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
  • Non-Small Cell Lung Carcinoma
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 (AMBER)
  • 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 (AMBER)

Clinical Trial IDs

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

Conditions

  • Advanced or Metastatic Solid Tumors

Interventions

DrugSynonymsArms
TSR-022TIM 3Part 1- Dose Escalation
TSR-042, an anti-PD-1 antibodyPD-1Part 1- Dose Escalation
TSR-033, an anti-LAG-3 antibodyLag3Part 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. 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 {currently closed to enrollment} 1b: Dose escalation TSR-022 in combination with an anti-PD-1 antibody (nivolumab) {currently closed to enrollment} 1c: TSR-022 dose in combination with an anti-PD-1 antibody (TSR-042) {currently closed to enrollment} 1d: Dose escalation TSR-022 in combination with an anti-PD-1 antibody (TSR-042) and an anti-LAG-3 antibody (TSR-033) 1e: TSR-022 in combination with an anti-PD-1 antibody in specific tumor types who have not received prior immunotherapy
  • TSR-022
  • TSR-042, an anti-PD-1 antibody
  • TSR-033, an anti-LAG-3 antibody
Part 2- Expansion CohortsExperimentalPart 2 of the study will evaluate the anti-tumor activity of TSR-022, in combination with TSR-042 and as monotherapy as deemed necessary. Cohort A: anti-PD-1 treated melanoma (currently closed to enrollment), Cohort B: anti-PD-1 treated NSCLC (currently closed to enrollment) Cohort C: (CRC) no more than 3 lines of prior therapy (currently closed to enrollment) Cohort D: NSCLC with no more than 2 lines of prior therapy
  • TSR-022
  • TSR-042, an 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 pregnancy test or be of non-childbearing
             potential.

          -  Required that female patients of childbearing potential use a highly effective of
             contraception with their partner

          -  Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1 with adequate
             hematologic and 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 3 weeks prior to initiation of study
             treatment depending on study part

          -  Prior treatment with an anti-PD-1, anti-PD-L1, anti-TIM-3 or anti-LAG-3 (Part 1e)

          -  Prior treatment with an anti-LAG-3 or anti-TIM-3 (Part 2)

          -  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 150 days after the
             last dose of study treatment

          -  History of human immunodeficiency virus (HIV), pneumonitis, 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

          -  Patients with radiologic or clinical progression ≤ 8 weeks after initiation of a prior
             anti-PD-1 or anti-PD-L1 antibody (Cohort 2D)

          -  Patients with known EGFR mutation, ALK translocation or ROS1 mutation (Cohort 2D)
      
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:
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:Immunogenicity as assessed by the presence of anti-drug antibodies
Time Frame:Part 1 and 2 -Approximately 4 years
Safety Issue:
Description:
Measure:Maximum plasma concentration (Cmax) of TSR-022
Time Frame:Part 1 - Approximately 9 months
Safety Issue:
Description:
Measure:Minimum plasma concentration (Cmin) of TSR-022
Time Frame:Part 1 - Approximately 9 months
Safety Issue:
Description:
Measure:Area under the curve (AUC),0-infinity of TSR-022
Time Frame:Part 1 - Approximately 9 months
Safety Issue:
Description:
Measure:Area under the curve at steady state (AUC,ss) of TSR-022
Time Frame:Part 1 - Approximately 9 months
Safety Issue:
Description:
Measure:Maximum plasma concentration at steady state (Cmax,ss) of TSR-022
Time Frame:Part 1 - Approximately 9 months
Safety Issue:
Description:
Measure:Minimum plasma concentration at steady state (Cmin,ss) of TSR-022
Time Frame:Part 1 - Approximately 9 months
Safety Issue:
Description:
Measure:Maximum plasma concentration (Cmax) of TSR-042
Time Frame:Part 1 - Approximately 9 months
Safety Issue:
Description:
Measure:Minimum plasma concentration (Cmin) of TSR-042
Time Frame:Part 1 - Approximately 9 months
Safety Issue:
Description:
Measure:Area under the curve (AUC),0-infinity of TSR-042
Time Frame:Part 1 - Approximately 9 months
Safety Issue:
Description:
Measure:Area under the curve at steady state (AUC,ss) of TSR-042
Time Frame:Part 1 - Approximately 9 months
Safety Issue:
Description:
Measure:Maximum plasma concentration at steady state (Cmax,ss) of TSR-042
Time Frame:Part 1 - Approximately 9 months
Safety Issue:
Description:
Measure:Minimum plasma concentration at steady state (Cmin,ss) of TSR-042
Time Frame:Part 1 - Approximately 9 months
Safety Issue:
Description:
Measure:Maximum plasma concentration (Cmax) of TSR-033
Time Frame:Part 1 - Approximately 9 months
Safety Issue:
Description:
Measure:Minimum plasma concentration (Cmin) of TSR-033
Time Frame:Part 1 - Approximately 9 months
Safety Issue:
Description:
Measure:Area under the curve (AUC),0-infinity of TSR-033
Time Frame:Part 1 - Approximately 9 months
Safety Issue:
Description:
Measure:Area under the curve at steady state (AUC,ss) of TSR-033
Time Frame:Part 1 - Approximately 9 months
Safety Issue:
Description:
Measure:Maximum plasma concentration at steady state (Cmax,ss) of TSR-033
Time Frame:Part 1 - Approximately 9 months
Safety Issue:
Description:
Measure:Minimum plasma concentration at steady state (Cmin,ss) of TSR-033
Time Frame:Part 1 - Approximately 9 months
Safety Issue:
Description:
Measure:Maximum plasma concentration (Cmax) of nivolumab
Time Frame:Part 1 - Approximately 9 months
Safety Issue:
Description:
Measure:Minimum plasma concentration (Cmin) of nivolumab
Time Frame:Part 1 - Approximately 9 months
Safety Issue:
Description:
Measure:Area under the curve (AUC),0-infinity of nivolumab
Time Frame:Part 1 - Approximately 9 months
Safety Issue:
Description:
Measure:Area under the curve at steady state (AUC,ss) of nivolumab
Time Frame:Part 1 - Approximately 9 months
Safety Issue:
Description:
Measure:Maximum plasma concentration at steady state (Cmax,ss) of nivolumab
Time Frame:Part 1 - Approximately 9 months
Safety Issue:
Description:
Measure:Minimum plasma concentration at steady state (Cmin,ss) of nivolumab
Time Frame:Part 1 - Approximately 9 months
Safety Issue:
Description:

Details

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

Trial Keywords

  • Antibodies
  • TSR-022
  • Advanced solid tumors
  • Metastatic solid tumors
  • Immunotherapy
  • PD-1
  • Anti-PD-1
  • colorectal cancer
  • non-small cell lung cancer
  • Melanoma
  • Anti-LAG-3
  • TSR-033
  • TSR-042

Last Updated

October 30, 2019