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Clinical Study of JS201 in Patients With Advanced Malignant Tumors

1. april 2022 opdateret af: 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.

Studieoversigt

Status

Rekruttering

Betingelser

Intervention / Behandling

Undersøgelsestype

Interventionel

Tilmelding (Forventet)

244

Fase

  • Fase 1

Kontakter og lokationer

Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.

Studiekontakt

Studiesteder

  • Kina
      • Guangzhou, Kina
        • Rekruttering
        • Sun Yat-sen University Cancer Center
        • Kontakt:
    • Beijing
      • Beijin, Beijing, Kina, 100000
        • Ikke rekrutterer endnu
        • Beiijng Cancer Hospital
        • Kontakt:
    • Fujian
      • Fuzhou, Fujian, Kina, 350000
        • Ikke rekrutterer endnu
        • The First Affiliated Hospital of Fujian Medical University
        • Kontakt:
    • Guangdong
      • Guangzhou, Guangdong, Kina, 510060
        • Ikke rekrutterer endnu
        • Sun Yat-sen University Cancer Center
        • Kontakt:
      • Guangzhou, Guangdong, Kina, 510699
        • Ikke rekrutterer endnu
        • The First Affiliated Hospital of Guangdong Pharmaceutical University
        • Kontakt:
    • Guangong
      • Guangzhou, Guangong, Kina, 510060
        • Ikke rekrutterer endnu
        • Sun Yat-sen University Cancer Center
        • Kontakt:
    • Hebei
      • Baoding, Hebei, Kina, 071030
        • Rekruttering
        • Affiliated Hospital of Hebei University
        • Kontakt:
    • Heilongjiang
      • Harbin, Heilongjiang, Kina, 150000
        • Ikke rekrutterer endnu
        • Harbin Medical University Cancer Hospital
        • Kontakt:
    • Henan
      • Zhengzhou, Henan, Kina, 450003
        • Ikke rekrutterer endnu
        • Henan Cancer Hospital
        • Kontakt:
      • Zhenzhou, Henan, Kina, 450000
        • Ikke rekrutterer endnu
        • The First Affiliated Hospital of Zhengzhou University
        • Kontakt:
    • Hubei
      • Wuhan, Hubei, Kina, 430022
        • Ikke rekrutterer endnu
        • Union Hospital Tongji Medical College Huazhong University of Science and Techonoly
        • Kontakt:
          • Guiling li, Prof
    • Jiangsu
      • Nanjing, Jiangsu, Kina, 210008
        • Ikke rekrutterer endnu
        • Nanjing Drum Tower Hospital
        • Kontakt:
      • Wuxi, Jiangsu, Kina, 214000
        • Ikke rekrutterer endnu
        • Affiliated Hospital of Jiangnan University
        • Kontakt:
      • Xuzhou, Jiangsu, Kina, 221009
        • Ikke rekrutterer endnu
        • Xuzhou Central Hospital
        • Kontakt:
    • Liaoning
      • Shenyang, Liaoning, Kina, 110801
        • Ikke rekrutterer endnu
        • Liaoning cancer Hospital & Institute
        • Kontakt:
    • Shandong
      • Jinan, Shandong, Kina, 250117
        • Ikke rekrutterer endnu
        • Shandong Tumor Hospital
        • Kontakt:
    • Shanghai
      • Shanghai, Shanghai, Kina, 200433
    • Sichuan
      • Chengdu, Sichuan, Kina, 610000
        • Ikke rekrutterer endnu
        • West China Hospital Sichuan University
        • Kontakt:
    • Zhejiang
      • Hangzhou, Zhejiang, Kina, 310005
        • Ikke rekrutterer endnu
        • Cancer Hospital of The University of Chinese Academy of Sciences
        • Kontakt:

Deltagelseskriterier

Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.

Berettigelseskriterier

Aldre berettiget til at studere

18 år til 75 år (Voksen, Ældre voksen)

Tager imod sunde frivillige

Ingen

Køn, der er berettiget til at studere

Alle

Beskrivelse

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.

Studieplan

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

  • Primært formål: Behandling
  • Tildeling: N/A
  • Interventionel model: Enkelt gruppeopgave
  • Maskning: Ingen (Åben etiket)

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Eksperimentel: JS201
Medicin: JS201
JS201 is administered intravenously Q3W at the corresponding dose.

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Number of subjects with DLT (Dose limiting Toxicity)
Tidsramme: 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)
Tidsramme: 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)
Tidsramme: 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)
Tidsramme: Up to 2 years
IrAE is assessed according to the judgement of investigators
Up to 2 years

Sekundære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
anti-drug body (ADA)
Tidsramme: Up to 2 years
incidence of anti-drug body (ADA)
Up to 2 years
peak concentration (Cmax)
Tidsramme: Up to 2 years
Cmax after JS201 administration
Up to 2 years
trough concentration (Ctrough)
Tidsramme: Up to 2 years
Ctrough after JS201 administration
Up to 2 years
area under the plasma drug concentration-time curve (AUC0-t )
Tidsramme: Up to 2 years
AUC0-t after JS201 administration
Up to 2 years
volume of distribution (Vss)
Tidsramme: Up to 2 years
Vss after JS201 administration
Up to 2 years
elimination half-life (t1/2)
Tidsramme: Up to 2 years
t1/2 after JS201 administration
Up to 2 years
clearance rate (CL)
Tidsramme: Up to 2 years
CL after JS201 administration
Up to 2 years
ORR
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Sponsor

Shanghai Junshi Bioscience Co., Ltd.

Datoer for undersøgelser

Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.

Studer store datoer

Studiestart (Faktiske)

29. juli 2021

Primær færdiggørelse (Forventet)

7. juli 2023

Studieafslutning (Forventet)

7. juli 2023

Datoer for studieregistrering

Først indsendt

23. juni 2021

Først indsendt, der opfyldte QC-kriterier

1. juli 2021

Først opslået (Faktiske)

9. juli 2021

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Faktiske)

11. april 2022

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

1. april 2022

Sidst verificeret

1. august 2021

Mere information

Begreber relateret til denne undersøgelse

Yderligere relevante MeSH-vilkår

Andre undersøgelses-id-numre

  • JS201-001-I

Lægemiddel- og udstyrsoplysninger, undersøgelsesdokumenter

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Studerer et amerikansk FDA-reguleret enhedsprodukt

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Kliniske forsøg med Patients With Advanced Malignant Tumors

Kliniske forsøg med JS201

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