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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 : March 19, 2019
Sponsor:
Information provided by (Responsible Party):
Tesaro, Inc.

Study Description
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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.

Condition or disease Intervention/treatment Phase
Advanced or Metastatic Solid Tumors Drug: TSR-022 Drug: TSR-042, an anti-PD-1 antibody Drug: TSR-033, an anti-LAG-3 antibody Phase 1

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 819 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Study Start Date : July 2016
Estimated Primary Completion Date : December 2019
Estimated Study Completion Date : June 2020

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Arms and Interventions
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Arm Intervention/treatment
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-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
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)

 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


Outcome Measures
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Primary Outcome Measures :
  1. 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 ]
  2. 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 ]
  3. Recommended Phase 2 dose (RP2D) and schedule as monotherapy and in combination therapy [ Time Frame: Part 1 and Part 2 - Approximately 4 years ]

Secondary Outcome Measures :
  1. Safety and tolerability of TSR-022 using CTCAE v.4.03 [ Time Frame: Part 2 - Approximately 2 years ]
  2. Overall Response Rate (ORR) by RECIST v. 1.1 (Part 1) [ Time Frame: Part 1 and Part 2 - Approximately 4 years ]
  3. ORR by immune-related RECIST (irRECIST) [ Time Frame: Part 1 and Part 2 - Approximately 4 years ]
  4. Duration of response (DOR) by RECIST v 1.1 [ Time Frame: Part 1 and Part 2 - Approximately 4 years ]
  5. Disease control rate (DCR) by RECIST v 1.1 and by irRECIST [ Time Frame: Part 1 and Part 2 - Approximately 4 years ]
  6. Progression-free survival (PFS) by RECIST v 1.1 and by irRECIST [ Time Frame: Part 1 and Part 2 - Approximately 4 years ]
  7. Overall survival (OS) [ Time Frame: Part 1 and Part 2 - Approximately 4 years ]
  8. Immunogenicity as assessed by the presence of anti-drug antibodies [ Time Frame: Part 1 and 2 -Approximately 4 years ]
  9. Maximum plasma concentration (Cmax) of TSR-022 [ Time Frame: Part 1 - Approximately 9 months ]
  10. Minimum plasma concentration (Cmin) of TSR-022 [ Time Frame: Part 1 - Approximately 9 months ]
  11. Area under the curve (AUC),0-infinity of TSR-022 [ Time Frame: Part 1 - Approximately 9 months ]
  12. Area under the curve at steady state (AUC,ss) of TSR-022 [ Time Frame: Part 1 - Approximately 9 months ]
  13. Maximum plasma concentration at steady state (Cmax,ss) of TSR-022 [ Time Frame: Part 1 - Approximately 9 months ]
  14. Minimum plasma concentration at steady state (Cmin,ss) of TSR-022 [ Time Frame: Part 1 - Approximately 9 months ]
  15. Maximum plasma concentration (Cmax) of TSR-042 [ Time Frame: Part 1 - Approximately 9 months ]
  16. Minimum plasma concentration (Cmin) of TSR-042 [ Time Frame: Part 1 - Approximately 9 months ]
  17. Area under the curve (AUC),0-infinity of TSR-042 [ Time Frame: Part 1 - Approximately 9 months ]
  18. Area under the curve at steady state (AUC,ss) of TSR-042 [ Time Frame: Part 1 - Approximately 9 months ]
  19. Maximum plasma concentration at steady state (Cmax,ss) of TSR-042 [ Time Frame: Part 1 - Approximately 9 months ]
  20. Minimum plasma concentration at steady state (Cmin,ss) of TSR-042 [ Time Frame: Part 1 - Approximately 9 months ]
  21. Maximum plasma concentration (Cmax) of TSR-033 [ Time Frame: Part 1 - Approximately 9 months ]
  22. Minimum plasma concentration (Cmin) of TSR-033 [ Time Frame: Part 1 - Approximately 9 months ]
  23. Area under the curve (AUC),0-infinity of TSR-033 [ Time Frame: Part 1 - Approximately 9 months ]
  24. Area under the curve at steady state (AUC,ss) of TSR-033 [ Time Frame: Part 1 - Approximately 9 months ]
  25. Maximum plasma concentration at steady state (Cmax,ss) of TSR-033 [ Time Frame: Part 1 - Approximately 9 months ]
  26. Minimum plasma concentration at steady state (Cmin,ss) of TSR-033 [ Time Frame: Part 1 - Approximately 9 months ]
  27. Maximum plasma concentration (Cmax) of nivolumab [ Time Frame: Part 1 - Approximately 9 months ]
  28. Minimum plasma concentration (Cmin) of nivolumab [ Time Frame: Part 1 - Approximately 9 months ]
  29. Area under the curve (AUC),0-infinity of nivolumab [ Time Frame: Part 1 - Approximately 9 months ]
  30. Area under the curve at steady state (AUC,ss) of nivolumab [ Time Frame: Part 1 - Approximately 9 months ]
  31. Maximum plasma concentration at steady state (Cmax,ss) of nivolumab [ Time Frame: Part 1 - Approximately 9 months ]
  32. Minimum plasma concentration at steady state (Cmin,ss) of nivolumab [ Time Frame: Part 1 - Approximately 9 months ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 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
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02817633


Contacts
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Contact: Beth Zaharoff (781) 209-5485 bzaharoff@tesarobio.com

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Sponsors and Collaborators
Tesaro, Inc.
Investigators
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Study Director: Ying Wang, PhD, MD, Tesaro, Inc.
More Information
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Responsible Party: Tesaro, Inc.
ClinicalTrials.gov Identifier: NCT02817633     History of Changes
Other Study ID Numbers: 4020-01-001
First Posted: June 29, 2016    Key Record Dates
Last Update Posted: March 19, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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:
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Neoplasms
Antibodies
Immunoglobulins
 Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs