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A Phase 1 Dose Escalation and Cohort Expansion Study of TSR-042, an Anti-PD-1 Monoclonal Antibody, in Patients With Advanced Solid Tumors

This study is currently recruiting participants.
See Contacts and Locations
Verified August 2016 by Tesaro, Inc.
Information provided by (Responsible Party):
Tesaro, Inc. Identifier:
First received: March 9, 2016
Last updated: August 10, 2016
Last verified: August 2016
This is a multicenter, open-label, first-in-human Phase 1 study evaluating the anti programmed death receptor 1 (anti-PD-1) antibody TSR-042 in patients with advanced solid tumors who have limited available treatment options. The study will be conducted in 2 parts: dose escalation and cohort expansion.

Condition Intervention Phase
Advanced or Metastatic Solid Tumors Biological: TSR-042 Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1 Dose Escalation and Cohort Expansion Study of TSR-042, an Anti-PD-1 Monoclonal Antibody, in Patients With Advanced Solid Tumors

Further study details as provided by Tesaro, Inc.:

Primary Outcome Measures:
  • Safety and tolerability of TSR-042 using Common Terminology Criteria for Adverse Events (CTCAE v4.03) in patients with advanced solid tumors [ Time Frame: Part 1 Dose Escalation - Approximately 9 months ]
  • Antitumor activity of TSR-042 in patients with advanced solid tumors, in terms of objective response rate (ORR) as assessed by the Investigators using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 [ Time Frame: Part 2 Expansion - Approximately 12 months ]
  • Recommended Phase 2 dose (RP2D) and schedule [ Time Frame: Part 1 and Part 2 - Approximately 12 months ]

Secondary Outcome Measures:
  • PD-1 receptor occupancy prior to and after the first dose of TSR-042 to measure changes in serum cytokines [ Time Frame: Part 1 - Approximately 12 months ]
  • Overall Response Rate (ORR) as assessed by using RECIST v1.1 [ Time Frame: Part 1 - Approximately 12 months ]
  • Safety and tolerability of TSR-042 using CTCAE v4.03 [ Time Frame: Part 2 - Approximately 12 months ]
  • Immunogenicity of TSR-042 [ Time Frame: Part 1 and Part 2 - Approximately 12 months ]
  • ORR by immune-related RECIST (irRECIST) [ Time Frame: Part 1 and Part 2 - Approximately 24 months ]
  • Duration of Response (DOR) by RECIST v 1.1 [ Time Frame: Part 1 and Part 2 - Approximately 24 months ]
  • Disease Control Rate (DCR) by RECIST v 1.1 and by irRECIST [ Time Frame: Part 1 and Part 2 - Approximately 24 months ]
  • Progression-free survival (PFS) by RECIST v 1.1 and by irRECIST [ Time Frame: Part 1 and Part 2 - Approximately 24 months ]
  • Overall Survival (OS) [ Time Frame: Part 1 and Part 2 - Approximately 24 months ]
  • Pharmacokinetic (PK) Parameter: Area Under the Concentration (AUC),0-last [ Time Frame: Approximately 12 months ]
  • PK Parameter: AUC,0-infinity [ Time Frame: Approximately 12 months ]
  • PK Parameter: AUC at steady state (AUC,ss) [ Time Frame: Approximately 12 months ]
  • PK Parameter: Minimum Concentration (Cmin) [ Time Frame: Approximately 12 months ]
  • PK Parameter: Maximum Concentration (Cmax) [ Time Frame: Approximately 12 months ]
  • PK Parameter: Cmin,ss [ Time Frame: Approximately 12 months ]
  • PK Parameter: Cmax,ss [ Time Frame: Approximately 12 months ]
  • PK Parameter: Clearance (CL) [ Time Frame: Approximately 12 months ]
  • PK Parameter: Volume of Distribution (Vz) [ Time Frame: Approximately 12 months ]

Estimated Enrollment: 379
Study Start Date: March 2016
Estimated Study Completion Date: December 2019
Estimated Primary Completion Date: February 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Part 1 - Dose Escalation

Using a modified 3+3 design, Part 1 (dose escalation) will initially evaluate ascending weight-based dose levels of TSR-042 administered via intravenous (IV) infusion, once every two weeks.

Part 2 - Expansion Cohort - Part 2 of the study will further explore the safety and clinical activity of TSR-042 in patients with selected tumor types. Dosing in Part 2 will be initiated with the dose determined to be safe based on dose limiting toxicities (DLTs) in Part 1 with consideration of available Pharmacokinetic/Pharmacodynamic (PK/PD) data.

Biological: TSR-042
TSR-042 is a humanized monoclonal antibody that binds with high affinity to PD-1 resulting in inhibition of binding to programmed death receptor ligands 1 and 2 (PD-L1 and PD-L2).


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Patient with histologically or cytologically proven advanced (unresectable) or metastatic solid tumor and has disease progression after treatment with available therapies that are known to confer clinical benefit or who are intolerant to treatment that meets the following requirements for the part of the study they will participate in:

    1. Part 1: Any advanced or metastatic solid tumor patient
    2. Part 2: For selected tumor types archival tumor tissue available that is formalin-fixed and paraffin-embedded or a new biopsy must be performed to obtain a tissue sample prior to study treatment initiation.
  • Female patients, if of childbearing potential, must have a negative serum pregnancy test within 72 hours prior to the date of the first dose of study medication.
  • Female patients of childbearing potential and male patients must agree to use 2 adequate methods of contraception with their partner starting with the screening visit through 150 days after the last dose of study therapy.
  • Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2 for Part 1 and ≤ 1 for Part 2.
  • Adequate organ function.

Exclusion Criteria:

  • Patient has received prior therapy with an anti-programmed death receptor 1 (anti-PD-1), anti-PD-1-ligand-1 (anti-PD-L1), or anti-PD-1 ligand-2 (anti-PD-L2) agent.
  • Known uncontrolled central nervous system (CNS) metastases and/or carcinomatous meningitis. Note: Patients with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least 4 weeks prior to the first dose of study treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are clinically stable off steroids for at least 7 days prior to study treatment. Carcinomatous meningitis precludes a patient from study participation regardless of clinical stability.
  • Known additional malignancy that progressed or required active treatment within the last 2 years. Exceptions include basal cell carcinoma of the skin, squamous cell cancer (SqCC) of the skin that has undergone potentially curative therapy, or in situ cervical cancer.
  • Poor medical risk.
  • Pregnant or breastfeeding, or expecting to conceive children within the projected duration of the study.
  • 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.
  • Known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies).
  • 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).
  • Active autoimmune disease that has required systemic treatment in the past 2 years (ie, with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
  • History of interstitial lung disease.
  • Patient has not recovered (ie, to ≤ Grade 1 or to baseline) from radiation- and chemotherapy-induced adverse events (AEs) or received transfusion of blood products (including platelets or red blood cells) or 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.
  • Currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks prior to the first dose of study drug.
  • 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. Note: palliative radiation therapy to a small field ≥ 1 week prior to Day 1 of study treatment may be allowed.
  • Patient has not recovered adequately (≤ Grade 1) from AEs and/or complications from any major surgery prior to starting therapy.
  • Patient has received a vaccine within 7 days of planned start of study therapy.
  • Known hypersensitivity to TSR-042 components or excipients.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT02715284

Contact: Clinical Trial Management Group

United States, Arizona
Goodyear, Arizona, United States, 85338
Contact: Lisa Blaydorn, RN    623-207-3183   
Scottsdale, Arizona, United States, 85258
Contact: Joyce Schaffer    480-323-1339   
United States, Texas
San Antonio, Texas, United States, 78229
Contact: Isabel Jimenez, RN, MSN    210-593-5252   
Sponsors and Collaborators
Tesaro, Inc.
Study Director: Ellie Im, MD Tesaro, Inc.
  More Information

Responsible Party: Tesaro, Inc. Identifier: NCT02715284     History of Changes
Other Study ID Numbers: 4010-01-001
Study First Received: March 9, 2016
Last Updated: August 10, 2016
Individual Participant Data  
Plan to Share IPD: No

Keywords provided by Tesaro, Inc.:
Metastatic solid tumors
Advanced solid tumors

Additional relevant MeSH terms:
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs processed this record on June 26, 2017