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Sym022 (Anti-LAG-3) in Patients With Advanced Solid Tumor Malignancies or Lymphomas

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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03489369
Recruitment Status : Completed
First Posted : April 5, 2018
Results First Posted : February 18, 2021
Last Update Posted : February 18, 2021
Sponsor:
Information provided by (Responsible Party):
Symphogen A/S

Brief Summary:
This is the first study to test Sym022 in humans. The primary purpose of this study is to see if Sym022 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: Sym022 Phase 1

Detailed Description:
This study will evaluate the preliminary safety, tolerability, and dose-limiting toxicities (DLTs) of Sym022, an anti-lymphocyte activation gene 3 (anti-LAG-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 Sym022 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. Sym022 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)
Actual Enrollment : 15 participants
Allocation: N/A
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 Sym022 (Anti-LAG-3) in Patients With Advanced Solid Tumor Malignancies or Lymphomas
Actual Study Start Date : May 8, 2018
Actual Primary Completion Date : January 6, 2020
Actual Study Completion Date : January 6, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma

Arm Intervention/treatment
Experimental: Sym022
Sym022 will be administered at up to 4 planned dose levels.
Drug: Sym022
Sym022 is a recombinant, fully human antibody that binds LAG-3 and blocks the LAG-3/major histocompatibility complex class II (MHC-II) interaction, thus allowing for increased T-cell proliferation and cytokine production.
Other Name: Anti-LAG-3




Primary Outcome Measures :
  1. Assessment of Treatment Related Adverse Events (AEs). [ Time Frame: 19 months ]
    Assess the safety, tolerability and dose-limiting toxicities of Sym022 on a Q2W schedule to establish the MTD and/or RP2D.


Secondary Outcome Measures :
  1. Evaluation of the Immunogenicity of Sym022. [ Time Frame: 19 months ]
    Serum sampling and incidence (%) per dose level to assess the potential for anti-drug antibody (ADA) formation. Count of participants show the number of participants who were tested positive for anti-Sym022 ADA.

  2. Evaluation of Objective Response (OR) or Stable Disease (SD). [ Time Frame: 13 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. The numbers shown below correspond to the values related to RECIST v1.1.

  3. Time to Progression (TTP) of Disease. [ Time Frame: 13 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. The numbers shown below correspond to the values related to RECIST v1.1.

  4. Area Under the Concentration-time Curve in a Dosing Interval (AUC). [ Time Frame: 19 months ]
    Will be estimated using non-compartmental methods and actual timepoints.

  5. Maximum Concentration (Cmax) [ Time Frame: 0, 2, 4, 8, 24, 48, 168 hours and 336 hours as administered Q2W (every second week) ]
    Will be derived from observed data.

  6. Time to Reach Maximum Concentration (Tmax) [ Time Frame: 0, 2, 4, 8, 24, 48, 168 hours and 336 hours as administered Q2W (every second week) ]
    Will be derived from observed data.

  7. Trough Concentration (Ctrough) [ Time Frame: 0, 2, 4, 8, 24, 48, 168 hours and 336 hours as administered Q2W (every second week) ]
    Will be derived from observed data.

  8. Terminal Elimination Half-life (T½) [ Time Frame: 0, 2, 4, 8, 24, 48, 168 hours and 336 hours as administered Q2W (every second week) ]
    Will be estimated using non-compartmental methods and actual timepoints.

  9. Clearance (CL) [ Time Frame: 0, 2, 4, 8, 24, 48, 168 hours and 336 hours as administered Q2W (every second week) ]
    Will be estimated using non-compartmental methods and actual timepoints.



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.


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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 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 organ transplantation (e.g. stem cell or solid organ transplant)
  • 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, with exceptions.
  • 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).
  • Other Inhibitors of LAG-3
  • Any antineoplastic agent for the primary malignancy (standard or investigational) without delayed toxicity within 4 weeks or 5 plasma half-lives, whichever is shortest, prior to first administration of study drug and during study
  • Any other investigational treatments within 4 weeks prior to and during study
  • Radiotherapy for target lesions within 4 weeks prior to first administration of study drug unless PD has been documented in the lesion following treatment, and during study.
  • Radiotherapy for non-target lesions within 1 week prior to first administration of study drug
  • Immunosuppressive or systemic hormonal therapy
  • Prophylactic use of hematopoietic growth factors within 1 week prior to first administration of study drug and during Cycle 1 of study

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): NCT03489369


Locations
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United States, Michigan
South Texas Accelerated Research Therapeutics (START) Midwest
Grand Rapids, Michigan, United States, 49503
United States, Texas
The University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030
Canada, Ontario
Princess Margaret Cancer Centre
Toronto, Ontario, Canada, M5G 2M9
Sponsors and Collaborators
Symphogen A/S
Investigators
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Principal Investigator: Lillian Siu, MD, FRCPC Princess Margaret Cancer Centre
  Study Documents (Full-Text)

Documents provided by Symphogen A/S:
Study Protocol  [PDF] April 4, 2019
Statistical Analysis Plan  [PDF] April 13, 2020

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Responsible Party: Symphogen A/S
ClinicalTrials.gov Identifier: NCT03489369    
Other Study ID Numbers: Sym022-01
First Posted: April 5, 2018    Key Record Dates
Results First Posted: February 18, 2021
Last Update Posted: February 18, 2021
Last Verified: February 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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-LAG-3
LAG-3
LAG3
Additional relevant MeSH terms:
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Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases