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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 (GARNET)

This study is currently recruiting participants.
Verified November 2017 by Tesaro, Inc.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02715284
First Posted: March 22, 2016
Last Update Posted: November 17, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
Tesaro, Inc.
  Purpose
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. The cohort expansion may include various tumor types, including endometrial, Non-Small Cell Lung cancer, and MSI-H solid tumors.

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

Study Type: Interventional
Study Design: 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-042, an Anti-PD-1 Monoclonal Antibody, in Patients With Advanced Solid Tumors

Further study details as provided by Tesaro, Inc.:

Primary Outcome Measures:
  • To evaluate the safety and tolerability of TSR-042 in patients with advanced solid tumors and determine the recommended Phase 2 dose (RP2D) and schedule [ Time Frame: Part 1 and Part 2A Dose Escalation - Approximately 12 months ]
  • To evaluate the antitumor activity of TSR-042 in patients with advanced solid tumors, in terms of objective response rate (ORR) and duration of response (DOR) [ Time Frame: Part 2 Expansion - Approximately 12 months ]

Secondary Outcome Measures:
  • To evaluate the immunogenicity of TSR-042 [ Time Frame: Part 2 - Approximately 12 months ]
  • To determine the pharmacokinetic profile of TSR-042 [ Time Frame: Part 2 - Approximately 24 months ]
  • Immune-related disease control rate (irDCR), duration of response (irDOR) and overall response rate (irORR) based on Investigators' assessment using irRECIST [ Time Frame: Part 2 - Approximately 24 months ]
  • Progression-free survival (PFS) by RECIST v 1.1 and by irRECIST [ Time Frame: Part 2 - Approximately 24 months ]
  • Overall Survival (OS) [ Time Frame: Part 2 - Approximately 24 months ]
  • Patient reported outcome (European Quality of Life scale, 5-Dimensions (EQ-5D-5L) [ Time Frame: Part 2 - Approximately 24 months ]
  • Patient reported outcome (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30)) [ Time Frame: Part 2 - Approximately 24 months ]

Estimated Enrollment: 535
Study Start Date: March 2016
Estimated Study Completion Date: December 2020
Estimated Primary Completion Date: February 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Part 1 - Dose Escalation

Part 1 - Dose Escalation

Part 2 of the study will be conducted in two subparts:

  • In Part 2A, safety and tolerability of TSR-042 at fixed dose will be evaluated.
  • In Part 2B, clinical activity of TSR-042 will be evaluated.
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).

  Eligibility

Information from the National Library of Medicine

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, Learn About Clinical Studies.


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

Inclusion Criteria:

  • Patient is at least 18 years of age
  • Patient with advanced 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: Patient with any advanced or metastatic solid tumor
    2. Part 2A: Patient with any advanced or metastatic solid tumor
    3. Part 2B: Patient with Non-Small Cell Lung Cancer (NSCLC), Endometrial cancers, and MSI-H solid tumors.
  • 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 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.
  • 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.
  Contacts and Locations
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): NCT02715284


Contacts
Contact: Beth Zaharoff, Director, Patient Focus bzaharoff@tesarobio.com

  Show 52 Study Locations
Sponsors and Collaborators
Tesaro, Inc.
  More Information

Responsible Party: Tesaro, Inc.
ClinicalTrials.gov Identifier: NCT02715284     History of Changes
Other Study ID Numbers: 4010-01-001
First Submitted: March 9, 2016
First Posted: March 22, 2016
Last Update Posted: November 17, 2017
Last Verified: November 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Tesaro, Inc.:
Metastatic solid tumors
Advanced solid tumors
anti-PD-1
TSR-042
Immunotherapy
PD-1
Endometrial
Non-small cell lung cancer, NSCLC
MSI-High

Additional relevant MeSH terms:
Neoplasms
Antibodies
Immunoglobulins
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs