Patients With Advanced Malignant Tumors
Conditions
Brief summary
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.
Interventions
DRUGJS201
JS201 is administered intravenously Q3W at the corresponding dose.
Sponsors
Shanghai Junshi Bioscience Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of subjects with DLT (Dose limiting Toxicity) | 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); |
| Number of Subjects with adverse event (AE) | 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. |
| Number of Subjects with serious adverse event (SAE) | 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 |
| Number of Subjects with immune related adverse event (irAE) | Up to 2 years | IrAE is assessed according to the judgement of investigators |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| volume of distribution (Vss) | Up to 2 years | Vss after JS201 administration |
| elimination half-life (t1/2) | Up to 2 years | t1/2 after JS201 administration |
| clearance rate (CL) | Up to 2 years | CL after JS201 administration |
| ORR | 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). |
| anti-drug body (ADA) | Up to 2 years | incidence of anti-drug body (ADA) |
| DCR | 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); |
| PFS | 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. |
| OS | Up to 2 years | OS is defined as the time from the date of randomization to the date of death due to any cause. |
| DOR | 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. |
| peak concentration (Cmax) | Up to 2 years | Cmax after JS201 administration |
| trough concentration (Ctrough) | Up to 2 years | Ctrough after JS201 administration |
| area under the plasma drug concentration-time curve (AUC0-t ) | Up to 2 years | AUC0-t after JS201 administration |
Countries
China
Contacts
Primary ContactPan He, Postgraduate
Outcome results
None listed