conditions deemed unsuitable for participation in the study by the investigator.
Screening Period 2
Inclusion Criteria 2:
The patient's organ function and key test items at this stage should not have significant changes compared with their test results in Screening Period 1. If the patient's test results in Screening Period 2 exceed the following criteria, they should not receive administration of KXV01 Injection until the abnormal items return to the normal range.
- The patient's KXV01 Injection has been successfully prepared.
- Expected survival time > 6 months.
- ECOG performance status of 0 or 1.
- Sufficient organ function.
- Females of childbearing potential have a negative blood pregnancy test within 7 days prior to administration of the study drug (Non-childbearing potential: surgically sterilized or postmenopausal for at least 2 years). In addition, female subjects of childbearing potential must use medically approved contraceptive measures for 12 months after the start of study treatment and have no egg retrieval during this period.
- Male subjects are willing to use medically approved contraceptive measures from the time of signing the informed consent form until 12 months after the start of study treatment, and will not donate sperm during this period.
- At least one measurable lesion according to RECIST v1.1 criteria.
- Toxicities and adverse reactions caused by prior therapy should have resolved to Grade ≤ 1 (except for toxicities considered clinically insignificant, such as chemotherapy-induced alopecia).
Exclusion Criteria 2:
- Prior to administration of the study drug, the subject's anti-tumor therapy has not been sufficiently washed out (2 weeks or 5 half-lives, whichever is shorter).
- Uncontrolled infectious diseases within the previous 4 weeks.
- Active hepatitis B or hepatitis C virus infection.
- Patients with HIV infection.
- Patients with positive Treponema pallidum.
- Tumor lesions invading the heart or major blood vessels.
- A history of clinically significant central nervous system (CNS) disorders, including but not limited to epilepsy, paresis, aphasia, stroke, severe traumatic brain injury, dementia, Parkinson's disease, cerebellar disease, and organic brain syndrome.
- Known primary central nervous system (CNS) malignancy or symptomatic CNS metastases.
- Use of the restricted drugs or treatments between Screening Period 1 and Screening Period 2 per the protocol.
- Females who are pregnant or breastfeeding.
- Subjects whose underlying condition, in the investigator's judgment, may increase the risk of receiving the investigatory drug or confound the interpretation of toxic reactions and adverse events.
- Receipt of major surgery (excluding diagnostic surgery) between Screening Period 1 and Screening Period 2, or expected to undergo major surgery during the study period. Subjects with planned or ongoing minor surgical procedures (such as venous access placement, etc.) are eligible for enrollment.
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)
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:KXV01 TCR Lentinvivo 注射
KXV01 TCRレンチウイルス生体内投与
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KXV01 TCR Lentinvivo注射は、効果的な患者の個別化された腫瘍反応性TCRを持つ第3世代の非複製性自己活性化レンチウイルスベクターの1つです。
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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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用量制限毒性
時間枠:Administraitonの28日後
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DLT評価期間:DLT評価期間は、投与量エスカレーション段階でのKXV01注射の被験者の最初の注入後、28日以内(包括的)以内に定義されます。
すべての有害事象は、CTCAE V5.0に従って等級付けされ、評価する必要があります。
その中で、サイトカイン放出症候群(CRS)および免疫エフェクター細胞関連神経毒性症候群(ICANS)は、米国移植細胞療法(ASTCT)の基準に従って決定および等級付けする必要があります。
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Administraitonの28日後
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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
本研究に関する用語
その他の研究ID番号
- KXV01-R102
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
米国FDA規制機器製品の研究
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