Study of JS001 in Participants With Advanced Solid Tumors
Condition: Solid Tumors
MeSH terms: Neoplasms
Study type: Interventional
Phase: Phase 1

Summary: 
      The purpose of this study is to evaluate the safety, tolerance and Dose-Limiting Toxicity
      (DLT) of Recombinant humanized anti-PD-1 monoclonal antibody (JS001) in patients with
      advanced solid tumors.
    

Detailed description: 
      OVERVIEW

      This is a Phase 1, open-label, dose-escalation study of JS-001, a humanized monoclonal IgG4
      antibody targeting the Programmed Death -1 (PD-1). It is estimated that 12-24 subjects with
      advanced or recurrent solid tumors or will be enrolled in the study.

      A 3+3 design will be utilized for this Phase 1 study. Four dose levels are planned and
      include: 0.3, 1, 3, 10 mg/kg/dose. Each of the 4 dose levels will use 2 dose schedules:
      single dose, repeated doses every 2 weeks. Subjects will be assigned to a dose schedule in
      the order of study entry.

      The study will be the traditional 3 + 3 design with 3 or 6 subjects treated at this dose
      level and at all subsequent dose levels depending upon the incidence of DLTs. If no DLTs
      occur in a cohort of 3 subjects, a new cohort of 3 subjects will be treated at the next
      higher dose level. If 1 of 3 subjects in a cohort experiences a DLT, that cohort will be
      expanded to 6 subjects. If only 1 of the 6 subjects has a DLT, then the next cohort of 3
      subjects will be treated at the next higher dose level. If 2 or more DLTs occur within a
      cohort, then that dose level will be above the MTD (the highest dose where no more than 1 of
      6 subjects has experienced a DLT), and the previous lower (tolerated) dose level will be
      considered the MTD.

      A DLT is defined as a Grade 3 drug-related adverse event occurring within the first cycle (28
      days) of dosing (excluding tumor flare defined as local pain, irritation, or rash localized
      at sites of known or suspected tumor or a transient Grade 3 infusion adverse event) using
      National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE)
      version 4.0 in a single dose cohort.

      Tumor response will be evaluated using immune-related response criteria (irRC), WHO criteria
      , Response Evaluation Criteria in Solid Tumors (RECIST), immune-related RECIST, and
      International Workshop to Standardize Response Criteria for non-Hodgkin's Lymphomas (for
      lymphomas only).

      In the absence of confirmed disease progression and intolerable toxicities, subjects in the
      single dose cohorts and multiple dose cohorts will be allowed to continue JS-001
      administration with the consent of the subject.

      DOSAGE AND ADMINISTRATION

      JS-001 will be administered as a 60-minute i.v. infusion. Cohorts will include escalating
      dose levels of 0.3, 1, 3, 10mg/kg/dose.

      SAFETY EVALUATIONS

      Assessment of safety will be determined by vital sign measurements, clinical laboratory
      tests, Eastern Cooperative Oncology Group (ECOG) performance status evaluations, diagnostic
      imaging, physical examinations, electrocardiograms, and the incidence and severity of adverse
      events.

      Safety will also include evaluations of immune safety and immunogenicity. Particular
      attention will be given to adverse events that may follow enhanced T-cell activation such as
      dermatitis and colitis, uveitis, or other immune-related adverse events (irAEs).

      An irAE is a clinically significant adverse event of any organ that is associated with drug
      exposure, of unknown etiology, and is consistent with an immune-mediated mechanism.

      EFFICACY EVALUATIONS

      The primary efficacy endpoint is the best response rate (RR). Duration of response,
      progression-free survival, time to progression, and overall survival will also be analyzed.

      PHARMACOKINETIC EVALUATIONS

      Pharmacokinetic parameters include AUC, Cmax, tmax, and t½, etc. STATISTICAL METHODS The
      sample size for this study is not determined from power analysis. It is based on the 3+3
      design for dose escalation and safety evaluation requirements.

      Descriptive statistics will include: mean, standard deviation, median, and minimum and
      maximum values for continuous variables; frequencies and percentages for categorical
      variables.

      The efficacy parameters will be summarized using descriptive statistics. All safety and
      pharmacokinetic parameters will be summarized using descriptive statistics.
    

Intervention name(s): humanized anti-PD-1 monoclonal antibody toripalimab
Intervention type(s): Biological
Intervention description(s): humanized anti-PD-1 monoclonal antibody (JS001) is a programmed death-1 (PD-1) immune checkpoint inhibitor antibody, which selectively interferes with the combination of PD-1 with its ligands, PD-L1 and PD-L2, resulting in the activation of lymphocytes and elimination of malignancy theoretically.
Other intervention name(s): JS001, TAB001
Intervention MeSH terms: Antibodies; Antibodies, Monoclonal
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: JS001; solid tumors