The Study to Evaluate Toripalimab (JS001) in Patients With Advanced GC, ESCC, NPC, HNSCC

Summary

Participation Requirements

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 th...

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.

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