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Trial record 1 of 1 for:    02817633
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A Phase 1 Study of TSR-022, an Anti-TIM-3 Monoclonal Antibody, in Patients With Advanced Solid Tumors (AMBER)

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ClinicalTrials.gov Identifier: NCT02817633
Recruitment Status : Recruiting
First Posted : June 29, 2016
Last Update Posted : November 1, 2019
Sponsor:
Information provided by (Responsible Party):
Tesaro, Inc.

Tracking Information
First Submitted Date  ICMJE June 22, 2016
First Posted Date  ICMJE June 29, 2016
Last Update Posted Date November 1, 2019
Actual Study Start Date  ICMJE July 2016
Estimated Primary Completion Date June 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 7, 2019)
  • 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 ]
  • Anti-tumor activity of TSR-022 in patients with solid tumors, in terms of objective response rate (ORR) as assessed by the Investigators using Response Evaluation Criteria in Solid Tumors (RECIST) v. 1.1 [ Time Frame: Part 1e and Part 2 Expansion - Approximately 2 years ]
  • Recommended Phase 2 dose (RP2D) and schedule as monotherapy and in combination therapy [ Time Frame: Part 1 and Part 2 - Approximately 4 years ]
Original Primary Outcome Measures  ICMJE
 (submitted: June 24, 2016)
  • 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 ]
  • Anti-tumor activity of TSR-022 in patients with solid tumors, in terms of objective response rate (ORR) as assessed by the Investigators using Response Evaluation Criteria in Solid Tumors (RECIST) v. 1.1 [ Time Frame: Part 2 Expansion - Approximately 2 years ]
  • Recommended Phase 2 dose (RP2D) and schedule as monotherapy and in combination with an anti-PD-1 antibody [ Time Frame: Part 1 and Part 2 - Approximately 4 years ]
Change History Complete list of historical versions of study NCT02817633 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 7, 2019)
  • Safety and tolerability of TSR-022 using CTCAE v.4.03 [ Time Frame: Part 2 - Approximately 2 years ]
  • Overall Response Rate (ORR) by RECIST v. 1.1 (Part 1) [ Time Frame: Part 1 and Part 2 - Approximately 4 years ]
  • ORR by immune-related RECIST (irRECIST) [ Time Frame: Part 1 and Part 2 - Approximately 4 years ]
  • Duration of response (DOR) by RECIST v 1.1 [ Time Frame: Part 1 and Part 2 - Approximately 4 years ]
  • Disease control rate (DCR) by RECIST v 1.1 and by irRECIST [ Time Frame: Part 1 and Part 2 - Approximately 4 years ]
  • Progression-free survival (PFS) by RECIST v 1.1 and by irRECIST [ Time Frame: Part 1 and Part 2 - Approximately 4 years ]
  • Overall survival (OS) [ Time Frame: Part 1 and Part 2 - Approximately 4 years ]
  • Immunogenicity as assessed by the presence of anti-drug antibodies [ Time Frame: Part 1 and 2 -Approximately 4 years ]
  • Maximum plasma concentration (Cmax) of TSR-022 [ Time Frame: Part 1 - Approximately 9 months ]
  • Minimum plasma concentration (Cmin) of TSR-022 [ Time Frame: Part 1 - Approximately 9 months ]
  • Area under the curve (AUC),0-infinity of TSR-022 [ Time Frame: Part 1 - Approximately 9 months ]
  • Area under the curve at steady state (AUC,ss) of TSR-022 [ Time Frame: Part 1 - Approximately 9 months ]
  • Maximum plasma concentration at steady state (Cmax,ss) of TSR-022 [ Time Frame: Part 1 - Approximately 9 months ]
  • Minimum plasma concentration at steady state (Cmin,ss) of TSR-022 [ Time Frame: Part 1 - Approximately 9 months ]
  • Maximum plasma concentration (Cmax) of TSR-042 [ Time Frame: Part 1 - Approximately 9 months ]
  • Minimum plasma concentration (Cmin) of TSR-042 [ Time Frame: Part 1 - Approximately 9 months ]
  • Area under the curve (AUC),0-infinity of TSR-042 [ Time Frame: Part 1 - Approximately 9 months ]
  • Area under the curve at steady state (AUC,ss) of TSR-042 [ Time Frame: Part 1 - Approximately 9 months ]
  • Maximum plasma concentration at steady state (Cmax,ss) of TSR-042 [ Time Frame: Part 1 - Approximately 9 months ]
  • Minimum plasma concentration at steady state (Cmin,ss) of TSR-042 [ Time Frame: Part 1 - Approximately 9 months ]
  • Maximum plasma concentration (Cmax) of TSR-033 [ Time Frame: Part 1 - Approximately 9 months ]
  • Minimum plasma concentration (Cmin) of TSR-033 [ Time Frame: Part 1 - Approximately 9 months ]
  • Area under the curve (AUC),0-infinity of TSR-033 [ Time Frame: Part 1 - Approximately 9 months ]
  • Area under the curve at steady state (AUC,ss) of TSR-033 [ Time Frame: Part 1 - Approximately 9 months ]
  • Maximum plasma concentration at steady state (Cmax,ss) of TSR-033 [ Time Frame: Part 1 - Approximately 9 months ]
  • Minimum plasma concentration at steady state (Cmin,ss) of TSR-033 [ Time Frame: Part 1 - Approximately 9 months ]
  • Maximum plasma concentration (Cmax) of nivolumab [ Time Frame: Part 1 - Approximately 9 months ]
  • Minimum plasma concentration (Cmin) of nivolumab [ Time Frame: Part 1 - Approximately 9 months ]
  • Area under the curve (AUC),0-infinity of nivolumab [ Time Frame: Part 1 - Approximately 9 months ]
  • Area under the curve at steady state (AUC,ss) of nivolumab [ Time Frame: Part 1 - Approximately 9 months ]
  • Maximum plasma concentration at steady state (Cmax,ss) of nivolumab [ Time Frame: Part 1 - Approximately 9 months ]
  • Minimum plasma concentration at steady state (Cmin,ss) of nivolumab [ Time Frame: Part 1 - Approximately 9 months ]
Original Secondary Outcome Measures  ICMJE
 (submitted: June 24, 2016)
  • Safety and tolerability of TSR-022 using CTCAE v.4.03 [ Time Frame: Part 2 - Approximately 2 years ]
    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
  • Overall Response Rate (ORR) by RECIST v. 1.1 (Part 1) [ Time Frame: Part 1 and Part 2 - Approximately 4 years ]
  • ORR by immune-related RECIST (irRECIST) [ Time Frame: Part 1 and Part 2 - Approximately 4 years ]
  • Duration of response (DOR) by RECIST v 1.1 [ Time Frame: Part 1 and Part 2 - Approximately 4 years ]
  • Disease control rate (DCR) by RECIST v 1.1 and by irRECIST [ Time Frame: Part 1 and Part 2 - Approximately 4 years ]
  • Progression-free survival (PFS) by RECIST v 1.1 and by irRECIST [ Time Frame: Part 1 and Part 2 - Approximately 4 years ]
  • Overall survival (OS) [ Time Frame: Part 1 and Part 2 - Approximately 4 years ]
  • PK Parameter: AUC, 0-last assessment [ Time Frame: Part 1 and Part 2 - Approximately 4 years ]
  • PK Parameter: AUC, 0 to infinity [ Time Frame: Part 1 and Part 2 - Approximately 4 years ]
  • PK Parameter: AUC at steady state [ Time Frame: Part 1 and Part 2 - Approximately 4 years ]
  • PK Parameter: Minimum Concentration (Cmin) [ Time Frame: Part 1 and Part 2 - Approximately 4 years ]
  • PK Parameter: Maximum Concentration (Cmax) [ Time Frame: Part 1 and Part 2 - Approximately 4 years ]
  • PK Parameter: Clearance (CL) [ Time Frame: Part 1 and Part 2 - Approximately 4 years ]
  • PK Parameter: Cmin at steady state (Cmin,ss) [ Time Frame: Part 1 and Part 2 - Approximately 4 years ]
  • PK Parameter: Cmax at steady state (Cmax, ss) [ Time Frame: Part 1 and Part 2 - Approximately 4 years ]
  • PK Parameter: Volume of Distribution (Vz) [ Time Frame: Part 1 and Part 2 - Approximately 4 years ]
  • PK Parameter: terminal half-life (t1/2) [ Time Frame: Part 1 and Part 2 - Approximately 4 years ]
  • Pharmacodynamic profile as assessed by receptor occupancy [ Time Frame: Part 1 and 2 - Approximately 4 years ]
  • Immunogenicity as assessed by the presence of anti-drug antibodies [ Time Frame: Part 1 and 2 -Approximately 4 years ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Phase 1 Study of TSR-022, an Anti-TIM-3 Monoclonal Antibody, in Patients With Advanced Solid Tumors (AMBER)
Official Title  ICMJE 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)
Brief Summary 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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Advanced or Metastatic Solid Tumors
Intervention  ICMJE
  • Drug: TSR-022
    TSR-022 is a humanized monoclonal IgG4 antibody binds to TIM3
    Other Name: TIM 3
  • Drug: TSR-042, an anti-PD-1 antibody
    TSR-042 is a humanized monoclonal IgG4 antibody binds to PD-1
    Other Name: PD-1
  • Drug: TSR-033, an anti-LAG-3 antibody
    TSR-033 is a humanized monoclonal IgG4 antibody binds to Lag 3
    Other Name: Lag3
Study Arms  ICMJE
  • Experimental: Part 1- Dose Escalation

    1a: 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

    Interventions:
    • Drug: TSR-022
    • Drug: TSR-042, an anti-PD-1 antibody
    • Drug: TSR-033, an anti-LAG-3 antibody
  • Experimental: Part 2- Expansion Cohorts

    Part 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

    Interventions:
    • Drug: TSR-022
    • Drug: TSR-042, an anti-PD-1 antibody
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 30, 2019)
873
Original Estimated Enrollment  ICMJE
 (submitted: June 24, 2016)
402
Estimated Study Completion Date  ICMJE June 2022
Estimated Primary Completion Date June 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Beth Zaharoff (781) 209-5485 bzaharoff@tesarobio.com
Listed Location Countries  ICMJE Spain,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02817633
Other Study ID Numbers  ICMJE 4020-01-001
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Tesaro, Inc.
Study Sponsor  ICMJE Tesaro, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Ying Wang, PhD, MD, Tesaro, Inc.
PRS Account Tesaro, Inc.
Verification Date March 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP