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

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.
 
ClinicalTrials.gov Identifier: NCT02817633
Recruitment Status : Recruiting
First Posted : June 29, 2016
Last Update Posted : May 2, 2022
Sponsor:
Information provided by (Responsible Party):
Tesaro, Inc.

Tracking Information
First Submitted Date  ICMJE June 22, 2016
First Posted Date  ICMJE June 29, 2016
Last Update Posted Date May 2, 2022
Actual Study Start Date  ICMJE July 8, 2016
Estimated Primary Completion Date October 5, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 26, 2022)
  • Part 1 (a): Number of participants achieving dose limiting toxicity (DLTs) [ Time Frame: Up to 28 days ]
  • Part 1 (b,c,d): Number of participants achieving dose limiting toxicity (DLTs) [ Time Frame: Up to 42 days ]
  • Part 1 (f,g,h): Number of participants achieving dose limiting toxicity (DLTs) [ Time Frame: Up to 21 days ]
  • Part 1: Number of participants with adverse events (AEs), serious adverse events (SAEs), AEs leading to discontinuation, treatment emergent adverse events (TEAEs), TEAEs leading to death and immune-related adverse events (irAEs) [ Time Frame: Up to 2 years ]
  • Part 1: Number of participants with clinically significant changes in laboratory parameters, vital signs, electrocardiogram (ECG) findings, Eastern Cooperative Oncology Group (ECOG) status, physical examination and use of concomitant medications [ Time Frame: Up to 2 years ]
  • Part 1 (E) and Part 2: Overall Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 [ Time Frame: Up to 2 years ]
Original Primary Outcome Measures  ICMJE
 (submitted: June 24, 2016)
  • Safety and tolerability of TSR-022 using Common Terminology Criteria for Adverse Events (CTCAE v.4.03) in patients with advanced solid tumors [ Time Frame: Part 1 Dose Escalation - Approximately 2 years ]
  • Anti-tumor activity of TSR-022 in patients with solid tumors, in terms of objective response rate (ORR) as assessed by the Investigators using Response Evaluation Criteria in Solid Tumors (RECIST) v. 1.1 [ Time Frame: Part 2 Expansion - Approximately 2 years ]
  • Recommended Phase 2 dose (RP2D) and schedule as monotherapy and in combination with an anti-PD-1 antibody [ Time Frame: Part 1 and Part 2 - Approximately 4 years ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 26, 2022)
  • Part 1 (c, d, e, f, g, h): Number of participants with anti-TSR-022, anti-TSR-042 [ Time Frame: Up to 2 years ]
  • Part 1 (d): Number of participants with anti-TSR-033 antibodies [ Time Frame: Up to 2 years ]
  • Part 1 (a, b, c, d, f, g, h): ORR by RECIST v 1.1 [ Time Frame: Up to 2 years ]
  • Part 2: ORR by Immune related RECIST (irRECIST) [ Time Frame: Up to 2 years ]
  • Part 2: Duration of response (DOR) by RECIST v 1.1 and irRECIST [ Time Frame: Up to 2 years ]
  • Parts 1 and 2: Disease control rate (DCR) by RECIST v 1.1 [ Time Frame: Up to 2 years ]
  • Part 2: DCR by irRECIST [ Time Frame: Up to 2 years ]
  • Part 2: Progression-free survival (PFS) by RECIST v 1.1 and irRECIST [ Time Frame: Up to 2 years ]
  • Parts 1 and 2: Serum concentration of TSR-022 [ Time Frame: Up to 2 years ]
  • Part 1d: Serum concentration of TSR-033 [ Time Frame: Up to 2 years ]
  • Part 1 (c, d, e, f, g ,h): Serum concentration of TSR-042 [ Time Frame: Up to 2 years ]
  • Part 2: Serum concentration of TSR-042 [ Time Frame: Up to 2 years ]
  • Part 2: Overall survival (OS) [ Time Frame: Up to 2 years ]
  • Part 1a: Minimum plasma concentration (Cmin) of TSR-022 as monotherapy [ Time Frame: Up to 2 years ]
  • Part 1b: Cmin of TSR-022 in combination with nivolumab [ Time Frame: Up to 2 years ]
  • Part 1c: Cmin of TSR-022 in combination with TSR-042 [ Time Frame: Up to 2 years ]
  • Part 1d: Cmin of TSR-022 in combination with TSR-042 and TSR-033 [ Time Frame: Up to 2 years ]
  • Part 1a: Area under the concentration × time curve from time 0 to infinity AUC (0-inf) of TSR-022 as monotherapy [ Time Frame: Up to 2 years ]
  • Part 1b: AUC (0-inf) of TSR-022 in combination with nivolumab [ Time Frame: Up to 2 years ]
  • Part 1c: AUC (0-inf) of TSR-022 in combination with TSR-042 [ Time Frame: Up to 2 years ]
  • Part 1d: AUC (0-inf) of TSR-022 in combination with TSR-042 and TSR-033 [ Time Frame: Up to 2 years ]
  • Part 1a: Area under the concentration time curve from time 0 to last assessment (AUC 0-last) of TSR-022 as monotherapy [ Time Frame: Up to 2 years ]
  • Part 1b: AUC (0-last) of TSR-022 in combination with nivolumab [ Time Frame: Up to 2 years ]
  • Part 1c: AUC (0-last) of TSR-022 in combination with TSR-042 [ Time Frame: Up to 2 years ]
  • Part 1d: AUC (0-last) of TSR-022 in combination with TSR-042 and TSR-033 [ Time Frame: Up to 2 years ]
  • Part 1a: Terminal half life (1/2) of TSR-022 as monotherapy [ Time Frame: Up to 2 years ]
  • Part 1b: t1/2 of TSR-022 and in combination with nivolumab [ Time Frame: Up to 2 years ]
  • Part 1c: t1/2 of TSR-022 in combination with TSR-042 [ Time Frame: Up to 2 years ]
  • Part 1d: t1/2 TSR-022 in combination with TSR-042 and TSR-033 [ Time Frame: Up to 2 years ]
  • Part 1a: Area under the concentration × time curve during the dosing interval (AUCtau) of TSR-022 as monotherapy [ Time Frame: Up to 2 years ]
  • Part 1b: AUCtau of TSR-022 and in combination with nivolumab [ Time Frame: Up to 2 years ]
  • Part 1c: AUCtau of TSR-022 in combination with TSR-042 [ Time Frame: Up to 2 years ]
  • Part 1d: AUCtau of TSR-022 in combination with TSR-042 and TSR-033 [ Time Frame: Up to 2 years ]
  • Part 1: Number of participants with anti-drug antibodies (ADAs) to TSR-022 [ Time Frame: Up to 2 years ]
  • Part 2: Number of participants with ADA to anti-TSR-022 [ Time Frame: Up to 2 years ]
  • Part 1 (c, d, e, f, g ,h): Number of participants with ADA to TSR-042 [ Time Frame: Up to 2 years ]
  • Part 2: Number of Participants with ADA to TSR-042 [ Time Frame: Up to 2 years ]
  • Part 1d: Number of participants with ADA to TSR-033 [ Time Frame: Up to 2 years ]
Original Secondary Outcome Measures  ICMJE
 (submitted: June 24, 2016)
  • Safety and tolerability of TSR-022 using CTCAE v.4.03 [ Time Frame: Part 2 - Approximately 2 years ]
    Incidence of treatment-emergent AEs (TEAEs), SAEs, immune-related AEs (irAEs), TEAEs leading to death, and AEs leading to discontinuation occurring while patients are on treatment or up to 90 days after the last dose of study drug as assessed by CTCAE v4.03
  • Overall Response Rate (ORR) by RECIST v. 1.1 (Part 1) [ Time Frame: Part 1 and Part 2 - Approximately 4 years ]
  • ORR by immune-related RECIST (irRECIST) [ Time Frame: Part 1 and Part 2 - Approximately 4 years ]
  • Duration of response (DOR) by RECIST v 1.1 [ Time Frame: Part 1 and Part 2 - Approximately 4 years ]
  • Disease control rate (DCR) by RECIST v 1.1 and by irRECIST [ Time Frame: Part 1 and Part 2 - Approximately 4 years ]
  • Progression-free survival (PFS) by RECIST v 1.1 and by irRECIST [ Time Frame: Part 1 and Part 2 - Approximately 4 years ]
  • Overall survival (OS) [ Time Frame: Part 1 and Part 2 - Approximately 4 years ]
  • PK Parameter: AUC, 0-last assessment [ Time Frame: Part 1 and Part 2 - Approximately 4 years ]
  • PK Parameter: AUC, 0 to infinity [ Time Frame: Part 1 and Part 2 - Approximately 4 years ]
  • PK Parameter: AUC at steady state [ Time Frame: Part 1 and Part 2 - Approximately 4 years ]
  • PK Parameter: Minimum Concentration (Cmin) [ Time Frame: Part 1 and Part 2 - Approximately 4 years ]
  • PK Parameter: Maximum Concentration (Cmax) [ Time Frame: Part 1 and Part 2 - Approximately 4 years ]
  • PK Parameter: Clearance (CL) [ Time Frame: Part 1 and Part 2 - Approximately 4 years ]
  • PK Parameter: Cmin at steady state (Cmin,ss) [ Time Frame: Part 1 and Part 2 - Approximately 4 years ]
  • PK Parameter: Cmax at steady state (Cmax, ss) [ Time Frame: Part 1 and Part 2 - Approximately 4 years ]
  • PK Parameter: Volume of Distribution (Vz) [ Time Frame: Part 1 and Part 2 - Approximately 4 years ]
  • PK Parameter: terminal half-life (t1/2) [ Time Frame: Part 1 and Part 2 - Approximately 4 years ]
  • Pharmacodynamic profile as assessed by receptor occupancy [ Time Frame: Part 1 and 2 - Approximately 4 years ]
  • Immunogenicity as assessed by the presence of anti-drug antibodies [ Time Frame: Part 1 and 2 -Approximately 4 years ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of TSR-022 in Participants With Advanced Solid Tumors (AMBER)
Official Title  ICMJE A Phase 1 Dose Escalation and Cohort Expansion Study of TSR-022, an Anti-TIM-3 Monoclonal Antibody, in Patients With Advanced Solid Tumors (AMBER)
Brief Summary This is a first-in-human 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 and Part 2 will evaluate the antitumor activity of TSR-022.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description:
This is a multi-center, open-label, first-in-human Phase 1 study.
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Neoplasms
Intervention  ICMJE
  • Drug: TSR-022
    TSR-022 will be administered.
  • Drug: Nivolumab
    Nivolumab will be administered.
  • Drug: TSR-042
    TSR-042 will be administered.
  • Drug: TSR-033
    TSR-033 will be administered.
  • Drug: Docetaxel
    Docetaxel will be administered.
  • Drug: Pemetrexed
  • Drug: Cisplatin
  • Drug: Carboplatin
Study Arms  ICMJE
  • Experimental: Part 1a: TSR-022 monotherapy
    Intervention: Drug: TSR-022
  • Experimental: Part 1b: TSR-022 in combination with nivolumab
    Interventions:
    • Drug: TSR-022
    • Drug: Nivolumab
  • Experimental: Part 1c: TSR-022 in combination with TSR-042
    Interventions:
    • Drug: TSR-022
    • Drug: TSR-042
  • Experimental: Part 1d: TSR-022 in combination with TSR-042 and TSR-033
    Interventions:
    • Drug: TSR-022
    • Drug: TSR-042
    • Drug: TSR-033
  • Experimental: Part 1e: TSR-022 with TSR-042 (not previously treated with anti-programmed death ligand [PD-{L}]1)
    Interventions:
    • Drug: TSR-022
    • Drug: TSR-042
  • Experimental: Part 1f: TSR-022 in combination with TSR-042 and Docetaxel
    Interventions:
    • Drug: TSR-022
    • Drug: TSR-042
    • Drug: Docetaxel
  • Experimental: Part 1g: TSR-022 in combination with TSR-042, pemetrexed, and cisplatin
    Interventions:
    • Drug: TSR-022
    • Drug: TSR-042
    • Drug: Pemetrexed
    • Drug: Cisplatin
  • Experimental: Part 1h: TSR-022 in combination with TSR-042, pemetrexed, and carboplatin
    Interventions:
    • Drug: TSR-022
    • Drug: TSR-042
    • Drug: Pemetrexed
    • Drug: Carboplatin
  • Experimental: Part 2: Cohort A Melanoma-TSR-022 as monotherapy
    Intervention: Drug: TSR-022
  • Experimental: Part 2: Cohort A Melanoma-TSR-022 with TSR-042
    Interventions:
    • Drug: TSR-022
    • Drug: TSR-042
  • Experimental: Part 2:Cohort B Non-small cell lung cancer-TSR-022-monotherapy
    Intervention: Drug: TSR-022
  • Experimental: Part 2:Cohort B Non-small cell lung cancer-TSR-022 with TSR-042
    Interventions:
    • Drug: TSR-022
    • Drug: TSR-042
  • Experimental: Part 2:Cohort C Colorectal cancer-TSR-022 as monotherapy
    Intervention: Drug: TSR-022
  • Experimental: Part 2:Cohort C Colorectal cancer-TSR-022 with TSR-042
    Interventions:
    • Drug: TSR-022
    • Drug: TSR-042
  • Experimental: Part 2: Cohort D-TIM-3 selected non-small cell lung cancer (NSCLC)
    Interventions:
    • Drug: TSR-022
    • Drug: TSR-042
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: July 7, 2020)
369
Original Estimated Enrollment  ICMJE
 (submitted: June 24, 2016)
402
Estimated Study Completion Date  ICMJE October 3, 2024
Estimated Primary Completion Date October 5, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 an ECOG performance status of less than or equal to (<=)1.
  • 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 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
  • 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 (for example [e.g.], cisplatin, carboplatin) and an anti-PD-(L)1 antibody.
  • Participants must have documented radiographic progression by RECIST version 1.1 criteria on prior anti-programmed cell death protein (PD)-1 or anti-PD-(L)1 therapy.
  • Biopsies -All participants enrolled must undergo a biopsy prior to study entry, and the biopsy tissue must be submitted to the central laboratory for all participants in order to determine TIM 3 expression level prior to first dose. 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 greater than or equal to (>=)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.

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-lymphocyte activation gene (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 epidermal growth factor receptor (EGFR) mutation, anaplastic lymphoma kinase (ALK) translocation, or ROS1 mutation.
  • Participant has received a vaccine other than a vaccine against severe acute respiratory syndrome (SARS)-coronavirus 2 (CoV-2) infection ("Coronavirus Disease 2019" [COVID-19]) within 7 days of planned start of study therapy. The use of all COVID-19 vaccines is allowed, with the exception of COVID-19 vaccines using the recombinant adenoviral vector platform within 30 days of planned start of study therapy. If a COVID-19 vaccine using this platform is to be administered within 30 days of planned start of study therapy, this must first be discussed with and approved by the Sponsor's Medical Monitor.
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 Cente 877-379-3718 GSKClinicalSupportHD@gsk.com
Contact: EU GSK Clinical Trials Call Center +44 (0) 20 89904466 GSKClinicalSupportHD@gsk.com
Listed Location Countries  ICMJE Spain,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02817633
Other Study ID Numbers  ICMJE 213348
4020-01-001 ( Other Identifier: Tesaro )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Current Responsible Party Tesaro, Inc.
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Tesaro, Inc.
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: GSK Clinical Trials GlaxoSmithKline
PRS Account Tesaro, Inc.
Verification Date April 2022

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