A Phase I Study to Evaluate the Safety, Tolerability and Pharmacokinetics of JS004 in Advanced Solid Tumors
A Phase I Clinical Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Recombinant Humanized Monoclonal Antibody Specific to B- and T- Lymphocyte Attenuator, BTLA (JS004) Injection in Patients With Advanced Solid Tumors
1 other identifier
interventional
156
1 country
11
Brief Summary
An open-label, dose-escalation, phase I clinical study to evaluate the safety and tolerability of JS004 injection in the patients with advanced solid tumors who have failure in standard of care and are unable to tolerate standard of care and/or have no available standard of care. The study is divided into screening period, treatment period, and follow-up period.
- 1.Screening period: Subjects will be included in the screening period after signing the informed consent form (ICF). The screening period is up to 28 days, subjects will enter the study treatment period if they meet all the inclusion criteria and none of exclusion criterion.
- 2.Treatment period: Subjects will be allocated to the designated dose group to receive corresponding treatment in accordance with the progress of study. Subjects in dose escalation phase will receive DLT observation at first, and upon completion of DLT observation, the subjects will continue their administration at the original dose if they are tolerated as judged by investigator, until progression of disease, intolerable toxicity or other reasons specified in the protocol. Subjects in the dose extension phase receive appropriate study treatment until disease progression, intolerance of toxicity, or other causes specified in the protocol occur. Response evaluation criteria in solid tumors (RECIST v1.1) will be used for efficacy evaluation every 9 weeks (±7 days) in the first year and every 12 weeks (±7 days) in the 2nd year and thereafter.
- 3.Follow-up period: A safety follow-up visit is required 30 days (±7 days) after the last dose of study drug or before the initiation of new antitumor therapy. If the new antitumor therapy has not been initiated, additional safety follow-up should be completed 90 days (±7 days) after the last dose as far as possible.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Apr 2021
Typical duration for phase_1
11 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 17, 2021
CompletedFirst Posted
Study publicly available on registry
February 26, 2021
CompletedStudy Start
First participant enrolled
April 12, 2021
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 29, 2024
CompletedStudy Completion
Last participant's last visit for all outcomes
August 31, 2024
CompletedAugust 24, 2021
January 1, 2021
2.9 years
January 17, 2021
August 23, 2021
Conditions
Outcome Measures
Primary Outcomes (2)
To evaluate the safety and tolerability of JS004 injection alone and in combination with Toripalimab in patients with advanced solid tumors.
Including incidence of dose limiting toxicity (DLT); incidence and severity of adverse event (AE), serious adverse event (SAE) and immune related adverse event (irAE); laboratory results with clinical significance and other tests with abnormal results.
2 years
Determine the maximum tolerated dose (MTD)/recommended extended dose (RDE) of JS004 injection monotherapy and combination with Toripalimab in patients with advanced solid tumors.
The maximum tolerated dose (MTD) is defined as the maximum dose at which \<1/3 subjects experience any DLTs and at least 6 evaluable subjects are required at each dose level.
2 years
Secondary Outcomes (9)
To preliminarily evaluate the efficacy of JS004 injection as a single drug and combined with Toripalimab.
2 years
To evaluate the pharmacokinetic profile of JS004 Injection as a single drug and combined with Toripalimab.
2 years
To evaluate the pharmacokinetic profile of JS004 Injection as a single drug and combined with Toripalimab.
2 years
To evaluate the pharmacokinetic profile of JS004 Injection as a single drug and combined with Toripalimab.
2 years
To evaluate the pharmacokinetic profile of JS004 Injection as a single drug and combined with Toripalimab.
2 years
- +4 more secondary outcomes
Other Outcomes (3)
To exploratively evaluate the antitumor activity of JS004 injection as a single drug and combined with Toripalimab using iRECIST (2017).
2 years
To explore the pharmacodynamic profile of JS004 injection.
2 years
To explore the correlation of relevant biomarkers with clinical efficacy.
2 years
Study Arms (1)
Dose escalation and extension group
EXPERIMENTAL1. JS004 dose escalation: 1mg/kg, IV Q3W; 3mg/kg, IV Q3W; 10mg/kg, IV Q3W; 2. JS004 dose extension: 3mg/kg, IV Q3W; 200mg, IV Q3W; 3. JS004+Toripalimab Injection dose escalation: JS004 100mg+Toripalimab Injection 240mg, IV Q3W; JS004 200mg+Toripalimab Injection 240mg, IV Q3W; 4. JS004+Toripalimab Injection dose extension: JS004 100mg+Toripalimab Injection 240mg, IV Q3W or JS004 200mg+Toripalimab Injection 240mg, IV Q3W，to be determined.
Interventions
Biological: JS004, Intravenous infusion; Toripalimab Injection, Intravenous infusion
Eligibility Criteria
You may qualify if:
- Only the patients meeting the following criteria are eligible to participate in the study:
- Voluntarily signed written informed consent form;
- Age ≥18 and ≤70 years at the time of signing informed consent form, male or female;
- Life expectancy ≥ 3 months;
- Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1;
- Patients with histologically or cytologically confirmed advanced solid tumors: patients with advanced solid tumors who have failure in standard of care, cannot tolerate standard of care, refuse and/or have no standard of care (melanoma, renal carcinoma and urothelial carcinoma);
- At least one measurable lesion as target lesion (RECIST v1.1);
- Agree to provide tumor tissue specimen ( fresh biopsied sample before treatment should be provided as far as possible, the archived sample within two years is acceptable for the patients who cannot provide fresh biopsied sample before treatment);
- Adequate organ function as indicated by the laboratory results during the screening period;
- Use of effective contraceptive methods during the study for male subjects of reproduction ability or female subjects of childbearing potential, and continuation of contraception for 6 months after the end of treatment;
- Good compliance, cooperation with follow-up.
You may not qualify if:
- Patients will be excluded from the study when they have any of the following conditions:
- History of malignant tumors other than the disease investigated in the past 5 years, however, except for the malignant tumors that can be expected to be cured after treatment;
- Having received systematic antitumor therapy, or local antitumor therapy, or treatment with clinically investigational medication or device within 4 weeks prior to the first dose of study drug;
- Having received immunotherapy within 4 weeks prior to first dose of study drug;
- Previously treated with anti-BTLA or anti-HVEM antibody;
- Adverse reaction induced by previous therapy having not recovered to CTCAE (version 5.0) grade 1 or better;
- Having previously received allogeneic hematopoietic stem cell transplantation or solid organ transplantation;
- Having central nervous system metastases and/or cancerous meningitis;
- Having or suspected to have active autoimmune disease;
- Having hepatitis and liver cirrhosis;
- Massive hydrothorax or ascites with clinical symptoms or requiring symptomatic treatment;
- Having severe cerebro- and cardiovascular diseases;
- Having pulmonary disease;
- Having active infection requiring systemic treatment;
- Positive result for human immunodeficiency virus (HIV) antibody;
- +10 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (11)
Fujian Provincial Cancer Hospital
Fuzhou, Fujian, China
Tumor Hospital affiliated to Harbin Medical University
Harbin, Heilongjiang, China
Hunan Cancer Hospital
Changsha, Hunan, China
Nanjing Drum Tower Hospital
Nanjing, Jiangsu, China
First Hospital of Jilin University
Changchun, Jilin, China
West China Hospital of Sichuan University
Chengdu, Sichuan, China
Run Run Shaw Hospital affiliated to Zhejiang University Medical College
Hangzhou, Zhejiang, China
Zhejiang Cancer Hospital
Hangzhou, Zhejiang, China
Beijing Cancer Hospital
Beijing, China
Fudan University Shanghai Cancer Center
Shanghai, China
Union Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology
Wuhan, China
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Jun Guo
Peking University Cancer Hospital & Institute
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 17, 2021
First Posted
February 26, 2021
Study Start
April 12, 2021
Primary Completion
February 29, 2024
Study Completion
August 31, 2024
Last Updated
August 24, 2021
Record last verified: 2021-01