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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

NCT02715284

Description:

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.

Related Conditions:
  • Endometrial Carcinoma
  • Malignant Solid Tumor
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief 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
  • 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

Clinical Trial IDs

  • ORG STUDY ID: 4010-01-001
  • NCT ID: NCT02715284

Conditions

  • Advanced or Metastatic Solid Tumors

Interventions

DrugSynonymsArms
TSR-042Part 1 - Dose Escalation

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.

Trial Arms

NameTypeDescriptionInterventions
Part 1 - Dose EscalationExperimentalPart 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.

    Eligibility 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.
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure: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
    Safety Issue:
    Description:

    Secondary Outcome Measures

    Measure:To evaluate the immunogenicity of TSR-042
    Time Frame:Part 2 - Approximately 12 months
    Safety Issue:
    Description:
    Measure:To determine the pharmacokinetic profile of TSR-042
    Time Frame:Part 2 - Approximately 24 months
    Safety Issue:
    Description:
    Measure: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
    Safety Issue:
    Description:
    Measure:Progression-free survival (PFS) by RECIST v 1.1 and by irRECIST
    Time Frame:Part 2 - Approximately 24 months
    Safety Issue:
    Description:
    Measure:Overall Survival (OS)
    Time Frame:Part 2 - Approximately 24 months
    Safety Issue:
    Description:
    Measure:Patient reported outcome (European Quality of Life scale, 5-Dimensions (EQ-5D-5L)
    Time Frame:Part 2 - Approximately 24 months
    Safety Issue:
    Description:
    Measure: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
    Safety Issue:
    Description:

    Details

    Phase:Phase 1
    Primary Purpose:Interventional
    Overall Status:Recruiting
    Lead Sponsor:Tesaro, Inc.

    Trial Keywords

    • Metastatic solid tumors
    • Advanced solid tumors
    • anti-PD-1
    • TSR-042
    • Immunotherapy
    • PD-1
    • Endometrial
    • Non-small cell lung cancer, NSCLC
    • MSI-High

    Last Updated

    November 15, 2017