A Phase 1, Multicenter, Open-label Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of TAB001 in Subjects With Advanced Malignancies
The primary objective is to assess the safety and tolerability of Toripalimab in subjects with various advanced malignancies and to evaluate the recommended Phase 2 dose. The secondary objectives are to: 1) describe the pharmacokinetic (PK) profile of Toripalimab, 2) evaluate antitumor activity of Toripalimab; 3) determine the immunogenicity of Toripalimab; 4) evaluate overall survival. The exploratory objectives are to: 1) evaluate biomarkers that may correlate with activity of Toripalimab, 2) evaluate pharmacodynamic effects of Toripalimab on its target receptor, programmed cell death 1 (PD-1), as well as effects on the immune system. 3) evaluate the utility of PD-L1 \& additional exploratory markers as biomarkers that could aid in selection of appropriate subjects for TAB001 therapy, and 4) identification of additional biomarkers correlating with response to treatment with TAB001.
• Willing to sign Informed Consent;
• Part A, must have a histologically or cytologically documented, incurable, or metastatic solid tumor that has progressed on, or been intolerant to, all standard systemic therapy options for the tumor type in the metastatic setting, or must have a tumor type for which no such standard systemic option exists;
• Part B, must have a histologically or cytologically documented diagnosis of esophageal or gastric carcinoma, nasopharyngeal carcinoma (NPC), hepatocellular carcinoma (HCC), both soft tissue sarcoma (excluding leiomyosarcoma), chondrosarcoma, or with agreement of the sponsor, or other tumors who have received at least one line of standard systemic therapy for their respective tumor type in the metastatic setting with progressive locally advanced or metastatic disease that is not amenable to definitive local therapy with curative intent. Patient with MSI-H/dMMR Tumors are eligible to enroll.
‣ Subjects with NPC must have received, or been intolerant to, a platinum-based combination as part of their prior therapy for advanced/metastatic disease;
⁃ Subjects with soft tissue sarcoma and chondrosarcoma must have radiographic evidence of progression within the previous 6 months and must have received at least 1 line of systemic therapy;
⁃ Subjects with esophageal cancer must have received, or been intolerant to, a platinum-based combination as part of their prior therapy for advanced/metastatic disease;
⁃ Subjects with gastric cancer must have received, or been intolerant to, a fluoropyrimidine-platinum combination as part of their prior therapy for advanced/metastatic disease;
⁃ Subjects with HCC must have received (or been intolerant to) sorafenib as part of their prior therapy for advanced metastatic disease.
• Measurable disease per RECIST v1.1 and irRECIST;
• ECOG performance status of 0 or 1;
• Adequate organ and marrow function;
• Willingness to provide consent for biopsy samples;
• For females of childbearing potential, use effective contraception from time of screening though 90 days post last dose of Toripalimab.