Clinical Trials /

Phase 1 Study of CI-8993 Anti-VISTA Antibody in Patients With Advanced Solid Tumor Malignancies

NCT04475523

Description:

This is a phase 1, open-label, multicenter dose-escalation study to determine the RP2D of CI 8993 for administration to patients with relapsed/refractory solid tumors by evaluating the safety and tolerability and characterizing the PK, PD, and anti cancer activity of CI-8993 in this population.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Phase 1 Study of CI-8993 Anti-VISTA Antibody in Patients With Advanced Solid Tumor Malignancies
  • Official Title: Phase 1 Study of CI-8993 Anti-VISTA Antibody in Patients With Advanced Solid Tumor Malignancies

Clinical Trial IDs

  • ORG STUDY ID: CI-8993-101
  • NCT ID: NCT04475523

Conditions

  • Solid Tumor

Interventions

DrugSynonymsArms
CI-8993CI-8993 dose escalation

Purpose

This is a phase 1, open-label, multicenter dose-escalation study to determine the RP2D of CI 8993 for administration to patients with relapsed/refractory solid tumors by evaluating the safety and tolerability and characterizing the PK, PD, and anti cancer activity of CI-8993 in this population.

Detailed Description

      The plan is to enroll approximately 50 patients with metastatic or unresectable solid tumor
      malignancy (non-lymphoma) that is considered relapsed and/or refractory to prior therapy into
      specific dose cohorts to determine the maximum tolerated dose (MTD) of full doses of CI-8993,
      based on the occurrence of dose limiting toxicities (DLTs) 28 days from the first full dose.
      Administration is every 2 weeks. To assure patient safety, each patient will receive an
      initial low dose of CI-8993 (step-dose) one week prior to their first full dose.

      A Safety Review Committee (SRC) will review all safety data and make cohort
      escalation/de-escalation decisions.
    

Trial Arms

NameTypeDescriptionInterventions
CI-8993 dose escalationExperimentalPatients will be administered CI-8993 intravenously at a planned infusion rate over 2 hours at planned step-doses and subsequent full doses. The planned schedule of administration is every 2 weeks. The MTD of full doses of CI-8993 will be determined based on the occurrence of DLTs 28 days from the first full dose. Eligible patients may receive CI-8993 at the dose and schedule, according to their assigned cohorts, until disease progression or unacceptable toxicity.
  • CI-8993

Eligibility Criteria

        Inclusion Criteria:

          1. Patient must be ≥18 years of age

          2. Patients must have the following disease related criteria:

               -  any type of solid tumor malignancy (non-lymphoma) that is metastatic or
                  unresectable and considered relapsed and/or refractory to prior therapy

               -  must have evaluable disease.

               -  Archival formalin-fixed, paraffin-embedded (FFPE) tumor tissue

          3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

          4. Adequate organ and bone marrow function, in the absence of growth factors.

          5. Fertility criteria:

               -  Women of childbearing potential (WOCBP) and fertile males with WOCBP partners
                  must use highly effective contraception

               -  Women must agree not to donate eggs (ova, oocytes) for the purposes of assisted
                  reproduction

               -  Men must agree not to donate sperm

               -  A man who is sexually active with a woman of childbearing potential and has not
                  had a vasectomy must agree to use a highly effective method of birth control.

          6. Patient must be willing and able to adhere to the prohibitions and restrictions
             specified in the protocol. Due to the possibility of neurologic events, patient must
             agree to refrain from driving or engaging in hazardous occupations or activities such
             as operating heavy or dangerous machinery during the first cycle of treatment.

          7. Each patient must sign an informed consent form (ICF) indicating that he or she
             understands the purpose and procedures required for the study and is willing to
             participate in the study.

          8. Patient must have central venous access, such as port-a-cath, or peripherally inserted
             central catheter for at least the first cycle of treatment.

        Exclusion Criteria:

          1. Patient has any of the following medical situations:

               -  Uncontrolled intercurrent illness including, but not limited to: poorly
                  controlled hypertension; poorly controlled diabetes; ongoing active infection
                  requiring antibiotics or acute infectious illness (including suspected viral
                  infection); symptomatic congestive heart failure; unstable angina pectoris;
                  cardiac arrhythmia considered to increase risk for the patient by the
                  Investigator; psychiatric illness that would limit compliance with study
                  requirement

               -  Medical illness requiring systemic glucocorticoid use > 10mg/day prednisone
                  equivalent.

               -  Patients with history of brain metastasis

               -  Personal or familial history of hemophagocytic lymphohistiocytosis or macrophage
                  activation syndrome

               -  An autoimmune disease with a history of flares requiring immunosuppressant
                  medications within the past 6 months

               -  History of known or suspected seizure disorder

               -  Prior allogeneic organ or bone marrow transplant (BMT).

               -  Social situation that would limit compliance with study requirements

               -  Major surgery (eg, requiring general anesthesia) within 4 weeks before the
                  planned first dose of study drug, or not fully recovered from prior surgery, or
                  has surgery planned during the time the patient is expected to participate in the
                  study or within 4 weeks after the last dose of study drug.

               -  History of positive testing for hepatitis B surface antigen (HBsAg) or hepatitis
                  C antibody (anti-hepatitis C virus) or other clinically active liver disease, or
                  positive testing at screening for HBsAg or anti- hepatitis C virus.

               -  History of human immunodeficiency virus (HIV) antibody positive

          2. Patient has had prior therapy meeting the following:

               -  Anticancer immunotherapy within 3 weeks prior to the first dose of CI-8993

               -  Prior T Cell Receptor-modified or chimeric antigen receptor T cell (CART) therapy

               -  Other anticancer therapy, including chemotherapy, targeted therapy, or treatment
                  with an investigational anticancer agent within 2 weeks prior to the first dose
                  of CI-8993

               -  Radiotherapy (excluding limited palliative radiation) within 2 weeks of start of
                  CI-8993

               -  Unresolved toxicities from previous anticancer therapies above Grade 1.

               -  Immune-related AE with prior immunotherapy that was Grade 3 or higher.

               -  Patient has known allergies, hypersensitivity, or intolerance to components of CI
                  8993

          3. Patient receiving therapeutic anticoagulants

          4. Fertility exclusions:

               -  Patient is pregnant, breastfeeding, or planning to become pregnant while enrolled
                  in this study or within 3 months after the last dose of study drug; WOCBP must
                  have a negative pregnancy status confirmed by serum pregnancy test at screening
                  and within 72 hours of first dose of study drug.

               -  Patient is a man who plans to father a child while enrolled in this study or
                  within 3 months after the last dose of study drug.

          5. Vaccinated with a live vaccine within 28 days (with the exception of the annual
             inactivated influenza vaccine) prior to the first dose of study drug
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:To determine the maximum tolerated dose of CI-8993
Time Frame:2 years
Safety Issue:
Description:The highest dose at a schedule, at which the DLT rate during the first cycle of this study (28 days from the first full dose) is < 33% in at least 6 patients.

Secondary Outcome Measures

Measure:To characterize the pharmacokinetic (PK) parameters of CI-8993 measured by Cmax
Time Frame:6 months
Safety Issue:
Description:maximum serum concentration (Cmax)
Measure:To characterize the pharmacokinetic (PK) parameters of CI-8993 measured by Cmin
Time Frame:6 months
Safety Issue:
Description:trough serum concentration (Cmin)
Measure:To characterize the pharmacokinetic (PK) parameters of CI-8993 measured by Tmax
Time Frame:6 months
Safety Issue:
Description:Time to maximum serum concentration
Measure:To characterize the pharmacokinetic (PK) parameters of CI-8993 measured by Area under the concentration versus time curve (AUC)
Time Frame:6 months
Safety Issue:
Description:area under the concentration-time curve
Measure:To characterize the pharmacokinetic (PK) parameters of CI-8993 measured by T 1/2
Time Frame:6 months
Safety Issue:
Description:Serum terminal elimination half-life (T 1/2)
Measure:To characterize the pharmacokinetic (PK) parameters of CI-8993 measured by volume of distribution at steady state
Time Frame:6 months
Safety Issue:
Description:volume of distribution at steady state (Vdss)
Measure:To characterize the pharmacokinetic (PK) parameters of CI-8993 measured by clearance
Time Frame:6 months
Safety Issue:
Description:Clearance (CL)
Measure:To assess anti-drug antibodies (ADA) of CI-8993
Time Frame:6 months
Safety Issue:
Description:Evaluate antibodies to CI-8993 in serum

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Curis, Inc.

Last Updated

July 14, 2020