Advanced Tumors
Conditions
Brief summary
This is an open-label, dose-escalation and dose-expansion phase I clinical study to evaluate the safety and tolerability of JS006 as Monotherapy and in combination with toripalimab in patients with advanced tumors who have failed standard therapies or who have no standard therapy. It is planned to enroll 69-176 patients into the study.
Interventions
DRUGJS006 as Monotherapy
1. JS006 as Monotherapy dose-escalation: JS006, 18/ 60/ 180/ 600/ 1800mg, IV infusion, every 3 weeks (q3w). 2. JS006 as Monotherapy dose-extension: JS006, 1 or 2 specific dose, IV infusion, every 3 weeks (q3w).
DRUGJS006 in combination with Toripalimab
1. JS006 in combination with Toripalimab dose-escalation: JS006, 2 or 3 specific dose, IV infusion, every 3 weeks (q3w), combined with Toripalimab, 240mg, IV infusion, every 3 weeks (q3w). 2. JS006 in combination with Toripalimab dose-extension: JS006, 1 or 2 specific dose, IV infusion, every 3 weeks (q3w), combined with Toripalimab, 240mg, IV infusion, every 3 weeks (q3w). 3. JS006 in combination with Toripalimab indications expansion: JS006, RP2D, IV infusion, every 3 weeks(q3w), combined with Toripalimab, 240mg, IV infusion, every 3 weeks (q3w).
Sponsors
Shanghai Junshi Bioscience Co., Ltd.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Understanding and signature of the informed consent form voluntarily; 2. Age 18 - 75 years (inclusive), male or female; 3. Pathologically confirmed advanced malignancy who have failed standard treatment or with no standard treatment available; 4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1; 5. Expected survival ≥ 12 weeks; 6. Having at least one measurable lesion that meets RECIST v1.1 criteria or Lugano 2014 criteria; 7. The function of vital organs meets the following requirements (no blood transfusion or blood products and no hematopoietic stimulating factors and other drugs to correct blood cell counts within 14 days before the examination): 7-1.Absolute neutrophil count (ANC) ≥1.5 × 109/L; 7-2. Platelet count (PLT) ≥ 90 × 109/L; 7-3.Hemoglobin (Hb) ≥ 90 g/L; 7-4.Total bilirubin (TBIL) ≤ 1.5 × ULN, or for patients with liver metastases or Gilbert syndrome, TBIL ≤ 3 × ULN; 7-5.Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 × ULN, or for patients with liver metastases, ALT and AST ≤ 5 × ULN; 7-6.Serum creatinine (Cr) ≤ 1.5 × ULN, or calculated creatinine clearance (Cockcroft-Gault formula) ≥ 50 mL/min; 7-7.For patients not receiving anticoagulant therapy, international normalized ratio (INR), prothrombin time (PT) and activated partial thromboplastin time (aPTT) ≤1.5 × ULN; For patients receiving anticoagulation therapy (such as low molecular weight heparin or warfarin) require a stable dose of anticoagulant drugs for at least 4 weeks without dose adjustment; 7-8.QTc interval calculated according to Fridericia's criteria ≤ 450 ms for males and ≤ 470 ms for females; 8. Female patients of childbearing potential and male patients whose partners are women of childbearing potential are willing to use effective contraceptive measures during the study treatment and for 6 months after the last dose; Female patients of childbearing potential must have a negative serum HCG test within 7 days before study enrollment and must be non-lactating. The childbearing potential is defined as a woman who has not undergone surgical sterilization, hysterectomy and/or bilateral oophorectomy or who is not postmenopausal (amenorrhea ≤ 12 months).
Exclusion criteria
Patients who met any of the following criteria will be excluded from the study: 1. Known allergic to toripalimab or ingredients of JS006; 2. Have received anti-TIGIT or related targets CD155, CD112 or CD113 antibody treatment in the past; 3. Participation in other clinical studies within 4 weeks before the first dose, except for an observational (non-interventional) clinical study or follow-up period of an interventional study; 4. Major surgery (as judged by the investigator) within 4 weeks before the first dose or in the recovery period of surgery; 5. Received systemic anti-tumor therapy within 4 weeks before the first dose, such as chemotherapy (or within 6 weeks for the last chemotherapy with nitrosourea or mitomycin), radiotherapy, targeted therapy, immunotherapy or biological therapy. Received traditional Chinese medicine or Chinese patent medicine with anti-tumor indications within 2 weeks before the first dose of JS006. Hormone therapy, such as insulin for diabetes, hormone replacement therapy, etc., is acceptable for non-tumor-related diseases. Local palliative treatment (such as local surgery or radiotherapy) for isolated lesions can be accepted without affecting the efficacy evaluation; 6. Patients who discontinued prior immunotherapy due to immune-related adverse reactions; 7. Received immunosuppressive medications within 4 weeks before the first dose, except corticosteroid nasal spray, inhalers, or systemic prednisone ≤ 10 mg/day or equivalent; 8. Received allogeneic bone marrow transplantation or solid organ transplantation in the past; 9. Patients who received live attenuated vaccination within 30 days before the first dose; 10. Patients with two or more malignancies within 5 years before the first dose, except for early malignancy (carcinoma in situ or stage I tumors) that have been cured, such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer; 11. Presence of central nervous system (CNS) metastases that are symptomatic, untreated, or require continued treatment (including corticosteroids and antiepileptic drugs). Patients who previously received treatment but were clinically stable for at least 4 weeks before enrollment can be enrolled, excluding patients with evidence of new or expanded metastasis and discontinued steroid therapy; 12. The toxicity has not resolved after prior anti-tumor therapy, which means do not recover to baseline, NCI-CTCAE 5.0 Grade 0 to 1 (except alopecia, pigmentation) or the level specified in the inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To evaluate the safety and tolerability of JS006 as Monotherapy and in combination with toripalimab in patients with advanced tumors | 2 years | Incidence and severity of dose limiting toxicity (DLT), adverse events (AEs), serious adverse events (SAEs), and immune-related adverse events (irAEs); abnormal changes with clinical significance in the laboratory and other tests |
| Determing the maximum tolerated dose and the recommended phase II dose for JS006 as Monotherapy and in combination with toripalimab in patients with advanced tumors | 2 years | Maximum tolerated dose: Dose Limitted Toxictiy events occurred at a rate less than 1/3 of the maximum tolerated dose. Phase II recommended dose: safety, pharmacokinetics, and preliminary efficacy data of dose escalation will be integrated. When the Maximum tolerated dose(MTD) is determined, the Maximum tolerated dose(MTD) is usually used as the Phase II recommended dose(RP2D), or the dose lower than the Maximum tolerated dose(MTD) is selected as the Phase II recommended dose(RP2D) based on the comprehensive data. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetic (PK) profile: JS006 | 2 years | JS006 concentrations in individual subjects at different time points after dosing of JS006. |
| To determine the immunogenicity of JS006 as monotherapy and in combination with toripalimab in patients with advanced tumors | 2 years | Immunogenicity: incidence of anti-drug antibodies (ADAs) and/or neutralizing antibodies (Nabs) of JS006 and toripalimab. |
| Within 1 hour before the first administration to 90 ±7 days after the last administration. | 2 years | Peripheral blood immune cell subset and receptor occupancy of TIGIT |
| Objective response rate (ORR) | 2 years | The percentage of cases with remission (PR + CR) after treatment was assessable. |
| Duration of response (DOR) | 2 years | The time from the first assessment of CR or PR to the first assessment of PD or death due to any cause. |
| Disease control rate (DCR) | 2 years | The percentage of cases with remission (PR + CR) and stable lesions (SD) after treatment was assessable. |
| Time to response (TTR) | 2 years | time from the start of treatment to progression of diease. |
| Progression-free survival (PFS) | 2 years | PFS is defined as time from the start of treatment to progression of disease or death. |
| Overall survival (OS) | 2 years | Overall survival is defined as time from the start of treatment until death due to any reason. |
Countries
China
Outcome results
None listed