Clinical Trials /

TSR-022 (Anti-TIM-3 Antibody) and TSR-042 (Anti-PD-1 Antibody) in Patients With Liver Cancer

NCT03680508

Description:

TSR-022 and TSR-042 may stop the growth of tumor cells by allowing the immune system to attack the cancer. This phase II trial is studying how well TSR-022 and TSR-044 work in combination in treating patients with locally advanced or metastatic liver cancer.

Related Conditions:
  • Hepatocellular Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: TSR-022 (Anti-TIM-3 Antibody) and TSR-042 (Anti-PD-1 Antibody) in Patients With Liver Cancer
  • Official Title: Phase II Study of TSR-022 in Combination With TSR-042 for the Treatment of Advanced Hepatocellular Carcinoma

Clinical Trial IDs

  • ORG STUDY ID: ACOBA-2017-2
  • NCT ID: NCT03680508

Conditions

  • Adult Primary Liver Cancer
  • Advanced Adult Primary Liver Cancer
  • Localized Unresectable Adult Primary Liver Cancer

Interventions

DrugSynonymsArms
TSR-022 and TSR-042Anti-TIM-3 Antibody, Anti-PD-1 AntibodyTSR-022 and TSR-042

Purpose

TSR-022 and TSR-042 may stop the growth of tumor cells by allowing the immune system to attack the cancer. This phase II trial is studying how well TSR-022 and TSR-044 work in combination in treating patients with locally advanced or metastatic liver cancer.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To assess the objective response rate (ORR) as determined by RECIST v1.1 of advanced
      hepatocellular cancer (HCC) patients treated with TSR-022 and TSR-042.

      SECONDARY OBJECTIVES:

      I. To determine the ORR as determined by the immune related Response Criteria (irRC),
      duration of response (DOR), time to progression (TTP), progression free survival (PFS),
      overall survival (OS), and alpha-fetoprotein (AFP) response of study participants.

      II. To evaluate the safety profile of treated patients.

      OUTLINE:

      Patients receive TSR-022 and TSR-042 on day 1. Courses repeat every 21 days in the absence of
      disease progression or unacceptable toxicity.

      Patients are followed every 9 weeks.
    

Trial Arms

NameTypeDescriptionInterventions
TSR-022 and TSR-042ExperimentalPatients receive TSR-022 (Anti-TIM-3 Antibody) and TSR-042 (Anti-PD-1 Antibody) via IV day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
  • TSR-022 and TSR-042

Eligibility Criteria

        Inclusion Criteria:

          -  Histologically or cytologically confirmed hepatocellular cancer

          -  Barcelona Clinic Liver Cancer Stage B or C

          -  Cirrhosis grade of Child-Pugh class A or B7

          -  Subjects with HBV infection are required to be receiving effective antiviral therapy
             and have a viral load less than 100 IU/mL. Antiviral therapy is not required for
             subjects with HCV infection

          -  Have at least one tumor lesion that can be accurately measured according to Response
             Evaluation Criteria in Solid Tumor (RECIST v1.1)

          -  No prior systemic therapy for HCC

          -  Age ≥ 18 years

          -  ECOG performance status 0-1

          -  Resolved acute effects of any prior therapy to baseline or Grade ≤1 NCI CTCAE

          -  Have adequate hematologic and renal function

          -  Prior local therapy, such as surgery, radioembolization, chemoembolization, or
             radiofrequency ablation is allowed if the index lesion(s) remains outside of the
             treatment field or has progressed since prior treatment

          -  Participant must be able to understand the study procedures and agree to participate
             in the study by providing written informed consent.

        Exclusion Criteria:

          -  Participant must not be simultaneously enrolled in any interventional clinical trial

          -  Participant must not have had major surgery ≤ 3 weeks prior to initiating protocol
             therapy and participant must have recovered from any surgical effects

          -  Participants must not have received investigational therapy ≤4 weeks, or within a time
             interval less than at least 5 half-lives of the investigational agent, whichever is
             shorter, prior to initiating protocol therapy.

          -  Active or untreated central nervous system (CNS) and leptomeningeal metastases are
             excluded

          -  Prior therapy with any medication targeting PD-1, PD-L1, or TIM-3

          -  Participant must not have a known hypersensitivity to TSR-042 and TSR-022 components
             or excipients.

          -  Participants with active malignancy (other than HCC) or a prior malignancy within the
             past 2 years are excluded. Participants with completely resected cutaneous melanoma
             (early stage), basal cell carcinoma, cutaneous squamous cell carcinoma, cervical
             carcinoma in-situ, breast carcinoma in-situ, and localized prostate cancer are
             eligible

          -  Participant must not have serious, uncontrolled medical disorder, or nonmalignant
             systemic disease. Examples include, but are not limited to uncontrolled ventricular
             arrhythmia, uncontrolled major seizure disorder, unstable spinal cord compression, or
             superior vena cava syndrome.

          -  Known history of Human Immunodeficiency Virus (HIV) infection

          -  Participant has an active autoimmune disease that has required systemic treatment in
             the past 2 years (.ie., with use of disease-modifying agents, corticosteroids, or
             immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or
             physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency,
             etc.) is not considered a form of systemic treatment.

          -  History of idiopathic pulmonary fibrosis, interstitial lung disease, bronchial asthma,
             organizing pneumonia, bronchiolitis obliterans, drug-induced pneumonitis, or
             idiopathic pneumonitis

          -  History of organ transplantation including allogeneic bone marrow transplantation

          -  Participant has a diagnosis of immunodeficiency or has receiving systemic steroid
             therapy or any other form of immunosuppressive therapy within 7 days prior to
             initiating protocol therapy.

          -  Psychiatric illness/social situations that would limit compliance with study
             requirements

          -  Pregnant, lactating, breastfeeding, or intending to become pregnant during the study
             and for 180 days after the study
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective Response
Time Frame:From date of treatment until the date of best documented response, assessed up to 36 months
Safety Issue:
Description:Determined by RECIST v1.1 criteria

Secondary Outcome Measures

Measure:Objective Response (irRC)
Time Frame:From date of treatment until the date of best documented response, assessed up to 36 months
Safety Issue:
Description:Objective response as determined by the immune related Response Criteria
Measure:Duration of Response
Time Frame:From date of treatment until the date of progression, assessed up to 36 months
Safety Issue:
Description:Time from tumor response to progression
Measure:Time to progression
Time Frame:From date of treatment until the date of progression, assessed up to 36 months
Safety Issue:
Description:Time from treatment to progression of cancer
Measure:Progression free survival
Time Frame:From date of treatment until the date of progression or death, assessed up to 36 months
Safety Issue:
Description:Time from treatment to progression of cancer or death
Measure:Overall survival
Time Frame:From date of treatment until the date of death, assessed up to 36 months
Safety Issue:
Description:Time from treatment to death
Measure:AFP response
Time Frame:From treatment start to documentation of AFP progression, assessed up to 36 months.
Safety Issue:
Description:Percentage of AFP decrease from baseline to nadir
Measure:Incidence of Treatment-Emergent Adverse Events as assessed by CTCAE v4.0
Time Frame:From treatment until cessation of study treatment and resolution of adverse events, assessed up to 36 months
Safety Issue:
Description:Tabulation of adverse events, CTCAE v4.0

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:University of Hawaii

Trial Keywords

  • immunotherapy
  • PD-1
  • TIM-3

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