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A Study of TSR-022 in Participants With Advanced Solid Tumors (AMBER)

Trial Status: Active

This is a multicenter, open-label, first-in-human Phase 1 study evaluating the anti-T cell immunoglobulin and mucin containing protein-3 (TIM-3) antibody TSR-022. The study will be conducted in 2 parts: with Part 1 consisting of dose escalation and Part 2 dose expansion. Part 1 will determine the recommended Phase 2 dose (RP2D) of TSR-022 as a single agent (Part 1a); in combination with anti-programmed cell death protein-1 (PD-1) antibody, nivolumab (Part 1b); in combination with anti-PD-1 antibody, TSR-042 (Part 1c); in combination with TSR-042 and anti-lymphocyte-activation gene 3 (LAG-3) antibody, TSR-033 (Part 1d); in combination with TSR-042 in participants not previously treated with programmed death-ligand 1 [PD-(L)1] (Part 1e) and in combination with docetaxel (Part 1f). Part 2 of the study will evaluate the antitumor activity of TSR-022, both as monotherapy and in combination with TSR-042 in participants with pre-specified tumor types.

Inclusion Criteria

  • Participant is at least 18 years of age.
  • Female participants of childbearing potential must have a negative serum or urine pregnancy test within 72 hours prior to the date of the first dose of study medication or be of non-childbearing potential.
  • Participant has adequate organ function. Inclusion Criteria for Participants in Part 1 and Part 2 Cohorts A, B, and C:
  • Participant with advanced or metastatic solid tumor who meets the requirements for the part of the study/cohort he/she will participate in, as follows:
  • Part 1: Participant with advanced or metastatic solid tumor and has disease progression after treatment with available therapies that are known to confer clinical benefit or who is intolerant to treatment (except for Part 1e, where special interest tumor types will be specified by the Sponsor).
  • Part 1e:
  • Advanced or metastatic melanoma participants who have not been previously treated with anti-PD-1, anti-PD-L1, or anti cytotoxic T lymphocyte-associated protein-(CTLA-4) therapies. Participant may be treatment naïve.
  • Advanced or metastatic NSCLC participants who have not received anti-PD-1 or anti-PD-L1 therapies and have received <=2 prior lines of treatment.
  • Part 2: Histologically proven advanced (unresectable) or metastatic solid tumor that is measurable by computed tomography (CT) or magnetic resonance imaging (MRI) per RECIST version 1.1 criteria and meets 1 of the following disease types:
  • Cohort A (melanoma) - Participants with advanced or metastatic melanoma who have progressed following treatment with an anti-PD-1 or anti-PD-L1 antibody.
  • Cohort B (NSCLC) - Participants with advanced or metastatic NSCLC who have progressed following:
  • Treatment with an anti-PD-1 or anti-PD-L1 antibody.
  • Cohort C (CRC) - Participants with advanced/metastatic CRC who have progressed following standard treatment which must include fluoropyrimidine, oxaliplatin, and irinotecan, unless contraindicated. Participants should have received no more than 3 prior lines of therapy (including adjuvant therapy).
  • Biopsies
  • Part 1: Participants must have archival tumor tissue available that is formalin-fixed and paraffin-embedded. Tumor tissue must be requested from off-site locations and confirmed available prior to dosing.
  • For participants in Part 1 who do not have archival tissue, a new biopsy must be performed to obtain tumor tissue.
  • Part 2 Cohorts A, B, and C: All participants enrolled in Part 2 Cohorts A to C are required to have fresh tumor tissue biopsy prior to dosing. Archival tissue should also be provided (if available) to enable a longitudinal analysis of tumor biomarkers.
  • If a participants has had a biopsy prior to entering the 21-day screening period and within approximately 12 weeks of study treatment, that biopsy may be accepted as the Baseline fresh biopsy.
  • All participants are also required to have lesions amenable to biopsy and to agree to tumor biopsies prior to the initiation of treatment (as noted above) approximately 4 to 6 weeks after initiating treatment, and, if possible, upon treatment discontinuation (for participant with PD).
  • Inclusion Criteria for Participants in Part 2 Cohort D
  • Participants with advanced or metastatic NSCLC that is measurable by CT or MRI per RECIST version 1.1 criteria and meet the following criteria:
  • NSCLC histology includes squamous or non-squamous cell carcinoma.
  • Participants have received no more than 2 prior lines of therapy, which must include a platinum-based chemotherapy (eg, cisplatin, carboplatin) and an anti-PD-(L)1 antibody.
  • Participants must have documented radiographic progression by RECIST version 1.1 criteria on prior anti-PD-1 or anti-PD-L1 therapy.
  • Biopsies
  • If a participant has had a biopsy prior to entering the 35-day screening period and within approximately 12 weeks of study treatment, that biopsy may be accepted as the Baseline fresh biopsy.

Exclusion Criteria

  • History of Grade >=3 immune-related AE with prior immunotherapy, with the exception of non-clinically significant lab abnormalities.
  • Participant has known uncontrolled central nervous system (CNS) metastases and/or carcinomatous meningitis.
  • Participant has a known additional malignancy that progressed or required active treatment within the last 2 years. Participants with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen may be included only after discussion with the Medical Monitor.
  • Participant is considered a poor medical risk due to a serious, uncontrolled medical disorder, nonmalignant systemic disease or active infection requiring systemic therapy.
  • Participant is pregnant or breastfeeding, or expecting to conceive children within the projected duration of the study, starting with the Screening Visit through 150 days after the last dose of study treatment.
  • Participant has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment.
  • Participant has a known history of human immunodeficiency virus (HIV) infection or HIV 1/2 antibodies.
  • Participant has known active hepatitis B (eg, hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (eg, hepatitis C virus ribonucleic acid [HCV RNA] [qualitative] is detected).
  • Participant has an active autoimmune disease that has required systemic treatment (ie, with use of disease-modifying agents, corticosteroids or immunosuppressive drugs).
  • Participant has a history of pneumonitis.
  • Participant has not recovered (ie, to Grade <=1 or to Baseline) from radiation- and chemotherapy-induced AEs, has received transfusion of blood products (including platelets or red blood cells), or has received administration of colony-stimulating factors (including granulocyte-colony stimulating factor [G-CSF], granulocyte macrophage colony-stimulating factor [GM-CSF], or recombinant erythropoietin) within 3 weeks prior to the first dose of study drug.
  • Participant is currently participating and receiving study therapy or has participated in a study of an investigational agent and received investigational therapy or used an investigational device within 4 weeks prior to the first dose of study drug.
  • Participant has received prior anticancer therapy (chemotherapy, targeted therapies, radiotherapy, or immunotherapy) within 21 days, or less than 5 times the half-life of the most recent therapy prior to study Day 1, whichever is shorter.
  • Participant has not recovered adequately (Grade <=1) from AEs and/or complications from any major surgery prior to starting therapy.
  • Participant has received a vaccine within 7 days of planned start of study therapy.
  • Participant has a known hypersensitivity to TSR-022 components or excipients, or, if applicable, nivolumab, TSR-042, or TSR-033 components or excipients. Exclusion Criteria for Participants in Part 1 and Part 2 Cohorts A, B, and C
  • Participant received prior therapy as defined below:
  • Part 1a: Anti-CTLA-4, anti-PD-1, anti-PD-1-ligand-1 (anti-PD-L1), or anti-PD-1 ligand-2 (anti-PD-L2) agent within 3 weeks (that is, 21 days) prior to initiation of study treatment.
  • Part 1b, Part 1c, Part 1d, and Part1f: Anti-CTLA-4 within 3 weeks (that is, 21 days) prior to initiation of study treatment and/or prior treatment with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-TIM-3, or anti-LAG-3, or docetaxel agent that resulted in permanent discontinuation due to an AE.
  • Part 1e: Prior treatment with with an anti-PD-(L)1, anti-LAG-3 or anti-TIM-3.
  • NSCLC participants with known EGFR mutations, ALK translocations, or ROS1 mutations.
  • Participants with uveal melanoma.
  • Part 1f: History of severe hypersensitivity reaction to docetaxel, paclitaxel, or other drugs formulated with polysorbate 80.
  • Part 2 Cohorts A, B, and C combination arms (TSR-022 + TSR-042):
  • Prior treatment with anti-PD-1, anti-PD-L1, or anti-PD-L2 agent that resulted in permanent discontinuation due to an AE.
  • Prior treatment with an anti-LAG-3 or anti-TIM-3. Exclusion Criteria for Participants in Part 2 Cohort D
  • A participant with negative (as determined by Central Testing Lab) or unevaluable TIM-3 expression from tissue obtained prior to study entry will not be eligible for the study.
  • Participant has received prior therapy as defined below:
  • Prior treatment with anti-PD-1, anti-PD-L1, or anti-PD-L2 agent that resulted in permanent discontinuation due to an AE.
  • Prior treatment with an anti-LAG-3 or anti-TIM-3.
  • Radiologic or clinical progression <= 8 weeks after initiation of prior anti-PD-1 or anti-PD-L1 antibody.
  • Participants with known EGFR mutation, ALK translocation, or ROS1 mutation.

Arizona

Scottsdale
Mayo Clinic in Arizona
Status: CLOSED_TO_ACCRUAL

California

Los Angeles
UCLA / Jonsson Comprehensive Cancer Center
Status: ACTIVE

Colorado

Aurora
University of Colorado Hospital
Status: CLOSED_TO_ACCRUAL

Connecticut

New Haven
Yale University
Status: ACTIVE

District of Columbia

Washington
MedStar Georgetown University Hospital
Status: ACTIVE

Florida

Jacksonville
Mayo Clinic in Florida
Status: CLOSED_TO_ACCRUAL
Tampa
Moffitt Cancer Center
Status: ACTIVE

Georgia

Atlanta
Emory University Hospital / Winship Cancer Institute
Status: ACTIVE

Illinois

Chicago
University of Chicago Comprehensive Cancer Center
Status: TEMPORARILY_CLOSED_TO_ACCRUAL

Iowa

Iowa City
University of Iowa / Holden Comprehensive Cancer Center
Status: ACTIVE

Massachusetts

Boston
Beth Israel Deaconess Medical Center
Status: APPROVED
Massachusetts General Hospital Cancer Center
Status: ACTIVE

Minnesota

Rochester
Mayo Clinic in Rochester
Status: CLOSED_TO_ACCRUAL

Missouri

Saint Louis
Siteman Cancer Center at Washington University
Status: WITHDRAWN

New Jersey

Hackensack
Hackensack University Medical Center
Status: ACTIVE

New York

Bronx
Montefiore Medical Center-Einstein Campus
Status: ACTIVE
New York
Laura and Isaac Perlmutter Cancer Center at NYU Langone
Status: CLOSED_TO_ACCRUAL

Ohio

Cleveland
Case Comprehensive Cancer Center
Status: ACTIVE

Oklahoma

Oklahoma City
University of Oklahoma Health Sciences Center
Status: ACTIVE

Pennsylvania

Pittsburgh
University of Pittsburgh Cancer Institute (UPCI)
Status: ACTIVE

South Carolina

Charleston
Medical University of South Carolina
Status: CLOSED_TO_ACCRUAL

Texas

Houston
M D Anderson Cancer Center
Status: ACTIVE
San Antonio
Cancer Therapy and Research Center at The UT Health Science Center at San Antonio
Status: WITHDRAWN

Wisconsin

Madison
University of Wisconsin Hospital and Clinics
Status: CLOSED_TO_ACCRUAL

Trial Phase Phase I

Trial Type Treatment

Lead Organization
Tesaro Inc

  • Primary ID 213348
  • Secondary IDs NCI-2016-01254, 4020-01-001
  • Clinicaltrials.gov ID NCT02817633