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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)

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ClinicalTrials.gov Identifier: NCT02715284
Recruitment Status : Recruiting
First Posted : March 22, 2016
Last Update Posted : January 10, 2020
Sponsor:
Information provided by (Responsible Party):
Tesaro, Inc.

Tracking Information
First Submitted Date  ICMJE March 9, 2016
First Posted Date  ICMJE March 22, 2016
Last Update Posted Date January 10, 2020
Actual Study Start Date  ICMJE March 28, 2016
Estimated Primary Completion Date December 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 21, 2019)
  • To evaluate the safety and tolerability of dostarlimab 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 ]
  • Evaluate antitumor activity of dostarlimab in patients with recurrent or advanced mismatch repair deficient/microsatellite instability-high cancers, including dMMR/MSI-H endometrial and non-endometrial dMMR/MSI-H cancers, as to objective response rate [ Time Frame: Part 2 Expansion - Approximately 12 months ]
  • Evaluate antitumor activity of dostarlimab in patients with recurrent or advanced mismatch repair deficient/microsatellite instability-high cancers, including dMMR/MSI-H endometrial and non-endometrial dMMR/MSI-H cancers, as to duration of response [ Time Frame: Part 2 Expansion - Approximately 12 months ]
  • To evaluate the antitumor activity of dostarlimab in patients with recurrent or advanced mismatch repair proficient (MMR-proficient)/microsatellite stable (MSS) endometrial cancer, in terms of objective response rate (ORR). [ Time Frame: Part 2 Expansion - Approximately 12 months ]
  • To evaluate the antitumor activity of dostarlimab in patients with recurrent or advanced mismatch repair proficient (MMR-proficient)/microsatellite stable (MSS) endometrial cancer, in terms of duration of response (DOR). [ Time Frame: Part 2 Expansion - Approximately 12 months ]
  • To evaluate the antitumor activity of dostarlimab in patients with non-small cell lung cancer (NSCLC), in terms of immune-related objective response rate (irORR). [ Time Frame: Part 2 Expansion - Approximately 12 months ]
Original Primary Outcome Measures  ICMJE
 (submitted: March 16, 2016)
  • 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 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 21, 2019)
  • To evaluate the immunogenicity of dostarlimab [ Time Frame: Part 2 - Approximately 12 months ]
  • To assess Area Under the Curve (AUC) [ Time Frame: Part 2 - Approximately 24 months ]
  • To assess Minimum Concentration (Cmin) [ Time Frame: Part 2 - Approximately 24 months ]
  • To assess Maximum Concentration (Cmax) [ Time Frame: Part 2 - Approximately 24 months ]
  • To assess Volume of Distribution (Vz) [ Time Frame: Part 2 - Approximately 24 months ]
  • To assess Clearance (CL) [ Time Frame: Part 2 - Approximately 24 months ]
  • To assess AUC at steady state (AUCss) [ Time Frame: Part 2 - Approximately 24 months ]
  • To assess Cmin at steady state (Cmin,ss) [ Time Frame: Part 2 - Approximately 24 months ]
  • To assess Cmax at steady state (Cmax,ss) [ Time Frame: Part 2 - Approximately 24 months ]
  • To evaluate disease control rate (DCR) [ Time Frame: Part 2 - Approximately 24 months ]
  • To evaluate immune-related disease control rate (irDCR) [ Time Frame: Part 2 - Approximately 24 months ]
  • To evaluate duration of response (DOR) [ Time Frame: Part 2 - Approximately 24 months ]
  • To evaluate immune-related duration of response (irDOR) [ Time Frame: Part 2 - Approximately 24 months ]
  • To evaluate overall response rate (ORR) [ Time Frame: Part 2 - Approximately 24 months ]
  • To evaluate overall immune-related response rate (irORR) [ 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 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: March 16, 2016)
  • 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 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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  ICMJE A Phase 1 Dose Escalation and Cohort Expansion Study of TSR-042, an Anti-PD-1 Monoclonal Antibody, in Patients With Advanced Solid Tumors
Brief Summary This is a multi-center, open-label, first-in-human Phase 1 study evaluating the anti-programmed death receptor 1 (anti-PD-1) antibody dostarlimab (also known as 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 non-endometrial deficient mismatch repair (dMMR)/microsatellite instability-high (MSI-H) solid tumors.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Advanced or Metastatic Solid Tumors
Intervention  ICMJE Biological: dostarlimab
Dostarlimab (also known as 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).
Study Arms  ICMJE 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 dostarlimab at fixed dose will be evaluated.
  • In Part 2B, clinical activity of dostarlimab will be evaluated.
Intervention: Biological: dostarlimab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: August 21, 2019)
740
Original Estimated Enrollment  ICMJE
 (submitted: March 16, 2016)
379
Estimated Study Completion Date  ICMJE December 2023
Estimated Primary Completion Date December 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Patient is at least 18 years of age
  • Patient with advanced or metastatic solid tumor and has disease progression after treatment 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: US GSK Clinical Trials Call Center 877-379-3718 GSKClinicalSupportHD@gsk.com
Contact: EU GSK Clinical Trials Call Center +44 (0) 20 89904466 GSKClinicalSupportHD@gsk.com
Listed Location Countries  ICMJE Canada,   Czechia,   Denmark,   France,   Italy,   Poland,   Spain,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02715284
Other Study ID Numbers  ICMJE 4010-01-001
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Tesaro, Inc.
Study Sponsor  ICMJE Tesaro, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Tesaro, Inc.
Verification Date January 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP