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Clinical Study of JS201 in Patients With Advanced Malignant Tumors

2022年4月1日 更新者：Shanghai Junshi Bioscience Co., Ltd.

An Open-label, First-in-human, Dose Escalation and Expansion Phase I Clinical Study to Evaluate the Safety, Tolerability and Pharmacokinetic Profile of JS201 in Patients With Advanced Malignant Tumors

This is an open label, phase I clinical study to evaluate the safety, tolerability, pharmacokinetic (PK) profile, pharmacodynamic (PD) profile, immunogenicity and preliminary efficacy of JS201 in the patients with advanced malignant tumors who have progression after or during the standard of care, or no effective standard therapeutic regimen. This study is divided into three phases: dose-escalation phase, dose expansion phase, and clinical expansion phase.

調査の概要

状態

募集

条件

介入・治療

研究の種類

介入

入学 (予想される)

244

段階

  • フェーズ 1

連絡先と場所

このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。

研究連絡先

研究場所

  • 中国
      • Guangzhou、中国
        • 募集
        • Sun Yat-sen University Cancer Center
        • コンタクト：
    • Beijing
      • Beijin、Beijing、中国、100000
        • まだ募集していません
        • Beiijng Cancer Hospital
        • コンタクト：
    • Fujian
      • Fuzhou、Fujian、中国、350000
        • まだ募集していません
        • The First Affiliated Hospital of Fujian Medical University
        • コンタクト：
    • Guangdong
      • Guangzhou、Guangdong、中国、510060
        • まだ募集していません
        • Sun Yat-sen University Cancer Center
        • コンタクト：
      • Guangzhou、Guangdong、中国、510699
        • まだ募集していません
        • The First Affiliated Hospital of Guangdong Pharmaceutical University
        • コンタクト：
    • Guangong
      • Guangzhou、Guangong、中国、510060
        • まだ募集していません
        • Sun Yat-sen University Cancer Center
        • コンタクト：
    • Hebei
      • Baoding、Hebei、中国、071030
        • 募集
        • Affiliated Hospital of Hebei University
        • コンタクト：
    • Heilongjiang
      • Harbin、Heilongjiang、中国、150000
        • まだ募集していません
        • Harbin Medical University Cancer Hospital
        • コンタクト：
    • Henan
      • Zhengzhou、Henan、中国、450003
        • まだ募集していません
        • Henan Cancer Hospital
        • コンタクト：
      • Zhenzhou、Henan、中国、450000
        • まだ募集していません
        • The First Affiliated Hospital of Zhengzhou University
        • コンタクト：
    • Hubei
      • Wuhan、Hubei、中国、430022
        • まだ募集していません
        • Union Hospital Tongji Medical College Huazhong University of Science and Techonoly
        • コンタクト：
          • Guiling li, Prof
    • Jiangsu
      • Nanjing、Jiangsu、中国、210008
        • まだ募集していません
        • Nanjing Drum Tower Hospital
        • コンタクト：
      • Wuxi、Jiangsu、中国、214000
        • まだ募集していません
        • Affiliated Hospital of Jiangnan University
        • コンタクト：
      • Xuzhou、Jiangsu、中国、221009
        • まだ募集していません
        • Xuzhou Central Hospital
        • コンタクト：
    • Liaoning
      • Shenyang、Liaoning、中国、110801
        • まだ募集していません
        • Liaoning Cancer Hospital & Institute
        • コンタクト：
    • Shandong
      • Jinan、Shandong、中国、250117
        • まだ募集していません
        • Shandong Tumor Hospital
        • コンタクト：
    • Shanghai
      • Shanghai、Shanghai、中国、200433
        • まだ募集していません
        • Shanghai Pulmonary Hospital
        • コンタクト：
          • Peng Zhang, Prof
        • コンタクト：
    • Sichuan
      • Chengdu、Sichuan、中国、610000
        • まだ募集していません
        • West China Hospital Sichuan University
        • コンタクト：
    • Zhejiang
      • Hangzhou、Zhejiang、中国、310005
        • まだ募集していません
        • Cancer Hospital of The University of Chinese Academy of Sciences
        • コンタクト：

参加基準

研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。

適格基準

就学可能な年齢

18年～75年 (大人、高齢者)

健康ボランティアの受け入れ

いいえ

受講資格のある性別

全て

説明

Inclusion Criteria

  1. Understanding and voluntarily signing the informed consent form;
  2. Male or female, aged 18 to 70 years (inclusive), for the dose-expansion and clinical expansion parts, aged 18 to 75 years (inclusive);
  3. Patients with histologically or cytologically confirmed advanced malignant tumors who have progression after or on the standard of care, or have no effective standard therapeutic regimen;
  4. In the clinical expansion stage, patients with advanced cervical cancer, lymphoma, non-small cell lung cancer (NSCLC), gastric cancer, urothelial cancer and other malignant solid tumors diagnosed by histology or cytology were enrolled (the details shown in the full protocol);
  5. ECOG PS score: 0~1;
  6. Patients with life expectancy ≥12 weeks;
  7. At least one measurable lesion per RECIST v1.1 (solid tumors) or 2014 Lugano (lymphoma) criteria;
  8. Agree to provide fresh biopsies prior to first dose, or archived samples within two years if there is unpredictable risk of biopsy to the patient（at least 15 fresh biopsy sections or 11 surgical sections). For patients who cannot provide abovementioned sections of tissue samples due to special conditions, it needs to contact with the medical monitor of the sponsor to confirm whether this inclusion criterion can be exempted;

  9. Function of vital organs must meet the followings (no blood transfusion or hematopoietic stimulating factor used within 14 days prior to the first dose

    Absolute neutrophil count (ANC) ≥1.5×109/L;

    Platelet (PL) ≥100×109/L;

    Hemoglobin (Hb) ≥ 9 g/dL;

    Total bilirubin (TBIL) ≤1.5 × ULN; if there is hepatic metastasis, total bilirubin ≤2 × ULN; direct bilirubin (dBIL) ≤ 3.0mg/dL in the patients with Gilbert's syndrome;

    Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 × ULN; or ≤5 × ULN in the patients with hepatic metastasis;

    Serum creatinine (Cr) ≤1.5 × ULN, or calculated creatinine clearance (using Cockcroft -Gault formula) ≥50 mL/min, or 24-hour urine creatinine clearance ≥ 50 mL/min;

    International normalized ratio (INR) ≤1.5 × ULN and activated partial thromboplastin time (aPTT) ≤1.5 × ULN in the patients receiving no anticoagulation therapy;

    QTc interval ≤450 ms for man and ≤470 ms for woman, as calculated using Fridericia's formula;

  10. Female patients of childbearing potential and male patients with partners of childbearing potential must agree to use a medically recognized contraceptive measure (e.g., intrauterine device IUD, contraceptive or condom) during the study and within 3 months after the end of treatment; the serum HCG test must be negative in the female patients with childbearing potential within 7 days prior to enrollment; and the female patients must be not lactating.

Exclusion criteria

  1. Known allergy to any component of JS201;
  2. The patients have previously received the TGF-β/TGF-β receptor targeted drugs;
  3. Received other investigational product within 4 weeks prior to the first dose of JS201;
  4. Accepted major surgery (judged by investigator) or in the recovery period of the surgery within 4 weeks after the first dose of JS201;
  5. Antitumor chemotherapy (6 weeks after the last dose of nitrosourea or mitomycin chemotherapy), radiotherapy, hormone therapy, targeted therapy (for small molecular targeted therapy, within 2 weeks prior to the first dose of JS201), immunotherapy (e.g., anti-PD1/PD-L1 and anti-CTLA-4 therapy) or biotherapy (e.g., cell therapy) within 4 weeks prior to the first dose. Local palliative therapy for isolated lesion is acceptable (e.g., local surgery or radiotherapy), if the tumor evaluation is not affected;
  6. Use of immunosuppressive drug or immune enhancing drugs (such as thymosin, interferon, interleukin, etc.) within 2 weeks prior to the first dose. However, corticosteroid nasal spray, inhaler or ≤10 mg/day systemic prednisone and equivalent similar products are accepted. Short-term use of systemic corticosteroid therapy with a dose equivalent to prednisone > 10 mg / day (e.g. for the treatment/prevention of contrast medium allergy) with ≤ 3 days is allowed;
  7. Previous allogeneic bone marrow transplantation or solid organ transplantation;
  8. Live attenuated vaccine within 30 days prior to the first dose is excluded, and inactivated influenza vaccination is allowed;
  9. Having other malignant tumor other than the disease investigated within 5 years prior to the first dose. The malignant tumors, including but not limited to sufficiently treated thyroid cancer, cervical carcinoma in situ, basal or squamous cell carcinoma of skin, or ductal carcinoma in situ treated with radical surgery, are eligible;
  10. Symptomatic central nervous system (CNS) metastasis requiring intervention (including corticosteroids and antiepileptics). Asymptomatic CNS metastasis previously treated with local therapy is eligible. If the patients confirmed CNS metastasis during screening without any symptoms, and no intervention is required per the standard of care, the eligibility should be determined with the medical monitor of the sponsor;
  11. No remission from the toxicity of previous antitumor therapy, i.e., not resolved to baseline, grade 0-1 per NCI-CTCAE v5.0 (except alopecia) or the level specified in the inclusion/exclusion criteria. Patients with irreversible toxicity reasonably expected to be non-aggravated by the study drug (e.g., hearing loss) can participate in this study upon discussion with the medical monitor of the sponsor;
  12. Patients have accepted anti PD-1/PD-L1 monoclonal antibody treatment, and immune related adverse events occurred that stop the treatment;
  13. Massive pleural effusion, ascites or pericardial effusion with clinical symptoms or requiring symptomatic treatment;
  14. Active autoimmune disease requiring systemic therapy (e.g., corticosteroids or immunosuppressants) within 2 years prior to the first dose.

1) The autoimmune diseases include but not limited to systemic lupus erythematosus, interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, nephritis, hyperthyroidism and multiple sclerosis;

2) Patients with leukoderma or childhood asthma that has been completely relieved and does not need any intervention in adulthood can be enrolled;

3) For the patients combined with rheumatoid arthritis and other joint diseases, Sjogren's syndrome, celiac disease and psoriasis that have been controlled after local therapy, as well as those with positive antinuclear antibody (ANA) and antithyroid antibody, it should be evaluated whether the target organ is involved and systemic treatment is needed, and their enrollment will be determined by investigator;

4) Replacement therapy (e.g., thyroxine, insulin or physiological dose of corticosteroid for adrenal or pituitary insufficiency) will not be regarded as systemic treatment;

5) Patients requiring intermittent use of bronchodilators, inhaled corticosteroids or local injection of corticosteroids for chronic obstructive pulmonary disease (COPD) and asthma can be enrolled.

15. Active infection requiring systematic treatment/antibiotics or intravenous use of systemic anti-infection therapy with 1 week prior to the first dose or use for more than 7 days;

16. History of concurrent serious cerebro- and cardiovascular diseases: ≥grade 3 symptomatic congestive heart failure in accordance with New York Heart Association (NYHA) cardiac function grading system, poorly controlled hypertension or arrhythmia, unstable angina pectoris, myocardial infarction, cerebrovascular accident or transient ischemic attack within 6 months prior to the first doses, or any other arterial thrombosis or embolic event;

17. Presence of active tuberculosis, or interstitial lung disease requiring oral or intravenous steroids or history of pneumonia;

18.Hepatitis (nonalcoholic steatohepatitis and alcoholic/drug-related/autoimmune hepatitis) or cirrhosis;

19. Known positive for human immunodeficiency virus (HIV);

20. Patients with evidence of active infection with hepatitis B virus (HBV) or hepatitis C virus (HCV). Patients with HBcAb positive and/or HBsAg positive in the screening stage, if the patients with HBV DNA copy number < 1000 CPS/ml or < 200 IU/ml can be enrolled. HBsAg positive patients must receive antiviral treatment throughout the study period. Patients with positive HCV antibody in the screening stage can be recruited only when the HCV RNA test result is negative;

21. Any other clinical significant diseases or conditions can effect on the compliance with the protocol (e.g., history of psychosis or drug abuse), the signature of the informed consent form (e.g., drug addiction and drug abuse), or is unsuitable to be involved in this clinical trial, which determined by investigator.

研究計画

このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。

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
実験的：JS201
薬：JS201
JS201 is administered intravenously Q3W at the corresponding dose.

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
Number of subjects with DLT (Dose limiting Toxicity)
時間枠：21 days after first infusion of study drug
DLT is defined as any of the specified toxicities evaluated as at least possibly related with the study drug within 21 days after the first dose (NCI-CTCAE v5.0);
21 days after first infusion of study drug
Number of Subjects with adverse event (AE)
時間枠：Up to 2 years
An Adverse Event (AE) is defined as any new untoward medical occurrences/worsening of pre-existing medical condition without regard to possibility of causal relationship.
Up to 2 years
Number of Subjects with serious adverse event (SAE)
時間枠：Up to 2 years
A Serious Adverse Event (SAE) is an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect
Up to 2 years
Number of Subjects with immune related adverse event (irAE)
時間枠：Up to 2 years
IrAE is assessed according to the judgement of investigators
Up to 2 years

二次結果の測定

結果測定
メジャーの説明
時間枠
anti-drug body (ADA)
時間枠：Up to 2 years
incidence of anti-drug body (ADA)
Up to 2 years
peak concentration (Cmax)
時間枠：Up to 2 years
Cmax after JS201 administration
Up to 2 years
trough concentration (Ctrough)
時間枠：Up to 2 years
Ctrough after JS201 administration
Up to 2 years
area under the plasma drug concentration-time curve (AUC0-t )
時間枠：Up to 2 years
AUC0-t after JS201 administration
Up to 2 years
volume of distribution (Vss)
時間枠：Up to 2 years
Vss after JS201 administration
Up to 2 years
elimination half-life (t1/2)
時間枠：Up to 2 years
t1/2 after JS201 administration
Up to 2 years
clearance rate (CL)
時間枠：Up to 2 years
CL after JS201 administration
Up to 2 years
ORR
時間枠：Up to 2 years
The efficacy evaluated by the investigator in accordance with RECIST 1.1 criteria (solid tumors) or Lugano criteria (2014, lymphoma), including complete response (CR) and partial response (PR).
Up to 2 years
DOR
時間枠：Up to 2 years
DOR is defined as the time from the date of the first documentation of response (confirmed CR or confirmed PR) to the date of the first documentation of PD or death due to any cause, whichever occurs first.
Up to 2 years
DCR
時間枠：Up to 2 years
The efficacy evaluated by the investigator per RECIST 1.1 criteria (solid tumors) or Lugano criteria (2014, lymphoma), including CR, PR and stable disease (SD);
Up to 2 years
PFS
時間枠：Up to 2 years
PFS is defined as the time from the date of randomization to the earlier of the dates of the first documentation of progressive disease or death due to any cause.
Up to 2 years
OS
時間枠：Up to 2 years
OS is defined as the time from the date of randomization to the date of death due to any cause.
Up to 2 years

協力者と研究者

ここでは、この調査に関係する人々や組織を見つけることができます。

スポンサー

Shanghai Junshi Bioscience Co., Ltd.

研究記録日

これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。

主要日程の研究

研究開始 (実際)

2021年7月29日

一次修了 (予想される)

2023年7月7日

研究の完了 (予想される)

2023年7月7日

試験登録日

最初に提出

2021年6月23日

QC基準を満たした最初の提出物

2021年7月1日

最初の投稿 (実際)

2021年7月9日

学習記録の更新

投稿された最後の更新 (実際)

2022年4月11日

QC基準を満たした最後の更新が送信されました

2022年4月1日

最終確認日

2021年8月1日

詳しくは

本研究に関する用語

追加の関連 MeSH 用語

その他の研究ID番号

  • JS201-001-I

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

いいえ

米国FDA規制機器製品の研究

いいえ

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