Advanced Solid Tumor
Conditions
Brief summary
A 3-part (dose-escalation, dose-expansion and cohort-expansion) phase I clinical study of JS004 in subjects with advanced solid malignancies in China for the first time, to evaluate the safety, tolerability, PK, immunogenicity, antitumor activity and biomarkers of JS004, define the MTD and RP2D. A cycle is 21 days (3 weeks) which includes JS004 being administered IV Q3W. All patients will be treated until disease progression per RECIST v1.1 and iRECIST, or intolerable toxicity per CTCAE 5.0, withdrawal of consent, or end of the study, whichever occurs first.Disease progression must be confirmed at least 4 weeks but no longer than 8 weeks after initial documentation of progression.
Interventions
BIOLOGICALDrug: JS004, Recombinant humanized IgG4κ monoclonal antibody specific to BTLA for injection Intravenous infusion
Drug: JS004, Recombinant humanized IgG4κ monoclonal antibody specific to BTLA for injection Intravenous infusion
Sponsors
Shanghai Junshi Bioscience Co., Ltd.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Able to understand and willing to sign the Informed Consent Form; 2. 18-70 years(included), male or female; 3. Subjects with histologically or cytologically confirmed advanced solid tumor. 4. In Dose Escalation and Dose Expansion, patients must have received, or be ineligible for or intolerant of all available approved or standard therapies known to confer clinical benefit, or for whom no standard therapy exists; in Indication Extension, patients with advanced solid tumors, who must have received at least one line of therapy for advanced or metastatic disease, but are not required to have received all standard therapies known to confer clinical benefit; 5. ECOG performance status of 0 or 1; 6. Life expectancy ≥12 weeks; 7. At least one measurable lesion per RECISTv1.1 and iRECIST; 8. Willingness to provide consent for fresh pre-treatment biopsies, or,an archival specimen could be required within two years prior to the first dose of study drug; 9. Adequate organ and marrow function per protocol specifically defined; 10. Females of childbearing potential ,and males who are sexually active with a female partner of childbearing potential, must use effective contraception from time of screening, and must agree to continue using such precautions for 3 months after the final dose of JS004; HCG testing will be conducted and negative result within 7 days before randomization for females of childbearing potential, and must not be breast-feeding;
Exclusion criteria
1. Known allergic reaction to any monoclonal antibody or the ingredients and compositions of JS004 . 2. Prior exposure to anti-BTLA, or anti-HVEM antibodies. 3. Concurrent enrollment in another clinical study within 4 weeks prior to first dose of JS004, unless it is an observational (non-interventional) clinical study or the follow-up period of an interventional study. 4. Major surgery (as defined by the investigator) within 4 weeks prior to first dose of JS004 or still recovering from prior surgery.Any concurrent chemotherapy within 4 weeks prior to first dose of JS004 , radiotherapy, immunotherapy, or biologic therapy for cancer treatment. Traditional Chinese/Chinese Patent Medicine preparations within 2 weeks prior to first dose of JS004 for treating tumors approved by NMPA.Concurrent use of hormones for non-cancer-related conditions (e.g., insulin for diabetes and hormone replacement therapy) is acceptable. Isolated lesions for palliative intent is acceptable (e.g., by local surgery or radiotherapy) without influence in efficacy assessment. 5. Patients who have discontinued prior immune therapy due to immune mediated adverse reaction(s). 6. Current or prior use of immunosuppressive medication within 4 weeks prior to the first dose of JS004, with the exception of intranasal and inhaled corticosteroids or systemic corticosteroids not to exceed 10 mg/day of prednisone or equivalent. 7. Prior allogeneic bone marrow transplantation or prior solid organ transplantation. 8. Receipt of live attenuated vaccination within 30 days of receiving JS004. 9. Two or more malignant tumors within 5 years prior to the first dose of JS004. Except the following conditions: radically cured early malignant tumor (carcinoma in situ or stage I tumor), for example, adequately treated cervical carcinoma in situ, basal or squamous cell skin cancer. 10. Symptomatic or untreated central nervous system (CNS) metastases or requiring ongoing treatment for CNS metastases, including corticosteroids and antiepileptic agents. Subjects with previously treated brain metastases may participate unless clinically stable for at least 4 weeks prior to study entry, have no evidence of new or enlarging metastases, and are off steroids. 11. Unresolved toxicities from prior anticancer therapy, defined as having not resolved to baseline or to NCI-CTCAE v5.0 Grade 0 or 1, or to levels dictated in the inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| DLT, MTD, Number of participants and severiaty with treatment-related Adverse events (AEs) as assessed by CTCAE v5.0 | 2 years | DLT, MTD, Number of participants and severity with treatment-related Adverse events (AEs) as assessed by CTCAE v5.0 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| DOR | 2 years | Duration of Response (DOR) by RECIST 1.1 |
| DCR | 2 years | Disease Control Rate (DCR) by RECIST 1.1 |
| PFS | 2 years | Progression-free survival(PFS) by RECIST 1.1 |
| OS | 2 years | Overall survival(OS) by RECIST 1.1 |
| RO | 2 years | BTLA receptor of occupancy (RO) of blood |
| Cmax | 2 years | Maximum Plasma Concentration(Cmax) after injection of JS004 |
| Tmax | 2 years | Perk Time(Tmax) after injection of JS004 |
| Area Under the Cure(AUC) after injection of JS004 | 2 years | AUC |
| t1/2 half life | 2 years | t1/2 after injection of JS004 |
| Plasma Clearance(CL) | 2 years | Plasma Clearance(CL) after injection of JS004 |
| Volume of distribution(V) | 2 years | Apparent volume of distribution after injection of JS004 |
| Cmin | 2 years | Minimum Plasma concentration(Cmin) of steady state after multiple dose injection of JS004 |
| volume of distribution of steady state (Vss) | 2 years | Apparent volume of distribution of steady state (Vss) after multiple dose injection of JS004 |
| ADA | 2 years | The presence of anti-drug antibody (ADA) after multiple dose injection of JS004 |
| ORR | 2 years | Objective Response Rate(ORR) by RECIST 1.1 |
Other
| Measure | Time frame | Description |
|---|---|---|
| Predictive biomarkers | 2 years | Predictive biomarkers, including but not limited to, BTLA and HVEM |
Countries
China
Outcome results
None listed