Principal Investigator
Enrollment Status
Clinical Trial ID
Clinical Trial Summary
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.
Phase
Phase 1
Funding Agency/Sponsor
Industrial
Disease
Stomach and Esophageal Cancer
Enrollment Eligibility
Inclusion Criteria:
- 1. Willing to sign Informed Consent;
- 2. 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;
- 3. 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.
1. Subjects with NPC must have received, or been intolerant to, a platinum-based
combination as part of their prior therapy for advanced/metastatic disease;
2. 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;
3. 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;
4. 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;
5. Subjects with HCC must have received (or been intolerant to) sorafenib as part of
their prior therapy for advanced metastatic disease.
- 4. Measurable disease per RECIST v1.1 and irRECIST;
- 5. ECOG performance status of 0 or 1;
- 6. Adequate organ and marrow function;
- 7. Willingness to provide consent for biopsy samples;
- 8. For females of childbearing potential, use effective contraception from time of
screening though 90 days post last dose of Toripalimab.
Exclusion Criteria:
- 1. Concurrent enrollment in another clinical study, unless it is an observational
(non-interventional) clinical study or the follow-up period of an interventional
study;
- 2. Any concurrent chemotherapy, radiotherapy, immunotherapy, or biologic therapy for
cancer treatment. Concurrent use of hormones for non-cancer related conditions is
acceptable (e.g., insulin for diabetes & hormone replacement therapy). Local treatment
of isolated lesions for palliative intent is acceptable;
- 3. Receipt of any investigational anti-cancer therapy within 4 weeks prior to first
dose of Toripalimab;
- 4. Current use or prior use of immunosuppressive medication within 4 weeks prior to
first dose of Toripalimab, with the exception of intranasal and inhaled
corticosteroids or systemic corticosteroids not to exceed 10mg/day of prednisone or
equivalent;
- 5. Part A: Prior exposure to immunotherapy such as but not limited to other
anti-CTLA-4, anti-PD-1, or anti-PD-L1 antibodies excluding vaccines. Part B: Exclusion
of prior immunotherapy exposure will be limited to anti-PD-1, anti-PD-L1, or
anti-PD-L2;
- 6. Prior allogeneic bone marrow transplantation or prior solid organ transplantation;
- 7. Major surgery within 4 weeks prior to first dose of Toripalimab or still recovering
from prior surgery;
- 8. Unresolved toxicities from prior anticancer therapy defined as having not resolved
to baseline or to Grade 0 or 1, or to levels dictated in the inclusion/exclusion
criteria with the exception of alopecia;
- 9. Active or prior documented autoimmune disease within the past 2 years. Subjects
with vitiligo, Grave's disease, or psoriasis not requiring systemic treatment within
the past 2 years are not excluded;
- 10. Known history of tuberculosis;
- 11. Known to be human immunodeficiency virus (HIV) positive, hepatitis B, or hepatitis
C positive;
- 12. Active or prior documented inflammatory bowel disease (e.g., Crohn's disease,
ulcerative colitis);
- 13. History of primary immunodeficiency;
- 14. Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure according to NYHA Functional
Classification ≥3, uncontrolled hypertension, unstable angina pectoris, cardiac
arrhythmia, active peptic ulcer disease or gastritis, or psychiatric illness/social
situations that would limit compliance with study requirements, substantially increase
risk of incurring adverse events from Toripalimab, or compromise the ability of the
subject to give written informed consent;
- 15. Symptomatic or untreated central nervous system metastases requiring concurrent
treatment, inclusive of but not limited to surgery, radiation, and/or corticosteroids.
Subjects with previously treated brain metastases may participate provided they are
clinically stable for at least 4 weeks prior to study entry, have no evidence of new
or enlarging metastases, and are off steroids;
- 16. Receipt of live attenuated vaccination within 30 days prior to study entry or
within 4 weeks of receiving Toripalimab;
- 17. Pregnancy or breastfeeding women.