Clinical Trial - NCT02817633

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

Recruiting

Sponsor: Tesaro, Inc.

Collaborators:

Information provided by (Responsible party): Sponsor

ClinicalTrials.gov Identifier: NCT02817633

Protocol Info

Short Description: Phase 1 of TSR-022 in Advanced Solid Tumors
Long Description: A Phase 1 Dose Escalation and Cohort Expansion Study of TSR-022, an Anti-TIM-3 Monoclonal Antibody, in Patients With Advanced Solid Tumors
MGH Status: Open
Sponsor: Tesaro
Disease Program: Phase I

Next Steps


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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.
Condition Title Intervention Phase
Advanced or Metastatic Solid Tumors TSR-022 TSR-042, an anti-PD-1 antibody TSR-033, an anti-LAG-3 antibody Phase 1
Study Type Interventional
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)

Primary Outcome Measures

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] [Designated as safety issue: ]

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] [Designated as safety issue: ]

Recommended Phase 2 dose (RP2D) and schedule as monotherapy and in combination therapy [Time Frame: Part 1 and Part 2 - Approximately 4 years] [Designated as safety issue: ]


Secondary Outcome Measures

Safety and tolerability of TSR-022 using CTCAE v.4.03 [Time Frame: Part 2 - Approximately 2 years] [Designated as safety issue: ]

Overall Response Rate (ORR) by RECIST v. 1.1 (Part 1) [Time Frame: Part 1 and Part 2 - Approximately 4 years] [Designated as safety issue: ]

ORR by immune-related RECIST (irRECIST) [Time Frame: Part 1 and Part 2 - Approximately 4 years] [Designated as safety issue: ]

Duration of response (DOR) by RECIST v 1.1 [Time Frame: Part 1 and Part 2 - Approximately 4 years] [Designated as safety issue: ]

Disease control rate (DCR) by RECIST v 1.1 and by irRECIST [Time Frame: Part 1 and Part 2 - Approximately 4 years] [Designated as safety issue: ]

Progression-free survival (PFS) by RECIST v 1.1 and by irRECIST [Time Frame: Part 1 and Part 2 - Approximately 4 years] [Designated as safety issue: ]

Overall survival (OS) [Time Frame: Part 1 and Part 2 - Approximately 4 years] [Designated as safety issue: ]

Immunogenicity as assessed by the presence of anti-drug antibodies [Time Frame: Part 1 and 2 -Approximately 4 years] [Designated as safety issue: ]

Maximum plasma concentration (Cmax) of TSR-022 [Time Frame: Part 1 - Approximately 9 months] [Designated as safety issue: ]

Minimum plasma concentration (Cmin) of TSR-022 [Time Frame: Part 1 - Approximately 9 months] [Designated as safety issue: ]

Area under the curve (AUC),0-infinity of TSR-022 [Time Frame: Part 1 - Approximately 9 months] [Designated as safety issue: ]

Area under the curve at steady state (AUC,ss) of TSR-022 [Time Frame: Part 1 - Approximately 9 months] [Designated as safety issue: ]

Maximum plasma concentration at steady state (Cmax,ss) of TSR-022 [Time Frame: Part 1 - Approximately 9 months] [Designated as safety issue: ]

Minimum plasma concentration at steady state (Cmin,ss) of TSR-022 [Time Frame: Part 1 - Approximately 9 months] [Designated as safety issue: ]

Maximum plasma concentration (Cmax) of TSR-042 [Time Frame: Part 1 - Approximately 9 months] [Designated as safety issue: ]

Minimum plasma concentration (Cmin) of TSR-042 [Time Frame: Part 1 - Approximately 9 months] [Designated as safety issue: ]

Area under the curve (AUC),0-infinity of TSR-042 [Time Frame: Part 1 - Approximately 9 months] [Designated as safety issue: ]

Area under the curve at steady state (AUC,ss) of TSR-042 [Time Frame: Part 1 - Approximately 9 months] [Designated as safety issue: ]

Maximum plasma concentration at steady state (Cmax,ss) of TSR-042 [Time Frame: Part 1 - Approximately 9 months] [Designated as safety issue: ]

Minimum plasma concentration at steady state (Cmin,ss) of TSR-042 [Time Frame: Part 1 - Approximately 9 months] [Designated as safety issue: ]

Maximum plasma concentration (Cmax) of TSR-033 [Time Frame: Part 1 - Approximately 9 months] [Designated as safety issue: ]

Minimum plasma concentration (Cmin) of TSR-033 [Time Frame: Part 1 - Approximately 9 months] [Designated as safety issue: ]

Area under the curve (AUC),0-infinity of TSR-033 [Time Frame: Part 1 - Approximately 9 months] [Designated as safety issue: ]

Area under the curve at steady state (AUC,ss) of TSR-033 [Time Frame: Part 1 - Approximately 9 months] [Designated as safety issue: ]

Maximum plasma concentration at steady state (Cmax,ss) of TSR-033 [Time Frame: Part 1 - Approximately 9 months] [Designated as safety issue: ]

Minimum plasma concentration at steady state (Cmin,ss) of TSR-033 [Time Frame: Part 1 - Approximately 9 months] [Designated as safety issue: ]

Maximum plasma concentration (Cmax) of nivolumab [Time Frame: Part 1 - Approximately 9 months] [Designated as safety issue: ]

Minimum plasma concentration (Cmin) of nivolumab [Time Frame: Part 1 - Approximately 9 months] [Designated as safety issue: ]

Area under the curve (AUC),0-infinity of nivolumab [Time Frame: Part 1 - Approximately 9 months] [Designated as safety issue: ]

Area under the curve at steady state (AUC,ss) of nivolumab [Time Frame: Part 1 - Approximately 9 months] [Designated as safety issue: ]

Maximum plasma concentration at steady state (Cmax,ss) of nivolumab [Time Frame: Part 1 - Approximately 9 months] [Designated as safety issue: ]

Minimum plasma concentration at steady state (Cmin,ss) of nivolumab [Time Frame: Part 1 - Approximately 9 months] [Designated as safety issue: ]

Estimated Enrollment: 819
Study Start Date: July 2016
Estimated Study Completion Date: June 2020
Estimated Primary Completion Date: December 2019
Arms Assigned Interventions

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
Drug:TSR-033, an anti-LAG-3 antibody
TSR-033 is a humanized monoclonal IgG4 antibody binds to Lag 3

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, Cohort C: (CRC) no more than 3 lines of prior therapy (currently closed to enrollment)

Eligibility

Ages Eligible for Study: N/A-N/A

Genders Eligible for Study: All

Accepts Healthly Volunteers: No

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 two methods 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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT02817633

Locations

  • United States, Arizona
    • Goodyear, Arizona, United States, 85338
    • Phoenix, Arizona, United States, 85054
    • Scottsdale, Arizona, United States, 85258
    • Tucson, Arizona, United States, 85711
  • United States, California
    • Encinitas, California, United States, 92024
    • Fresno, California, United States, 93720
    • Los Angeles, California, United States, 90095
    • San Marcos, California, United States, 92069
    • Whittier, California, United States, 90603
  • United States, Colorado
    • Aurora, Colorado, United States, 80045
    • Denver, Colorado, United States, 80218
  • United States, Connecticut
    • New Haven, Connecticut, United States, 06520
  • United States, District of Columbia
    • Washington, District of Columbia, United States, 20007
  • United States, Florida
    • Jacksonville, Florida, United States, 32224
    • Miami Beach, Florida, United States, 33140
    • Sarasota, Florida, United States, 34232
    • Tampa, Florida, United States, 33612
  • United States, Georgia
    • Atlanta, Georgia, United States, 30322
  • United States, Illinois
    • Arlington Heights, Illinois, United States, 60005
    • Chicago, Illinois, United States, 60637
  • United States, Iowa
    • Iowa City, Iowa, United States, 52242
  • United States, Kansas
    • Wichita, Kansas, United States, 67214
  • United States, Maryland
    • Rockville, Maryland, United States, 20850
  • United States, Massachusetts
    • Boston, Massachusetts, United States, 02114
  • United States, Michigan
    • Detroit, Michigan, United States, 48202
  • United States, Minnesota
    • Rochester, Minnesota, United States, 55905
  • United States, New Jersey
    • Hackensack, New Jersey, United States, 07671
  • United States, New Mexico
    • Farmington, New Mexico, United States, 87401
  • United States, New York
    • Bronx, New York, United States, 10461
    • New York, New York, United States, 10016
  • United States, Ohio
    • Cincinnati, Ohio, United States, 45242
    • Cleveland, Ohio, United States, 44106
  • United States, Oregon
    • Eugene, Oregon, United States, 97401
  • United States, Pennsylvania
    • Allentown, Pennsylvania, United States, 18045
    • Bethlehem, Pennsylvania, United States, 18015
    • Pittsburgh, Pennsylvania, United States, 15232
  • United States, South Carolina
    • Charleston, South Carolina, United States, 29425
    • Greenville, South Carolina, United States, 29605
  • United States, Tennessee
    • Nashville, Tennessee, United States, 37203
  • United States, Texas
    • Austin, Texas, United States, 78705
    • Dallas, Texas, United States, 75246
    • Fort Worth, Texas, United States, 76104
    • Houston, Texas, United States, 77030
    • McAllen, Texas, United States, 78503
    • Paris, Texas, United States, 75460
    • San Antonio, Texas, United States, 78229
    • Temple, Texas, United States, 76508
    • Tyler, Texas, United States, 75702
  • United States, Virginia
    • Fairfax, Virginia, United States, 22031
  • United States, Washington
    • Kennewick, Washington, United States, 99336
    • Vancouver, Washington, United States, 98684
  • United States, Wisconsin
    • Madison, Wisconsin, United States, 53792
  • Spain,
    • Madrid, , Spain, 28027
    • Madrid, , Spain, 28040
    • Madrid, , Spain, 28050
    • Málaga, , Spain, 29010
    • Pamplona, , Spain, 31008

Sponsors and Collaborators

Tesaro, Inc.

More Information

No publications provided

Responsible Party: Sponsor
ClinicalTrials.gov Identifier: NCT02817633
Other Study ID Numbers:
Study First Received:
Last Updated:
Health Authority:

Keywords provided by Tesaro, Inc.:

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

Additional relevant MeSH terms:

Neoplasms

Antibodies

Immunoglobulins

Antibodies, Monoclonal

Next Steps


If you are interested in this protocol or in other treatment options at Massachusetts General Hospital, please Request a Consultation.







ClinicalTrials.gov processed this data on May 16, 2019