A Study to Determine the Safety, Tolerability and Pharmacokinetics of an Anti-PD-1 Monoclonal Antibody in Subjects With Advanced Malignancies

Overview

About this study

The primary purpose of this study is to assess the safety and tolerability of TAB001 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 TAB001, 2) evaluate antitumor activity of TAB001; 3) determine the immunogenicity of TAB001 , and 4) evaluate pharmacodynamic effects of TAB001 on its target receptor, programmed cell death 1 (PD-1), as well as effects on the immune system. The exploratory objectives are to: 1) evaluate biomarkers that may correlate with activity of TAB001, 2) evaluate the utility of PD-L1 & additional exploratory markers as biomarkers that could aid in selection of appropriate subjects for TAB001 therapy, and 3) identification of additional biomarkers correlating with response to treatment with TAB001.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria: 

  • Signed Informed Consent Form.
  • Age ≥ 18 years.
  • Subject meets the following corresponding requirements for the part of the study they will enroll into:
    • During Part A, subjects must have a histologically or cytologically documented, incurable or metastatic solid tumor that has progressed on (or they have been intolerant to) standard systemic therapy options for their tumor type in the metastatic setting or must have a tumor type for which no such standard systemic option exists.
    • During Part B, subjects must have a histologically or cytologically documented diagnosis of esophageal or gastric carcinoma, cholangiocarcinoma, neuroendocrine tumor (NET) of the gastrointestinal tract and pancreas, sarcomas, both soft tissue sarcoma (excluding leiomyosarcoma) and chondrosarcoma, or with agreement of the Sponsor, other tumors (including NPC and HCC) that have been treated with 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. Patients with MSI-H/dMMR tumors are eligible to enroll:
      • Subjects with nasopharyngeal cancer must have received (or been intolerant to) 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) 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 RECISTv1.1 and irRECIST.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  • Adequate organ and marrow function, as defined below:
    • Hemoglobin ≥ 8.0 g/dL within first 2 weeks prior to first dose of toripalimab;
    • Absolute neutrophil count (ANC) ≥ 1.2 x 10^9/L (1,200/mm^3);
    • Platelet count ≥ 75 x 10^9/L (75,000/mm^3);
    • Total bilirubin ≤ 1.5 × upper limit of normal (ULN) except subjects with documented Gilbert’s syndrome who must have a baseline total bilirubin ≤ 3.0 mg/dL;
    • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN; for subjects with hepatic metastases, ALT and AST ≤ 5 × ULN;
    • Serum creatinine ≤ 1.5 × ULN OR calculated creatinine clearance (CrCl) or 24-hour urine CrCl ≥ 40 mL/minute;
    • Cockcroft-Gault formula will be used to calculate CrCl.(9.4); 24-hour urine CrCl will be derived using the measured creatinine clearance formula (9.5);
    • International normalized ratio (INR) and activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN; applies only to subjects who do not receive therapeutic anticoagulation; subjects receiving therapeutic anticoagulation (such as low-molecular weight heparin or warfarin) should be on a stable dose.
  • Willingness to provide consent for biopsy samples (In Part A, fresh pre-treatment biopsies will be requested from subjects with safely accessible lesions. For subjects who cannot provide a fresh pre-treatment biopsy, an archival specimen will be required. In Part B, fresh pre-treatment biopsies will be required from subjects with safely accessible lesions. Archival specimens will be requested).
  • Females of childbearing potential who are sexually active with a nonsterilized male partner must use effective contraception from time of screening, and must agree to continue using such precautions for 90 days after the final dose of toripalimab; cessation of birth control after this point should be discussed with a responsible physician. Periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of birth control. Females of childbearing potential are defined as those who are not surgically sterile (i.e., bilateral tubal  ligation, bilateral oophorectomy, or complete hysterectomy) or postmenopausal (defined as at least 12 months with no menses confirmed by follicle-stimulating hormone [FSH] levels. FSH testing will be conducted at the Screening visit to confirm post-menopausal status).
  • Subjects must use effective contraception as described in below:
    • Barrier Methods
      • Male condom plus spermicide;
      • Copper T intrauterine device;
      • Levonorgestrel-releasing intrauterine system;
      • (e.g., MirenaR)*
      • * this is also considered a hormonal method.
    • Hormonal Methods
      • Implants;
      • Hormone shot or injection;
      • Combined pill;
      • Minipill;
      • Patch.
  • Nonsterilized males who are sexually active with a female partner of childbearing potential must use effective contraception from Day 1 and for 90 days after receipt of the final dose of toripalimab.

Exclusion Criteria: 

  • Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or the follow-up period of an interventional study.
  • Any concurrent chemotherapy, radiotherapy, immunotherapy, or biologic therapy for cancer treatment. Concurrent use of hormones for non-cancer-related conditions (e.g., insulin for diabetes and hormone replacement therapy) is acceptable.
    • NOTE: Local treatment of isolated lesions for palliative intent is acceptable (e.g., by local surgery or radiotherapy).
  • Receipt of any investigational anticancer therapy within 4 weeks prior to the first dose of toripalimab.
  • Current or prior use of immunosuppressive medication within 4 weeks prior to the first dose of toripalimab, with the exception of intranasal and inhaled corticosteroids or systemic corticosteroids not to exceed 10 mg/day of prednisone or equivalent.
  • In 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.
  • In Part B: Exclusion of prior immunotherapy exposure will be limited to anti-PD-1, anti-PD-L1, or anti-PD-L2.
  • Prior allogeneic bone marrow transplantation or prior solid organ transplantation.
  • Major surgery (as defined by the investigator) within 4 weeks prior to first dose of toripalimab or still recovering from prior surgery.
  • Unresolved toxicities from prior anticancer therapy, defined as having not resolved to baseline or to NCI-CTCAE v4.03 Grade 0 or 1, or to levels dictated in the inclusion/exclusion criteria with the exception of alopecia. Subjects with irreversible toxicity that is not reasonably expected to be exacerbated by toripalimab may be included (e.g., hearing loss) after consultation with the medical monitor.
  • Active or prior documented autoimmune disease within the past 2 years.
    • NOTE: Subjects with vitiligo, Grave’s disease, or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded.
  • Known history of tuberculosis.
  • Subjects who are known to be human immunodeficiency virus (HIV) positive.
  • Subjects with evidence of hepatitis B or C virus infection, unless their hepatitis is considered to have been cured. (Note that subjects with prior hepatitis B virus [HBV] infection must have HBV viral load [VL] <100 IU/mL before study enrollment, and must be treated according to local standards; hepatitis C virus [HCV] infection must have, before study enrollment, no detectable VL and must be treated according to local standards).
  • Active or prior documented inflammatory bowel disease (e.g., Crohn’s disease, ulcerative colitis).
  • History of primary immunodeficiency.
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure according to New York Heart Association (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 AEs from toripalimab, or compromise the ability of the subject to give written informed consent.
  • 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.
  • Receipt of live attenuated vaccination within 4 weeks prior to study entry or within 4 weeks of receiving toripalimab.
  • Any condition that, in the opinion of the investigator or sponsor, would interfere with evaluation of toripalimab or interpretation of subject safety or study results.
  • Pregnant or breastfeeding women.

 

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Scottsdale/Phoenix, Ariz.

Mayo Clinic principal investigator

Amit Mahipal, M.B.B.S.

Contact us for the latest status

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

Jacksonville, Fla.

Mayo Clinic principal investigator

Amit Mahipal, M.B.B.S.

Contact us for the latest status

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

Rochester, Minn.

Mayo Clinic principal investigator

Amit Mahipal, M.B.B.S.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

More information

Publications

Publications are currently not available

Study Results Summary

Not yet available

Supplemental Study Information

Not yet available

Additional contact information

Cancer-related trials contact form

Phone: 855-776-0015 (toll-free)

International patient clinical studies questions