A Study Explore JS001+JS002 in Patients With Advanced Cancer

• Status: Not yet recruiting
• Trial end date: 2024-04-27
• Target enrollment: 0
• Participant gender: All

Summary

This open-label phase I clinical study with clinical development phase will evaluate the safety, tolerability, pharmacokinetics and preliminary efficacy of JS002 combined with Toripalimab in advanced cancer patients, who has failed standard therapy OR could not tolerate standard therapy OR refused/had no standard therapy.

This study is divided into two parts:

Part A. JS002 combined with Toripalimab dose escalation and dose expansion phase; Part B.JS002 combined with Toripalimab clinical expansion phase.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Shanghai Junshi Bioscience Co., Ltd.

Criteria

Inclusion criteria:

1. Fully understand and be willing to provide written informed consent;

2. Male or female with age ≥ 18 years and ≤75 years(At part B age≥18 years);

3. The expected survival is ≥ 3 months;

4. ECOG PS 0 or 1;

5. Advanced tumor patients who have failed standard treatment (including PD-1/PD-L1), cannot tolerate standard treatment, refuse/have no standard treatment (note: Patients with hepatocellular carcinoma, lung cancer and urothelial carcinoma that have failed PD-1 or PD-L1 treatment are mainly treated, and can be appropriately extended to other patients without standard treatment according to initial efficacy);

6. Having at least one measurable disease per RECIST 1.1.

7. Agree to provide tumor tissue samples (fresh biopsy samples before treatment should be provided as far as possible; for patients who cannot provide fresh biopsy samples before treatment, archived samples can be provided within 2 years; for some subjects who cannot provide qualified tumor tissue samples, they can also be included in the group after discussion and agreement between the investigator and the sponsor);

8. The results of laboratory tests during the screening period indicate that the subject has good organ function:

a) Hematology (no blood transfusion within 14 days and no treatment with blood components or granulocyte colony cytokines) : i. Absolute neutrophil count ANC ≥ 1.5×109/L(1,500/mm3) ii. Platelets ≥ 100×109/L(Part B: ≥ 75×109/L) (100,000/mm3) iii. Hemoglobin ≥ 10.0g/dL (Part B: ≥ 9.0g/dL)

b)Hepatic function: i. Serum total bilirubin(TBil) ≤1.5×ULN ; For subjects with primary liver cancer, liver metastasis, or proven/suspected Gilbert's disease, TBil ≤ 2×ULN ii. AST and ALT ≤2.5 × ULN; ≤5×ULN in those with hepatic metastasis or primary liver cancer.

c)Renal function: i. Creatinine clearance(CrCl) ≥50mL/min(Cockcroft-Gault formula) ii. Urine protein ≤2+ (if the urine protein is 2+, urine protein should be collected for measurement within 24 hours, and the total amount should be ≤2g before inclusion)

d)Coagulation function: i. International standardized ratio (PT/INR) and activated partial thrombin time (APTT) ≤1.5×ULN (for those receiving anticoagulant therapy, such as low molecular weight heparin or warfarin, the anticoagulant dose is required to be stable for at least 4 weeks without dose adjustment, and the coagulation parameters INR and APTT at screening are within the expected range of anticoagulant therapy)

e)Endocrine function: Thyroid stimulating hormone (TSH) normal, or abnormal TSH but normal FT3 and/or FT4 (for patients with hypothyroidism with abnormal TSH but normal FT4)

f)Cardiac function: QTc interval calculated according to Fridericia formula was 460 ms for male and 480 ms for female

9. Fertile men or women at risk of becoming pregnant used an effective method of contraception (e.g., oral contraceptives, intrauterine devices, or barrier contraception combined with spermicide) and continued to use contraception for 6 months after treatment.

10. Good compliance and follow-up.

Exclusion criteria:

1. A history of malignancies other than the disease under study within the past 5 years, with the exception of early malignancies that have been completely cured (no recurrence within 5 years) (including but not limited to adequately treated thyroid cancer, carcinoma in situ of the cervix, basal or squamous cell skin cancer, or ductal carcinoma in situ of the breast treated by radical surgery);

2. The first study medication received systemic antitumor drugs within 4 weeks before treatment, including chemotherapy, small molecular targeted drug therapy, hormone therapy, immunotherapy or biological treatment, etc.), or local anti-tumor therapy (such as radiation therapy, tumor > 2 weeks before baseline detection for bone metastases palliative radiotherapy is acceptable), or clinical research drug or treatment instrument;

3. Patients who have previously received anti-PCKS9 antibody therapy;

4. Adverse reactions caused by previous treatment have not recovered to GRADE 1 or below CTCAE (version 5.0) (except alopecia and neurotoxicity, which researchers judged could not be recovered for a long time);

5. Previous allogeneic hematopoietic stem cell transplantation or solid organ transplantation;

6. Have untreated central nervous system metastasis, or meningeal metastasis. Has received treatment of brain metastases subjects, if at least 3 months in a stable condition, in the first study to give medicine has not occurred within 4 weeks before imaging, disease progression, and all the nervous system symptoms has returned to baseline levels, no new evidence or expand brain metastases, and at least 28 days before the delivery for the first time in research and treatment has stopped radiation, surgery or steroid therapy, can enter the group;

7. Autoimmune diseases, including but not limited to systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, etc. in the past 2 years. Exceptions: Type I diabetes that can be controlled by alternative therapy alone, skin diseases that do not require systemic treatment (e.g., psoriasis, vitiligo); Patients with endocrine diseases that have been controlled by hormone replacement therapy, such as hypothyroidism, can be included;

8. Patients with associated clinical symptoms (dyspnea, wheezing, abdominal distension, etc.), uncontrolled or repetitive drainage of pleural/abdominal effusion or pericardial effusion.

9. Have serious cardiovascular and cerebrovascular diseases, such as poorly controlled hypertension (systolic blood pressure > 150mmHg and/or diastolic blood pressure > 100mmHg) or pulmonary hypertension as judged by the investigator; Unstable angina or myocardial infarction, coronary artery bypass grafting or stenting within 6 months prior to study use; Chronic heart failure with heart function grade 2 or greater (NYHA); Degree ⅱ or higher heart block; Left ventricular ejection fraction (LVEF) < 50%; Grade ≥2 supraventricular or ventricular arrhythmias; Cerebrovascular accident (CVA) or transient ischemic attack (TIA) occurred within 6 months prior to medication;

10. History of pulmonary disease: drug-induced interstitial lung disease or pneumonia, obstructive pulmonary disease that severely affects lung function, and symptomatic bronchospasm;

11. Has an active infection requiring systemic treatment;

12. Human immunodeficiency virus (HIV) antibody test positive;

13. Persons with non-alcoholic steatohepatitis, alcoholic or drug-related, or autoimmune hepatitis) or uncontrolled active hepatitis B virus (HBV), hepatitis C virus (HCV), or hepatitis D virus (HDV) :

A) Active viral hepatitis is defined as: HBV infection refers to HBV surface antigen (HBsAg) positive and HBV DNA detected by each research center is higher than the upper limit of the reference value of the center, and can be accompanied by a continuous increase in ALT; Or HCV infection, defined as positive antibodies to HCV and POSITIVE HCV RNA; Or HDV infection, defined as positive for HDV antigen.

B) Patients with active HBV should take antiviral drugs, such as nucleoside (acid) analogues (NAs), as recommended in the Guidelines for the Prevention and Treatment of Chronic Hepatitis B (2019 edition). Before randomization, patients with HBV DNA < 2000 IU/ mL could participate in this study.

C) Patients who test positive for HCV antibodies can only be enrolled in this study if the polymerase chain reaction (PCR) test is negative for HCV RNA. D) If the patients were receiving antiviral therapy at the time of enrollment and were required to maintain stable antiviral therapy throughout the study, any patients with compliance concerns were excluded from enrollment.

14. Active tuberculosis (TB) is known to exist. Subjects suspected of having active TB should be examined for chest X-rays, sputum, and clinical signs and symptoms.

15. Received systemic corticosteroids (prednisone > 10mg/ day or equivalent) or other immunosuppressive drugs within 14 days prior to the first study;

16. In the first study, broad-spectrum antibiotics that may affect intestinal flora were used within 14 days before administration;

17. Receiving live or attenuated live vaccine within 4 weeks prior to initial study administration;

18. Major surgical procedures (as defined by the investigator, e.g., open biopsy, severe trauma, etc.) were performed within 4 weeks prior to medication in the first study. Note: Intravenous drip replacement is acceptable. Had a major surgical procedure planned within 30 days of initial dosing (as determined by the investigator) or had not fully recovered from prior surgery. Local surgery (e.g., placement of systemic ports, hollow-core needle biopsies, and prostate biopsies) is permitted, provided that the procedure is performed at least 24 hours before the first administration of the investigational therapeutic agent;

19. Those who have a history of psychotropic drug abuse and cannot get rid of it or have a history of mental disorders;

20. Pregnant or lactating women;

21. Known allergy to JS002 or Toripalimab and its components;

22. Other severe, acute or chronic medical or psychiatric conditions or laboratory abnormalities that, in the investigator's judgment, may increase the risk associated with study participation or may interfere with the interpretation of study results.