The Study to Evaluate Toripalimab (JS001) in Patients With Advanced GC, ESCC, NPC, HNSCC
- Conditions
- Head and Neck Squamous Cell CarcinomaGastric AdenocarcinomaEsophageal Squamous Cell CarcinomaNasopharyngeal Carcinoma
- Interventions
- Biological: 3 mg/kg anti-PD-1 mAb JS001 Q2WBiological: 360 mg anti-PD-1 mAb JS001 Q3WBiological: 240mg anti-PD-1 mAb JS001 Q3W
- Registration Number
- NCT02915432
- Lead Sponsor
- Shanghai Junshi Bioscience Co., Ltd.
- Brief Summary
The purpose of this study is to preliminarily evaluate anti-tumor activity of a Recombinant Humanized Anti-PD-1 Monoclonal Antibody for Infusion (JS001) in treating advanced gastric adenocarcinoma, esophageal squamous cell carcinoma, nasopharyngeal carcinoma and head and neck squamous cell carcinoma and to determine the recommended phase II dose (RP2D)
- Detailed Description
Overall Design:
This is a multicenter, open-label, phase Ib/II clinical study of Toripalimab Injection (JS001) in patients with gastric adenocarcinoma (GC), esophageal squamous cell carcinoma (ESCC), nasopharyngeal carcinoma (NPC), or head and neck squamous cell carcinoma (HNSCC). On the basis of the results of safety and pharmacokinetic data in the phase I study of JS001, 3 mg/kg is determined as the recommended dose of the 2-week monotherapy regimen, and no study on the 10 mg/kg cohorts will be conducted any more. And the corresponding 240 mg and 360 mg are determined as the corresponding exploratory doses of the 3-week combined treatment regimens.
Eligible subjects will be selected based on the inclusion and exclusion criteria: subjects with gastric adenocarcinoma, esophageal squamous cell carcinoma, nasopharyngeal carcinoma, or head and neck squamous cell carcinoma (cohort 1, 2, 3, 4, respectively) will receive treatment at the dose of 3 mg/kg. While subjects with advanced gastric adenocarcinoma, esophageal squamous cell carcinoma, nasopharyngeal carcinoma, or head and neck squamous cell carcinoma (cohort 5, 6, 7, 8, respectively), who have not received any treatment before, will be treated with the corresponding 3-week regimen of standard first-line chemotherapy combined with JS001 240 mg or 360 mg .
Study Treatment:
The study on the 3 mg/kg cohorts is planned to be conducted first in cohort 1, 2, 3, 4 in this trial. After enrollment, the subjects will receive study treatment once every 2 weeks (Q2W) with 4 weeks as a cycle, until absence of further benefits judged by the investigator, disease progression, occurrence of intolerable toxicity, investigator's decision, withdrawal of informed consent by the subject, or death.
The study of cohort 5, 6, 7, and 8 will be carried out in the sites designated by the sponsor. Subjects will receive corresponding regimen of standard first-line chemotherapy combined with JS001 240 mg or 360 mg once every 3 weeks (Q3W) (see Section 3.1 Overall Design for details). JS001 240 mg or 360 mg Q3W can be administrated after the end of chemotherapy until absence of further benefits judged by the investigator, disease progression, occurrence of intolerable toxicity, investigator's decision, and withdrawal of informed consent by the subject, or death.
If the subject experiences disease progression but the subject can still obtain clinical benefit from the study treatment of JS001 according to the investigator, the subject can continue the study treatment if an approval is obtained after discussion between the investigator and the medical monitor from the sponsor or the authorized CRO. If the subject develops disease progression for a second time, he/she should permanently withdraw from the study treatment.
Tumor Assessment:
During the study, for cohort 1, 2, 3, and 4, tumor responses will be evaluated every 8 weeks in the first year according to RECIST 1.1, and every 12 weeks thereafter. Tumor responses will also be evaluated according to irRECIST at the same frequency with that conducted according to RECIST 1.1 until disease progression, death or loss of follow up (whichever comes first). For cohort 5, 6, 7, and 8, tumor responses will be evaluated every 6 weeks (± 3 days) in the first year according to RECIST 1.1 and irRECIST, and every 12 weeks thereafter until disease progression, death or loss of follow up (whichever comes first).
The radiographic data of the subjects will be collected for review by IRC. The IRC will evaluate the corresponding study endpoints based on tumor responses, but no such evaluation is planned for cohort 5, 6, 7 and 8.
Pharmacokinetics:
At least 10 of the subjects (no requirements on indications) in JS001 3 mg/kg cohorts at the sponsor-designated study sites should complete the pharmacokinetic blood sampling in the first 3 cycles of study treatment until 60 days after the end of study treatment. If a subject did not complete the scheduled sample collection in the first 3 cycles of study treatment due to any reason, another subject should be added.
Corresponding pharmacokinetic blood samplings will also be conducted for cohort 5, 6, 7, and 8, to evaluate the pharmacokinetic characteristics of JS001 used in the combined treatment with chemotherapy. At least 3 patients will be selected for blood sampling in each cohort.
Acquisition of Tumor Tissue Specimens:
Subjects with esophageal squamous cell carcinoma, gastric adenocarcinoma (including adenocarcinoma at esophageal-gastric conjunction), nasopharyngeal carcinoma, or head and neck squamous cell carcinoma must provide acceptable tumor tissue specimens (fresh tumor tissue specimens for biopsy before enrollment are preferred) prior to enrollment for future use in subsequent exploratory studies.
Any subject with the response confirmed as partial response (PR) and/or progressive disease (PD) is encouraged to voluntarily participate in the selectable biomarkers study if tumor tissues can be obtained from him/her. And in the selectable biomarkers study, they will provide tumor tissues for exploratory study on the correlation between tumor markers and the level of anti-tumor responses.
All the tumor tissue specimens provided will be sent to the designated central laboratory for evaluation.
End of Study:
The primary endpoint of the study is ORR. The study will be completed at 12 months after the last patient in and data analysis will be conducted then. If by that time there are still some subjects receiving study treatment, these subjects will be transferred to an extension study to continue the study treatment until absence of further benefits judged by investigator, disease progression, occurrence of intolerable toxicity, investigator's decision, withdrawal of informed consent by subject, or death.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 401
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- FACTORIAL
- Arm && Interventions
Group Intervention Description 3 mg/kg anti-PD-1 mAb JS001 Q2W 3 mg/kg anti-PD-1 mAb JS001 Q2W Subjects will be eligible for this study after they fulfill the inclusion criteria and exclusion criteria. Subjects diagnosed as the gastric adenocarcinoma, esophageal squamous cell carcinoma, nasopharyngeal carcinoma, or head and neck squamous cell carcinoma will receive treatment at the dose of 3 mg/kg. 360 mg anti-PD-1 mAb JS001 Q3W 360 mg anti-PD-1 mAb JS001 Q3W Subjects will receive corresponding regimen of standard first-line chemotherapy combined with JS001 360 mg once every 3 weeks (Q3W). JS001 360 mg Q3W can be administrated after the end of chemotherapy until absence of further benefits judged by the investigator, disease progression, occurrence of intolerable toxicity, investigator's decision, and withdrawal of informed consent by the subject, or death. 240mg anti-PD-1 mAb JS001 Q3W 240mg anti-PD-1 mAb JS001 Q3W Subjects will receive corresponding regimen of standard first-line chemotherapy combined with JS001 240 mg once every 3 weeks (Q3W). JS001 240 mg Q3W can be administrated after the end of chemotherapy until absence of further benefits judged by the investigator, disease progression, occurrence of intolerable toxicity, investigator's decision, and withdrawal of informed consent by the subject, or death
- Primary Outcome Measures
Name Time Method Objective response rate (ORR) evaluated based on Response Evaluation Criteria in Solid Tumors (RECIST 1.1) Up to 1.5 approximately years To preliminarily evaluate the anti-tumor activity of Toripalimab Injection (former name: Recombinant humanized anti-PD-1 monoclonal antibody for injection, JS001) in treating advanced gastric adenocarcinoma, esophageal squamous cell carcinoma, nasopharyngeal carcinoma, and head and neck squamous cell carcinoma.
- Secondary Outcome Measures
Name Time Method Duration of response (DOR) Up to 1.5 approximately years Disease control rate (DCR) Up to 1.5 approximately years Progression free survival (PFS) Up to 1.5 approximately years Overall survival (OS) Up to 1.5 approximately years afety: incidence and severity of adverse events, and clinically significant laboratory abnormalities Up to 1.5 approximately years The frequencies of positive and negative anti-drug antibody (ADA) test compared with baseline Up to 1.5 approximately years Maximum Plasma Concentration (Cmax) after single dose injection of Anti-PD-1 Monoclonal Antibody (mAb) Up to 1.5 approximately years Peak Time (Tmax) after single dose injection of Anti-PD-1 mAb Up to 1.5 approximately years Area Under the Curve (AUC) after single dose injection of Anti-PD-1 mAb Up to 1.5 approximately years t1/2 after single dose injection of Recombinant Humanized Anti-PD-1 mAb Up to 1.5 approximately years Plasma clearance (CL) after single dose injection of Anti-PD-1 mAb Up to 1.5 approximately years Apparent volume of distribution (V) after single dose injection of Anti-PD-1 mAb Up to 1.5 approximately years Minimum Plasma Concentration (Cmin) of steady state after multiple dose injection of Anti-PD-1 mAb Up to 1.5 approximately years Apparent volume of distribution of steady state (Vss) after multiple dose injection of Anti-PD-1 mAb Up to 1.5 approximately years
Trial Locations
- Locations (23)
Hunan Cancer Hospital
🇨🇳Changsha, Hunan, China
Fudan University Shanghai Cancer Center
🇨🇳Shanghai, Shanghai, China
Sun Yat-sen University Cancer center
🇨🇳Guangzhou, Guangdong, China
Fujian Medical University Union Hospital
🇨🇳Fuzhou, Fujian, China
Tumor Hospital of Hebei Province
🇨🇳Shijiazhuang, Hebei, China
Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology
🇨🇳Wuhan, Hubei, China
The First People's Hospital of Changzhou
🇨🇳Changzhou, Jiangsu, China
The First Hospital of China Medical University
🇨🇳Shenyang, Liaoning, China
Beijing Cancer Hospital
🇨🇳Beijing, Beijing, China
Liuzhou Worker's Hospital
🇨🇳Liuzhou, Guangxi, China
West China Hospital，Sichuan University
🇨🇳Chengdu, Sichuan, China
Tianjin Medical University Cancer Institute & Hospital
🇨🇳Tianjin, Tianjin, China
Harbin Medical University Cancer Hospital
🇨🇳Harbin, Heilongjiang, China
The General Hospital of the People's Liberation Army (PLAGH)
🇨🇳Beijing, Beijing, China
Henan Cancer Hospital
🇨🇳Zhengzhou, Henan, China
Cancer Hospital of Shantou University Medical College
🇨🇳Shantou, Guangdong, China
Southern Medical University Nanfang Hospital
🇨🇳Guangzhou, Guangdong, China
Jiangsu Province Hospital
🇨🇳Nanjing, Jiangsu, China
Jiangsu Cancer Hospital
🇨🇳Nanjing, Jiangsu, China
The First Affiliated Hospital of Medical School of Zhejiang University
🇨🇳Hangzhou, Zhejiang, China
The First Hospital of Jilin University
🇨🇳Changchun, Jilin, China
Linyi Cancer Hospital
🇨🇳Linyi, Shandong, China
Shanghai General Hospital
🇨🇳Shanghai, Shanghai, China