Clinical Trials /

A Phase 1 Study of TSR-022, an Anti-TIM-3 Monoclonal Antibody, in Patients With Advanced Solid Tumors (AMBER)

NCT02817633

Description:

This is a multicenter, open-label, first-in-human Phase 1 study evaluating the anti-TIM-3 (T cell immunoglobulin and mucin containing protein-3) antibody TSR-022, as a monotherapy and in combination with an anti-PD-1 antibody, in patients with advanced solid tumors. The study will be conducted in 2 parts: dose escalation and cohort expansion.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Phase 1 Study of TSR-022, an Anti-TIM-3 Monoclonal Antibody, in Patients With Advanced Solid Tumors
  • Official Title: A Phase 1 Dose Escalation and Cohort Expansion Study of TSR-022, an Anti-TIM-3 Monoclonal Antibody, in Patients With Advanced Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: 4020-01-001
  • NCT ID: NCT02817633

Conditions

  • Advanced or Metastatic Solid Tumors

Interventions

DrugSynonymsArms
TSR-022Part 1- Dose Escalation
anti-PD-1 antibodyPart 1- Dose Escalation

Purpose

This is a multicenter, open-label, first-in-human Phase 1 study evaluating the anti-TIM-3 (T cell immunoglobulin and mucin containing protein-3) antibody TSR-022, as a monotherapy and in combination with an anti-PD-1 antibody, in patients with advanced solid tumors who have limited available treatment options. The study will be conducted in 2 parts: dose escalation and cohort expansion.

Trial Arms

NameTypeDescriptionInterventions
Part 1- Dose EscalationExperimental1a: Dose escalation TSR-022 alone 1b: Dose escalation TSR-022 in combination with an anti-PD-1 antibody 1c: TSR-022 dose in combination with an anti-PD-1 antibody
  • TSR-022
  • anti-PD-1 antibody
Part 2- Expansion CohortsExperimentalPart 2 of the study will further explore the safety and clinical activity of TSR-022 as monotherapy and in combination with anti-PD-1 antibody in patients with select tumor types
  • TSR-022
  • anti-PD-1 antibody

Eligibility Criteria

        Partial Inclusion Criteria:

          -  Patient with advanced or metastatic solid tumor and has disease progression or
             treatment intolerance after treatment with available therapies

          -  Agreement to biopsies before and during treatment, depending on study part

          -  Female patients must have a negative serum pregnancy test or be of non-childbearing
             potential.

          -  Required that female patients of childbearing potential use two methods of
             contraception with their partner

          -  Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1 and adequate organ
             function

        Partial Exclusion Criteria:

          -  Received prior therapy with an anti-CTLA-4, anti-PD-1, anti-PD1-ligand-1 (anti-PD-L1),
             or anti-PD-1 ligand-2 (anti-PD-L2) agent within 8 weeks prior to initiation of study
             treatment depending on study part

          -  Known uncontrolled central nervous system (CNS) metastases and/or carcinomatous
             meningitis or known malignancy that progressed or required active treatment within the
             last 2 years

          -  Pregnant, breastfeeding, or expecting to conceive children within projected duration
             of study

          -  History of human immunodeficiency virus (HIV), interstitial lung disease, active
             Hepatitis B or Hepatitis C, or ≥Grade 3 immune-related AE with prior immunotherapy

          -  Autoimmune disease that required systemic treatment

          -  Not recovered from radiation and chemotherapy-induced AEs

          -  Participated in another investigational study (drug or device) within 4 weeks of first
             dose

          -  Received prior anticancer therapy within 21 days of first dose

          -  Not recovered from AEs and/or complications from major surgery prior to first dose

          -  Received a vaccine within 7 days of first dose
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Safety and tolerability of TSR-022 using Common Terminology Criteria for Adverse Events (CTCAE v.4.03) in patients with advanced solid tumors
Time Frame:Part 1 Dose Escalation - Approximately 2 years
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Safety and tolerability of TSR-022 using CTCAE v.4.03
Time Frame:Part 2 - Approximately 2 years
Safety Issue:
Description:Incidence of treatment-emergent AEs (TEAEs), SAEs, immune-related AEs (irAEs), TEAEs leading to death, and AEs leading to discontinuation occurring while patients are on treatment or up to 90 days after the last dose of study drug as assessed by CTCAE v4.03
Measure:Overall Response Rate (ORR) by RECIST v. 1.1 (Part 1)
Time Frame:Part 1 and Part 2 - Approximately 4 years
Safety Issue:
Description:
Measure:ORR by immune-related RECIST (irRECIST)
Time Frame:Part 1 and Part 2 - Approximately 4 years
Safety Issue:
Description:
Measure:Duration of response (DOR) by RECIST v 1.1
Time Frame:Part 1 and Part 2 - Approximately 4 years
Safety Issue:
Description:
Measure:Disease control rate (DCR) by RECIST v 1.1 and by irRECIST
Time Frame:Part 1 and Part 2 - Approximately 4 years
Safety Issue:
Description:
Measure:Progression-free survival (PFS) by RECIST v 1.1 and by irRECIST
Time Frame:Part 1 and Part 2 - Approximately 4 years
Safety Issue:
Description:
Measure:Overall survival (OS)
Time Frame:Part 1 and Part 2 - Approximately 4 years
Safety Issue:
Description:
Measure:PK Parameter: AUC, 0-last assessment
Time Frame:Part 1 and Part 2 - Approximately 4 years
Safety Issue:
Description:
Measure:PK Parameter: AUC, 0 to infinity
Time Frame:Part 1 and Part 2 - Approximately 4 years
Safety Issue:
Description:
Measure:PK Parameter: AUC at steady state
Time Frame:Part 1 and Part 2 - Approximately 4 years
Safety Issue:
Description:
Measure:PK Parameter: Minimum Concentration (Cmin)
Time Frame:Part 1 and Part 2 - Approximately 4 years
Safety Issue:
Description:
Measure:PK Parameter: Maximum Concentration (Cmax)
Time Frame:Part 1 and Part 2 - Approximately 4 years
Safety Issue:
Description:
Measure:PK Parameter: Clearance (CL)
Time Frame:Part 1 and Part 2 - Approximately 4 years
Safety Issue:
Description:
Measure:PK Parameter: Cmin at steady state (Cmin,ss)
Time Frame:Part 1 and Part 2 - Approximately 4 years
Safety Issue:
Description:
Measure:PK Parameter: Cmax at steady state (Cmax, ss)
Time Frame:Part 1 and Part 2 - Approximately 4 years
Safety Issue:
Description:
Measure:PK Parameter: Volume of Distribution (Vz)
Time Frame:Part 1 and Part 2 - Approximately 4 years
Safety Issue:
Description:
Measure:PK Parameter: terminal half-life (t1/2)
Time Frame:Part 1 and Part 2 - Approximately 4 years
Safety Issue:
Description:
Measure:Pharmacodynamic profile as assessed by receptor occupancy
Time Frame:Part 1 and 2 - Approximately 4 years
Safety Issue:
Description:
Measure:Immunogenicity as assessed by the presence of anti-drug antibodies
Time Frame:Part 1 and 2 -Approximately 4 years
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Tesaro, Inc.

Trial Keywords

  • Anitibodies
  • TSR-022
  • Advanced solid tumors
  • Metastatic solid tumors
  • Immunotherapy
  • PD-1
  • Anti-PD-1
  • colorectal cancer
  • non-small cell lung cancer
  • Melanoma

Last Updated

October 9, 2017