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Sym023 (Anti-TIM-3) in Patients With Advanced Solid Tumor Malignancies or Lymphomas

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ClinicalTrials.gov Identifier: NCT03489343
Recruitment Status : Recruiting
First Posted : April 5, 2018
Last Update Posted : January 17, 2019
Sponsor:
Information provided by (Responsible Party):
Symphogen A/S

Brief Summary:
This is the first study to test Sym023 in humans. The primary purpose of this study is to see if Sym023 is safe and tolerable for patients with locally advanced/unresectable or metastatic solid tumor malignancies or lymphomas that are refractory to available therapy or for which no standard therapy is available.

Condition or disease Intervention/treatment Phase
Metastatic Cancer Solid Tumor Lymphoma Drug: Sym023 Phase 1

Detailed Description:
This study will evaluate the preliminary safety, tolerability, and dose-limiting toxicities (DLTs) of Sym023, a recombinant, fully human, anti-T-cell immunoglobulin and mucin-domain containing-3 (anti-TIM-3) monoclonal antibody (mAb). The goal is to establish the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of sequential escalating doses of Sym023 when administered once every 2 weeks (Q2W) by intravenous (IV) infusion to patient cohorts with locally advanced/unresectable or metastatic solid tumor malignancies or lymphomas that are refractory to available therapy or for which no standard therapy is available. If an MTD is not identified, a maximum administered dose (MAD) will be determined. Sym023 will be given to patients in escalating dose cohorts; each patient will be given one fixed dose level.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 48 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1, Open-Label, Multicenter Trial Investigating the Safety, Tolerability, and Preliminary Antineoplastic Activity of Sym023 (Anti-TIM-3) in Patients With Advanced Solid Tumor Malignancies or Lymphomas
Actual Study Start Date : May 30, 2018
Estimated Primary Completion Date : December 2019
Estimated Study Completion Date : September 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma

Arm Intervention/treatment
Experimental: Sym023
Sym023 will be administered at up to 7 planned dose levels.
Drug: Sym023
Sym023 is a recombinant, fully human antibody that binds TIM-3 and induces activation of immune cells.
Other Name: Anti-TIM-3




Primary Outcome Measures :
  1. Assessment of treatment emergent adverse events (AEs) meeting DLT criteria. [ Time Frame: 24 months ]
    Assess the safety and tolerability of Sym023 on a Q2W schedule to establish the MTD and/or RP2D. Assessment based on the occurrence of AEs meeting DLT criteria measured during Cycle 1.


Secondary Outcome Measures :
  1. Evaluation of the immunogenicity of Sym023. [ Time Frame: 24 months ]
    Serum sampling to assess the potential for anti-drug antibody (ADA) formation.

  2. Evaluation of objective response (OR) or stable disease (SD). [ Time Frame: 24 months ]
    Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1), Response Evaluation Criteria in Lymphomas 2017 (RECIL 2017), or Immunotherapeutics Response Evaluation Criteria in Solid Tumors (iRECIST), depending on tumor type.

  3. Time to progression (TTP) of disease. [ Time Frame: 24 months ]
    Based on time of enrollment to first evidence of progression on imaging studies, as assessed by RECIST v1.1, RECIL 2017, or iRECIST, depending on tumor type.

  4. Area under the concentration-time curve in a dosing interval (AUC). [ Time Frame: 24 months ]
    Will be estimated using non-compartmental methods and actual timepoints.

  5. Maximum concentration (Cmax) [ Time Frame: 24 months ]
    Will be derived from observed data.

  6. Time to reach maximum concentration (Tmax) [ Time Frame: 24 months ]
    Will be derived from observed data.

  7. Trough concentration (Ctrough) [ Time Frame: 24 months ]
    Will be derived from observed data.

  8. Terminal elimination half-life (T½) [ Time Frame: 24 months ]
    Will be estimated using non-compartmental methods and actual timepoints.

  9. Clearance (CL) [ Time Frame: 24 months ]
    Will be estimated using non-compartmental methods and actual timepoints.



Information from the National Library of Medicine

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

Inclusion Criteria:

  • Male or female patients, ≥ 18 years of age at the time of obtaining informed consent.
  • Documented (histologically- or cytologically-proven) solid tumor malignancy that is locally advanced or metastatic; patients with documented lymphomas.
  • Malignancy (solid tumor or lymphoma) that is currently not amenable to surgical intervention due to either medical contraindications or nonresectability of the tumor.
  • Refractory to or intolerant of existing therapy(ies) known to provide clinical benefit.
  • Measurable or non-measurable disease according to RECIST v1.1 or RECIL 2017.
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.
  • Not of childbearing potential or who agree to use a highly effective method of contraception during the study beginning within 2 weeks prior to the first dose and continuing until 6 months after the last dose of study drug.

Exclusion Criteria:

  • Women who are pregnant or lactating, or intending to become pregnant before, during, or within 6 months after the last dose of study drug. Women of childbearing potential (WOCBP) and fertile men with WOCBP-partner(s) not using and not willing to use a highly effective method of contraception.
  • Known, untreated central nervous system (CNS) or leptomeningeal metastases, or spinal cord compression, patients with any of the above not controlled by prior surgery or radiotherapy, or patients with symptoms suggesting CNS involvement for which treatment is required.
  • Hematologic malignancies other than lymphomas.
  • Active thrombosis, or a history of deep vein thrombosis (DVT) or pulmonary embolism (PE) within 4 weeks prior to Cycle 1/Day 1 (C1/D1) unless adequately treated and considered stable.
  • Active uncontrolled bleeding or a known bleeding diathesis.
  • Clinically significant cardiovascular disease or condition.
  • Significant ocular disease or condition, including history of autoimmune or inflammatory disorder.
  • Significant pulmonary disease or condition.
  • Current or recent (within 6 months) significant gastrointestinal (GI) disease or condition.
  • An active, known, or suspected autoimmune disease, or a documented history of autoimmune disease or syndrome, requiring systemic steroids or other immunosuppressive medications.
  • History of significant toxicities associated with previous administration of immune checkpoint inhibitors that necessitated permanent discontinuation of that therapy.
  • Patients with unresolved > Grade 1 toxicity associated with any prior antineoplastic therapy.
  • Inadequate recovery from any prior surgical procedure, or having undergone any major surgical procedure within 4 weeks prior to C1/D1.
  • Known history of human immunodeficiency virus (HIV) or known active infection with hepatitis B virus (HBV) or hepatitis C virus (HCV).

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): NCT03489343


Contacts
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Contact: Sara Musalli 908-378-9616 samu@symphogen.com

Locations
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United States, Michigan
South Texas Accelerated Research Therapeutics (START) Midwest Recruiting
Grand Rapids, Michigan, United States, 49503
Contact: Kathy Estkowski, CCRP    616-954-5551    kathy.estkowski@startmidwest.com   
Contact: Yvette C. Cole, RN, BSN, OCN    616-389-1652    yvette.cole@startmidwest.com   
Principal Investigator: Nehal Lakhani, MD, PhD         
United States, Texas
The University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Anjali Raina    713-792-3238    araina@mdanderson.org   
Principal Investigator: Filip Janku, MD, PhD         
NEXT Oncology Recruiting
San Antonio, Texas, United States, 78240
Contact: Sarah Gomez    210-595-5670      
Principal Investigator: Anthony W Tolcher, MD         
Canada, Ontario
Princess Margaret Cancer Centre Recruiting
Toronto, Ontario, Canada, M5G 2M9
Contact: Anna Spreafico, MD    416-946-4501 ext 4012      
Principal Investigator: Anna Spreafico, MD         
Sponsors and Collaborators
Symphogen A/S
Investigators
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Principal Investigator: Lillian Siu, MD, FRCPC Princess Margaret Cancer Centre

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Responsible Party: Symphogen A/S
ClinicalTrials.gov Identifier: NCT03489343     History of Changes
Other Study ID Numbers: Sym023-01
First Posted: April 5, 2018    Key Record Dates
Last Update Posted: January 17, 2019
Last Verified: January 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Symphogen A/S:
Locally advanced/unresectable
Metastatic solid tumor
Lymphoma
Anti-TIM-3
TIM-3
TIM3

Additional relevant MeSH terms:
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Lymphoma
Neoplasm Metastasis
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Neoplastic Processes
Pathologic Processes