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

Sponsor
Symphogen A/S (Industry)
Overall Status
Completed
CT.gov ID
NCT03489343
Collaborator
(none)
24
Enrollment
4
Locations
7
Arms
24.3
Actual Duration (Months)
6
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This was the first study to test Sym023 in humans. The primary purpose of this study was 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 DiseaseIntervention/TreatmentPhase
Phase 1

Detailed Description

This study evaluated 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 was 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 was not identified, a maximum administered dose (MAD) was to be determined. Sym023 was given to patients in escalating dose cohorts; each patient was given one fixed dose level.

Study Design

Study Type:
Interventional
Actual Enrollment :
24 participants
Allocation:
Non-Randomized
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 24, 2018
Actual Primary Completion Date :
Jun 3, 2020
Actual Study Completion Date :
Jun 3, 2020

Arms and Interventions

ArmIntervention/Treatment
Experimental: Sym023 0.03 mg/kg

Sym023 was administered at a dose of 0.03 mg/kg by intravenous infusion

Drug: Sym023
Sym023 is a recombinant, fully human antibody that binds TIM-3 and induces activation of immune cells.
Other Names:
  • Anti-TIM-3
  • Experimental: Sym023 0.1 mg/kg

    Sym023 was administered at a dose of 0.1 mg/kg by intravenous infusion

    Drug: Sym023
    Sym023 is a recombinant, fully human antibody that binds TIM-3 and induces activation of immune cells.
    Other Names:
  • Anti-TIM-3
  • Experimental: Sym023 0.3 mg/kg

    Sym023 was administered at a dose of 0.3 mg/kg by intravenous infusion

    Drug: Sym023
    Sym023 is a recombinant, fully human antibody that binds TIM-3 and induces activation of immune cells.
    Other Names:
  • Anti-TIM-3
  • Experimental: Sym023 1.0 mg/kg

    Sym023 was administered at a dose of 1.0 mg/kg by intravenous infusion

    Drug: Sym023
    Sym023 is a recombinant, fully human antibody that binds TIM-3 and induces activation of immune cells.
    Other Names:
  • Anti-TIM-3
  • Experimental: Sym023 3.0 mg/kg

    Sym023 was administered at a dose of 3.0 mg/kg by intravenous infusion

    Drug: Sym023
    Sym023 is a recombinant, fully human antibody that binds TIM-3 and induces activation of immune cells.
    Other Names:
  • Anti-TIM-3
  • Experimental: Sym023 10.0 mg/kg

    Sym023 was administered at a dose of 10.0 mg/kg by intravenous infusion

    Drug: Sym023
    Sym023 is a recombinant, fully human antibody that binds TIM-3 and induces activation of immune cells.
    Other Names:
  • Anti-TIM-3
  • Experimental: Sym023 20.0 mg/kg

    Sym023 was administered at a dose of 20.0 mg/kg by intravenous infusion

    Drug: Sym023
    Sym023 is a recombinant, fully human antibody that binds TIM-3 and induces activation of immune cells.
    Other Names:
  • Anti-TIM-3
  • Outcome Measures

    Primary Outcome Measures

    1. Assessment of Treatment Emergent Adverse Events (AEs) Meeting Dose-limiting Toxicity (DLT) Criteria. [28 days]

      Assess the safety and tolerability of Sym023 on a Q2W (once every 2 weeks) schedule to establish the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D). Assessment based on the occurrence of AEs meeting DLT criteria measured during Cycle 1. The MTD was to be determined by those DLTs that occurred during C1 in either more than 1 patient in a 3 to 6 patient cohort or ≥33.3% of patients in the event of an expanded 7 to 12 patient cohort. One patient in the 10.0 mg/kg dose cohort was not evaluable for MTD as she did not complete C1 for a reason other than drug toxicity (i.e., discontinuation after 1 dose due to patient withdrawal of consent). However, this patient was included in the evaluation of other outcomes.

    Secondary Outcome Measures

    1. Evaluation of the Immunogenicity of Sym023. [Baseline up to 6-months follow-up, approximately 1 year]

      Serum sampling to assess the potential for anti-drug antibody (ADA) formation. The number of patients with positive samples at indicated visits is presented.

    2. Evaluation of Objective Response (OR) or Stable Disease (SD) by RECIST v1.1 [24 months]

      OR or SD Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1). The number of patients with confirmed or unconfirmed OR (partial or complete response) is presented. Duration of SD for patients with best overall response = SD was defined as the time from the day of first study treatment to the start of radiologic disease progression or death. If the patient did not have a radiological disease progression or death, the duration of SD was defined as the time from the day of first study treatment to the date of the last SD assessment.

    3. Evaluation of Objective Response (OR) or Stable Disease (SD) by iRECIST [24 months]

      OR or SD Assessed by Immunotherapeutics Response Evaluation Criteria in Solid Tumors (iRECIST). The number of patients with confirmed or unconfirmed OR (partial or complete response) is presented. Duration of SD for patients with best overall response = SD was defined as the time from the day of first study treatment to the start of radiologic disease progression or death. If the patient did not have a radiological disease progression or death, the duration of SD was defined as the time from the day of first study treatment to the date of the last SD assessment.

    4. Evaluation of Objective Response (OR) or Stable Disease (SD) by RECIL 2017. [24 months]

      OR or SD Assessed by Response Evaluation Criteria in Lymphomas 2017 (RECIL 2017)

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

    6. Area Under the Concentration-time Curve in a Dosing Interval (AUC). [From before the start of the infusion to 168 hours after the end of the infusion]

      The AUC after first dose was estimated using non-compartmental methods. Blood samples for PK analysis were taken at the following timepoints: before the start of the infusion, at the end of the infusion and at 2, 4, 8, 24, 48 and 168 hours after the end of the infusion. Actual timepoints were recorded.

    7. Maximum Concentration (Cmax) [From before the start of the infusion to 168 hours after the end of the infusion]

      Outcome measure after first dose was derived from observed data. Blood samples for PK analysis were taken at the following timepoints: before the start of the infusion, at the end of the infusion and at 2, 4, 8, 24, 48 and 168 hours after the end of the infusion. Actual timepoints were recorded.

    8. Time to Reach Maximum Concentration (Tmax) [From before the start of the infusion to 168 hours after the end of the infusion]

      Outcome measure after first dose was derived from observed data. Blood samples for PK analysis were taken at the following timepoints: before the start of the infusion, at the end of the infusion and at 2, 4, 8, 24, 48 and 168 hours after the end of the infusion. Actual timepoints were recorded.

    9. Trough Concentration (Ctrough) [From before the start of the infusion to 168 hours after the end of the infusion]

      Outcome measure after first dose was derived from observed data. Blood samples for PK analysis were taken at the following timepoints: before the start of the infusion, at the end of the infusion and at 2, 4, 8, 24, 48 and 168 hours after the end of the infusion. Actual timepoints were recorded.

    10. Terminal Elimination Half-life (T½) [From before the start of the infusion to 168 hours after the end of the infusion]

      Outcome measure after first dose was estimated using non-compartmental methods. Blood samples for PK analysis were taken at the following timepoints: before the start of the infusion, at the end of the infusion and at 2, 4, 8, 24, 48 and 168 hours after the end of the infusion. Actual timepoints were recorded.

    11. Clearance (CL) [From before the start of the infusion to 168 hours after the end of the infusion]

      Outcome measure after first dose was estimated using non-compartmental methods. Blood samples for PK analysis were taken at the following timepoints: before the start of the infusion, at the end of the infusion and at 2, 4, 8, 24, 48 and 168 hours after the end of the infusion. Actual timepoints were recorded.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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, 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).

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1South Texas Accelerated Research Therapeutics (START) MidwestGrand RapidsMichiganUnited States49503
    2The University of Texas MD Anderson Cancer CenterHoustonTexasUnited States77030
    3NEXT OncologySan AntonioTexasUnited States78240
    4Princess Margaret Cancer CentreTorontoOntarioCanadaM5G 2M9

    Sponsors and Collaborators

    • Symphogen A/S

    Investigators

    • Principal Investigator: Lillian Siu, MD, FRCPC, Princess Margaret Cancer Centre

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Symphogen A/S
    ClinicalTrials.gov Identifier:
    NCT03489343
    Other Study ID Numbers:
    • Sym023-01
    First Posted:
    Apr 5, 2018
    Last Update Posted:
    Oct 12, 2021
    Last Verified:
    Aug 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Symphogen A/S
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group TitleSym023 0.03 mg/kgSym023 0.1 mg/kgSym023 0.3 mg/kgSym023 1.0 mg/kgSym023 3.0 mg/kgSym023 10.0 mg/kgSym023 20.0 mg/kg
    Arm/Group DescriptionSym023 0.03 mg/kg intravenous infusion once every 2 weeksSym023 0.1 mg/kg intravenous infusion once every 2 weeksSym023 0.3 mg/kg intravenous infusion once every 2 weeksSym023 1.0 mg/kg intravenous infusion once every 2 weeksSym023 3.0 mg/kg intravenous infusion once every 2 weeksSym023 10.0 mg/kg intravenous infusion once every 2 weeksSym023 20.0 mg/kg intravenous infusion once every 2 weeks
    Period Title: Overall Study
    STARTED1133376
    COMPLETED0000000
    NOT COMPLETED1133376

    Baseline Characteristics

    Arm/Group TitleSym023 0.03 mg/kgSym023 0.1 mg/kgSym023 0.3 mg/kgSym023 1.0 mg/kgSym023 3.0 mg/kgSym023 10.0 mg/kgSym023 20.0 mg/kgTotal
    Arm/Group DescriptionSym023 0.03 mg/kg intravenous infusion once every 2 weeksSym023 0.1 mg/kg intravenous infusion once every 2 weeksSym023 0.3 mg/kg intravenous infusion once every 2 weeksSym023 1.0 mg/kg intravenous infusion once every 2 weeksSym023 3.0 mg/kg intravenous infusion once every 2 weeksSym023 10.0 mg/kg intravenous infusion once every 2 weeksSym023 20.0 mg/kg intravenous infusion once every 2 weeksTotal of all reporting groups
    Overall Participants113337624
    Age (Count of Participants)
    <=18 years
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Between 18 and 65 years
    1
    100%
    1
    100%
    2
    66.7%
    1
    33.3%
    1
    33.3%
    5
    71.4%
    5
    83.3%
    16
    66.7%
    >=65 years
    0
    0%
    0
    0%
    1
    33.3%
    2
    66.7%
    2
    66.7%
    2
    28.6%
    1
    16.7%
    8
    33.3%
    Age (years) [Median (Full Range) ]
    Median (Full Range) [years]
    64
    64
    62
    66
    71
    54
    61
    63
    Sex: Female, Male (Count of Participants)
    Female
    0
    0%
    1
    100%
    2
    66.7%
    2
    66.7%
    3
    100%
    4
    57.1%
    4
    66.7%
    16
    66.7%
    Male
    1
    100%
    0
    0%
    1
    33.3%
    1
    33.3%
    0
    0%
    3
    42.9%
    2
    33.3%
    8
    33.3%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Not Hispanic or Latino
    1
    100%
    1
    100%
    3
    100%
    3
    100%
    2
    66.7%
    7
    100%
    6
    100%
    23
    95.8%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    33.3%
    0
    0%
    0
    0%
    1
    4.2%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Asian
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    3
    42.9%
    0
    0%
    3
    12.5%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    2
    28.6%
    1
    16.7%
    3
    12.5%
    White
    1
    100%
    1
    100%
    3
    100%
    3
    100%
    2
    66.7%
    2
    28.6%
    5
    83.3%
    17
    70.8%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    33.3%
    0
    0%
    0
    0%
    1
    4.2%
    Region of Enrollment (participants) [Number]
    Canada
    0
    0%
    0
    0%
    0
    0%
    1
    33.3%
    1
    33.3%
    2
    28.6%
    1
    16.7%
    5
    20.8%
    United States
    1
    100%
    1
    100%
    3
    100%
    2
    66.7%
    2
    66.7%
    5
    71.4%
    5
    83.3%
    19
    79.2%
    ECOG PS (Count of Participants)
    1
    1
    100%
    1
    100%
    2
    66.7%
    2
    66.7%
    3
    100%
    6
    85.7%
    4
    66.7%
    19
    79.2%
    0
    0
    0%
    0
    0%
    1
    33.3%
    1
    33.3%
    0
    0%
    1
    14.3%
    2
    33.3%
    5
    20.8%

    Outcome Measures

    1. Primary Outcome
    TitleAssessment of Treatment Emergent Adverse Events (AEs) Meeting Dose-limiting Toxicity (DLT) Criteria.
    DescriptionAssess the safety and tolerability of Sym023 on a Q2W (once every 2 weeks) schedule to establish the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D). Assessment based on the occurrence of AEs meeting DLT criteria measured during Cycle 1. The MTD was to be determined by those DLTs that occurred during C1 in either more than 1 patient in a 3 to 6 patient cohort or ≥33.3% of patients in the event of an expanded 7 to 12 patient cohort. One patient in the 10.0 mg/kg dose cohort was not evaluable for MTD as she did not complete C1 for a reason other than drug toxicity (i.e., discontinuation after 1 dose due to patient withdrawal of consent). However, this patient was included in the evaluation of other outcomes.
    Time Frame28 days

    Outcome Measure Data

    Analysis Population Description
    DLT analysis set of patients who completed treatment dosing in a 4-week (28 day) period that was Cycle 1. One patient out of 7 patients in Group 10mg/kg did not complete Cycle 1 and are not included in the "participants analyzed"
    Arm/Group TitleSym023 0.03 mg/kgSym023 0.1 mg/kgSym023 0.3 mg/kgSym023 1.0 mg/kgSym023 3.0 mg/kgSym023 10.0 mg/kgSym023 20.0 mg/kg
    Arm/Group DescriptionSym023 0.03 mg/kg intravenous infusion once every 2 weeksSym023 0.1 mg/kg intravenous infusion once every 2 weeksSym023 0.3 mg/kg intravenous infusion once every 2 weeksSym023 1.0 mg/kg intravenous infusion once every 2 weeksSym023 3.0 mg/kg intravenous infusion once every 2 weeksSym023 10.0 mg/kg intravenous infusion once every 2 weeksSym023 20.0 mg/kg intravenous infusion once every 2 weeks
    Measure Participants1133366
    Number [Number of DLTs]
    0
    0
    0
    0
    0
    0
    0
    2. Secondary Outcome
    TitleEvaluation of the Immunogenicity of Sym023.
    DescriptionSerum sampling to assess the potential for anti-drug antibody (ADA) formation. The number of patients with positive samples at indicated visits is presented.
    Time FrameBaseline up to 6-months follow-up, approximately 1 year

    Outcome Measure Data

    Analysis Population Description
    Full analysis set of all randomised and treated patients
    Arm/Group TitleSym023 0.03 mg/kgSym023 0.1 mg/kgSym023 0.3 mg/kgSym023 1.0 mg/kgSym023 3.0 mg/kgSym023 10.0 mg/kgSym023 20.0 mg/kg
    Arm/Group DescriptionSym023 0.03 mg/kg intravenous infusion once every 2 weeksSym023 0.1 mg/kg intravenous infusion once every 2 weeksSym023 0.3 mg/kg intravenous infusion once every 2 weeksSym023 1.0 mg/kg intravenous infusion once every 2 weeksSym023 3.0 mg/kg intravenous infusion once every 2 weeksSym023 10.0 mg/kg intravenous infusion once every 2 weeksSym023 20.0 mg/kg intravenous infusion once every 2 weeks
    Measure Participants1133376
    Cycle 1 days 1 and 15
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Cycle 2 day 1
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Cycle 3 days 1 and 15
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Cycle 4 days 1 and 15
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Cycle 5 day 1
    0
    0%
    1
    100%
    0
    0%
    1
    33.3%
    0
    0%
    0
    0%
    0
    0%
    Cycle 6 day 1
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Cycle 7 day 1
    0
    0%
    1
    100%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    End of treatment
    0
    0%
    1
    100%
    1
    33.3%
    1
    33.3%
    0
    0%
    0
    0%
    0
    0%
    1-month follow up
    0
    0%
    1
    100%
    1
    33.3%
    1
    33.3%
    0
    0%
    0
    0%
    0
    0%
    3-month follow up
    0
    0%
    0
    0%
    0
    0%
    1
    33.3%
    0
    0%
    0
    0%
    0
    0%
    3. Secondary Outcome
    TitleEvaluation of Objective Response (OR) or Stable Disease (SD) by RECIST v1.1
    DescriptionOR or SD Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1). The number of patients with confirmed or unconfirmed OR (partial or complete response) is presented. Duration of SD for patients with best overall response = SD was defined as the time from the day of first study treatment to the start of radiologic disease progression or death. If the patient did not have a radiological disease progression or death, the duration of SD was defined as the time from the day of first study treatment to the date of the last SD assessment.
    Time Frame24 months

    Outcome Measure Data

    Analysis Population Description
    Full analysis set of randomised and treated patients who was evaluable for response. One patient out of 7 in group 10mg/kg was not evaluable for response
    Arm/Group TitleSym023 0.03 mg/kgSym023 0.1 mg/kgSym023 0.3 mg/kgSym023 1.0 mg/kgSym023 3.0 mg/kgSym023 10.0 mg/kgSym023 20.0 mg/kg
    Arm/Group DescriptionSym023 0.03 mg/kg intravenous infusion once every 2 weeksSym023 0.1 mg/kg intravenous infusion once every 2 weeksSym023 0.3 mg/kg intravenous infusion once every 2 weeksSym023 1.0 mg/kg intravenous infusion once every 2 weeksSym023 3.0 mg/kg intravenous infusion once every 2 weeksSym023 10.0 mg/kg intravenous infusion once every 2 weeksSym023 20.0 mg/kg intravenous infusion once every 2 weeks
    Measure Participants1133366
    OR rate
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    SD >16 weeks
    0
    0%
    1
    100%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    2
    33.3%
    SD ≤16 weeks
    0
    0%
    0
    0%
    0
    0%
    2
    66.7%
    2
    66.7%
    0
    0%
    3
    50%
    4. Secondary Outcome
    TitleEvaluation of Objective Response (OR) or Stable Disease (SD) by iRECIST
    DescriptionOR or SD Assessed by Immunotherapeutics Response Evaluation Criteria in Solid Tumors (iRECIST). The number of patients with confirmed or unconfirmed OR (partial or complete response) is presented. Duration of SD for patients with best overall response = SD was defined as the time from the day of first study treatment to the start of radiologic disease progression or death. If the patient did not have a radiological disease progression or death, the duration of SD was defined as the time from the day of first study treatment to the date of the last SD assessment.
    Time Frame24 months

    Outcome Measure Data

    Analysis Population Description
    Full analysis set of randomised and treated patients who were evaluable for response. One patient out of 7 in group 10mg/kg was not evaluable for response
    Arm/Group TitleSym023 0.03 mg/kgSym023 0.1 mg/kgSym023 0.3 mg/kgSym023 1.0 mg/kgSym023 3.0 mg/kgSym023 10.0 mg/kgSym023 20.0 mg/kg
    Arm/Group DescriptionSym023 0.03 mg/kg intravenous infusion once every 2 weeksSym023 0.1 mg/kg intravenous infusion once every 2 weeksSym023 0.3 mg/kg intravenous infusion once every 2 weeksSym023 1.0 mg/kg intravenous infusion once every 2 weeksSym023 3.0 mg/kg intravenous infusion once every 2 weeksSym023 10.0 mg/kg intravenous infusion once every 2 weeksSym023 20.0 mg/kg intravenous infusion once every 2 weeks
    Measure Participants1133366
    OR rate
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    iSD >16 weeks
    0
    0%
    1
    100%
    0
    0%
    1
    33.3%
    1
    33.3%
    0
    0%
    1
    16.7%
    iSD ≤16 weeks
    0
    0%
    0
    0%
    0
    0%
    2
    66.7%
    1
    33.3%
    0
    0%
    4
    66.7%
    5. Secondary Outcome
    TitleEvaluation of Objective Response (OR) or Stable Disease (SD) by RECIL 2017.
    DescriptionOR or SD Assessed by Response Evaluation Criteria in Lymphomas 2017 (RECIL 2017)
    Time Frame24 months

    Outcome Measure Data

    Analysis Population Description
    No lymphomas were recorded in this trial, therefore it was not possible to do the RECIL evaluation.
    Arm/Group TitleSym023 0.03 mg/kgSym023 0.1 mg/kgSym023 0.3 mg/kgSym023 1.0 mg/kgSym023 3.0 mg/kgSym023 10.0 mg/kgSym023 20.0 mg/kg
    Arm/Group DescriptionSym023 0.03 mg/kg intravenous infusion once every 2 weeksSym023 0.1 mg/kg intravenous infusion once every 2 weeksSym023 0.3 mg/kg intravenous infusion once every 2 weeksSym023 1.0 mg/kg intravenous infusion once every 2 weeksSym023 3.0 mg/kg intravenous infusion once every 2 weeksSym023 10.0 mg/kg intravenous infusion once every 2 weeksSym023 20.0 mg/kg intravenous infusion once every 2 weeks
    Measure Participants0000000
    6. Secondary Outcome
    TitleTime to Progression (TTP) of Disease.
    DescriptionBased 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.
    Time Frame24 months

    Outcome Measure Data

    Analysis Population Description
    The full analysis set of randomized and treated patients who were evaluable for response. One patient out of 7 in group 10mg/kg was not evaluable for response or time to progression (TTP) as the patient left trial due to Adverse Event
    Arm/Group TitleSym023 0.03 mg/kgSym023 0.1 mg/kgSym023 0.3 mg/kgSym023 1.0 mg/kgSym023 3.0 mg/kgSym023 10.0 mg/kgSym023 20.0 mg/kg
    Arm/Group DescriptionSym023 0.03 mg/kg intravenous infusion once every 2 weeksSym023 0.1 mg/kg intravenous infusion once every 2 weeksSym023 0.3 mg/kg intravenous infusion once every 2 weeksSym023 1.0 mg/kg intravenous infusion once every 2 weeksSym023 3.0 mg/kg intravenous infusion once every 2 weeksSym023 10.0 mg/kg intravenous infusion once every 2 weeksSym023 20.0 mg/kg intravenous infusion once every 2 weeks
    Measure Participants1133366
    Median (Full Range) [months]
    1.81
    7.89
    1.18
    3.48
    1.28
    1.68
    5.36
    7. Secondary Outcome
    TitleArea Under the Concentration-time Curve in a Dosing Interval (AUC).
    DescriptionThe AUC after first dose was estimated using non-compartmental methods. Blood samples for PK analysis were taken at the following timepoints: before the start of the infusion, at the end of the infusion and at 2, 4, 8, 24, 48 and 168 hours after the end of the infusion. Actual timepoints were recorded.
    Time FrameFrom before the start of the infusion to 168 hours after the end of the infusion

    Outcome Measure Data

    Analysis Population Description
    Pharmacokinetic analysis set (same as the full analysis set) of all randomised and treated patients
    Arm/Group TitleSym023 0.03 mg/kgSym023 0.1 mg/kgSym023 0.3 mg/kgSym023 1.0 mg/kgSym023 3.0 mg/kgSym023 10.0 mg/kgSym023 20.0 mg/kg
    Arm/Group DescriptionSym023 0.03 mg/kg intravenous infusion once every 2 weeksSym023 0.1 mg/kg intravenous infusion once every 2 weeksSym023 0.3 mg/kg intravenous infusion once every 2 weeksSym023 1.0 mg/kg intravenous infusion once every 2 weeksSym023 3.0 mg/kg intravenous infusion once every 2 weeksSym023 10.0 mg/kg intravenous infusion once every 2 weeksSym023 20.0 mg/kg intravenous infusion once every 2 weeks
    Measure Participants1133376
    Mean (Full Range) [h*μg/mL]
    70
    176
    878
    3193
    8062
    30581
    77262
    8. Secondary Outcome
    TitleMaximum Concentration (Cmax)
    DescriptionOutcome measure after first dose was derived from observed data. Blood samples for PK analysis were taken at the following timepoints: before the start of the infusion, at the end of the infusion and at 2, 4, 8, 24, 48 and 168 hours after the end of the infusion. Actual timepoints were recorded.
    Time FrameFrom before the start of the infusion to 168 hours after the end of the infusion

    Outcome Measure Data

    Analysis Population Description
    Pharmacokinetic analysis set (same as the full analysis set) of all randomised and treated patients
    Arm/Group TitleSym023 0.03 mg/kgSym023 0.1 mg/kgSym023 0.3 mg/kgSym023 1.0 mg/kgSym023 3.0 mg/kgSym023 10.0 mg/kgSym023 20.0 mg/kg
    Arm/Group DescriptionSym023 0.03 mg/kg intravenous infusion once every 2 weeksSym023 0.1 mg/kg intravenous infusion once every 2 weeksSym023 0.3 mg/kg intravenous infusion once every 2 weeksSym023 1.0 mg/kg intravenous infusion once every 2 weeksSym023 3.0 mg/kg intravenous infusion once every 2 weeksSym023 10.0 mg/kg intravenous infusion once every 2 weeksSym023 20.0 mg/kg intravenous infusion once every 2 weeks
    Measure Participants1133376
    Mean (Full Range) [μg/mL]
    0.85
    1.98
    7.94
    23.71
    68.03
    232.11
    470.24
    9. Secondary Outcome
    TitleTime to Reach Maximum Concentration (Tmax)
    DescriptionOutcome measure after first dose was derived from observed data. Blood samples for PK analysis were taken at the following timepoints: before the start of the infusion, at the end of the infusion and at 2, 4, 8, 24, 48 and 168 hours after the end of the infusion. Actual timepoints were recorded.
    Time FrameFrom before the start of the infusion to 168 hours after the end of the infusion

    Outcome Measure Data

    Analysis Population Description
    Pharmacokinetic analysis set (same as the full analysis set) of all randomised and treated patients
    Arm/Group TitleSym023 0.03 mg/kgSym023 0.1 mg/kgSym023 0.3 mg/kgSym023 1.0 mg/kgSym023 3.0 mg/kgSym023 10.0 mg/kgSym023 20.0 mg/kg
    Arm/Group DescriptionSym023 0.03 mg/kg intravenous infusion once every 2 weeksSym023 0.1 mg/kg intravenous infusion once every 2 weeksSym023 0.3 mg/kg intravenous infusion once every 2 weeksSym023 1.0 mg/kg intravenous infusion once every 2 weeksSym023 3.0 mg/kg intravenous infusion once every 2 weeksSym023 10.0 mg/kg intravenous infusion once every 2 weeksSym023 20.0 mg/kg intravenous infusion once every 2 weeks
    Measure Participants1133376
    Mean (Full Range) [hours]
    4.5
    0.6
    1.2
    4.5
    1.8
    3.4
    7.3
    10. Secondary Outcome
    TitleTrough Concentration (Ctrough)
    DescriptionOutcome measure after first dose was derived from observed data. Blood samples for PK analysis were taken at the following timepoints: before the start of the infusion, at the end of the infusion and at 2, 4, 8, 24, 48 and 168 hours after the end of the infusion. Actual timepoints were recorded.
    Time FrameFrom before the start of the infusion to 168 hours after the end of the infusion

    Outcome Measure Data

    Analysis Population Description
    Pharmacokinetic analysis set (same as the full analysis set) of all randomized and treated patients. Data for cohort 0.03mg/kg: Ctrough at 168 hours were below the limit of quantification, hence no reported data
    Arm/Group TitleSym023 0.03 mg/kgSym023 0.1 mg/kgSym023 0.3 mg/kgSym023 1.0 mg/kgSym023 3.0 mg/kgSym023 10.0 mg/kgSym023 20.0 mg/kg
    Arm/Group DescriptionSym023 0.03 mg/kg intravenous infusion once every 2 weeksSym023 0.1 mg/kg intravenous infusion once every 2 weeksSym023 0.3 mg/kg intravenous infusion once every 2 weeksSym023 1.0 mg/kg intravenous infusion once every 2 weeksSym023 3.0 mg/kg intravenous infusion once every 2 weeksSym023 10.0 mg/kg intravenous infusion once every 2 weeksSym023 20.0 mg/kg intravenous infusion once every 2 weeks
    Measure Participants1133356
    Mean (Full Range) [μg/mL]
    NA
    0.16
    1.26
    6.39
    12.88
    74.33
    146.96
    11. Secondary Outcome
    TitleTerminal Elimination Half-life (T½)
    DescriptionOutcome measure after first dose was estimated using non-compartmental methods. Blood samples for PK analysis were taken at the following timepoints: before the start of the infusion, at the end of the infusion and at 2, 4, 8, 24, 48 and 168 hours after the end of the infusion. Actual timepoints were recorded.
    Time FrameFrom before the start of the infusion to 168 hours after the end of the infusion

    Outcome Measure Data

    Analysis Population Description
    Pharmacokinetic analysis set (same as the full analysis set) of all randomised and treated patients. Data for cohort 0.03mg/kg: T½ could not be accurately calculated due to few datapoint within the elimination period
    Arm/Group TitleSym023 0.03 mg/kgSym023 0.1 mg/kgSym023 0.3 mg/kgSym023 1.0 mg/kgSym023 3.0 mg/kgSym023 10.0 mg/kgSym023 20.0 mg/kg
    Arm/Group DescriptionSym023 0.03 mg/kg intravenous infusion once every 2 weeksSym023 0.1 mg/kg intravenous infusion once every 2 weeksSym023 0.3 mg/kg intravenous infusion once every 2 weeksSym023 1.0 mg/kg intravenous infusion once every 2 weeksSym023 3.0 mg/kg intravenous infusion once every 2 weeksSym023 10.0 mg/kg intravenous infusion once every 2 weeksSym023 20.0 mg/kg intravenous infusion once every 2 weeks
    Measure Participants1130221
    Mean (Full Range) [hours]
    NA
    105.10
    153.49
    140.60
    185.22
    203.07
    12. Secondary Outcome
    TitleClearance (CL)
    DescriptionOutcome measure after first dose was estimated using non-compartmental methods. Blood samples for PK analysis were taken at the following timepoints: before the start of the infusion, at the end of the infusion and at 2, 4, 8, 24, 48 and 168 hours after the end of the infusion. Actual timepoints were recorded.
    Time FrameFrom before the start of the infusion to 168 hours after the end of the infusion

    Outcome Measure Data

    Analysis Population Description
    Pharmacokinetic analysis set (same as the full analysis set) of all randomized and treated patients. Data for cohort 0.03mg/kg: Clearence could not be accurately calculated since too few datapoint within the elimination period
    Arm/Group TitleSym023 0.03 mg/kgSym023 0.1 mg/kgSym023 0.3 mg/kgSym023 1.0 mg/kgSym023 3.0 mg/kgSym023 10.0 mg/kgSym023 20.0 mg/kg
    Arm/Group DescriptionSym023 0.03 mg/kg intravenous infusion once every 2 weeksSym023 0.1 mg/kg intravenous infusion once every 2 weeksSym023 0.3 mg/kg intravenous infusion once every 2 weeksSym023 1.0 mg/kg intravenous infusion once every 2 weeksSym023 3.0 mg/kg intravenous infusion once every 2 weeksSym023 10.0 mg/kg intravenous infusion once every 2 weeksSym023 20.0 mg/kg intravenous infusion once every 2 weeks
    Measure Participants0110100
    Mean (Full Range) [mL/h)/kg]
    0.501
    0.364
    0.582

    Adverse Events

    Time Frame24 months
    Adverse Event Reporting Description Only treatment-emergent adverse events (AEs) are presented in clinicaltrials.gov, defined as AEs with onset dates on or after the first dose of study medication or AEs that occurred before the first dose of study medication and increased in severity after the first dose of study medication up to the last dose of study drug plus 30 days.
    Arm/Group TitleSym023 0.03 mg/kgSym023 0.1 mg/kgSym023 0.3 mg/kgSym023 1.0 mg/kgSym023 3.0 mg/kgSym023 10.0 mg/kgSym023 20.0 mg/kg
    Arm/Group DescriptionSym023 0.03 mg/kg intravenous infusion once every 2 weeksSym023 0.1 mg/kg intravenous infusion once every 2 weeksSym023 0.3 mg/kg intravenous infusion once every 2 weeksSym023 1.0 mg/kg intravenous infusion once every 2 weeksSym023 3.0 mg/kg intravenous infusion once every 2 weeksSym023 10.0 mg/kg intravenous infusion once every 2 weeksSym023 20.0 mg/kg intravenous infusion once every 2 weeks
    All Cause Mortality
    Sym023 0.03 mg/kgSym023 0.1 mg/kgSym023 0.3 mg/kgSym023 1.0 mg/kgSym023 3.0 mg/kgSym023 10.0 mg/kgSym023 20.0 mg/kg
    Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total0/1 (0%) 0/1 (0%) 3/3 (100%) 0/3 (0%) 2/3 (66.7%) 1/7 (14.3%) 1/6 (16.7%)
    Serious Adverse Events
    Sym023 0.03 mg/kgSym023 0.1 mg/kgSym023 0.3 mg/kgSym023 1.0 mg/kgSym023 3.0 mg/kgSym023 10.0 mg/kgSym023 20.0 mg/kg
    Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total0/1 (0%) 1/1 (100%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 2/7 (28.6%) 1/6 (16.7%)
    Investigations
    Lipase increased0/1 (0%) 00/1 (0%) 00/3 (0%) 00/3 (0%) 00/3 (0%) 01/7 (14.3%) 10/6 (0%) 0
    Musculoskeletal and connective tissue disorders
    Immune-mediated arthritis0/1 (0%) 01/1 (100%) 10/3 (0%) 00/3 (0%) 00/3 (0%) 00/7 (0%) 00/6 (0%) 0
    Pathological fracture0/1 (0%) 00/1 (0%) 00/3 (0%) 00/3 (0%) 00/3 (0%) 01/7 (14.3%) 10/6 (0%) 0
    Back pain0/1 (0%) 00/1 (0%) 00/3 (0%) 00/3 (0%) 00/3 (0%) 00/7 (0%) 01/6 (16.7%) 1
    Nervous system disorders
    Spinal cord compression0/1 (0%) 00/1 (0%) 00/3 (0%) 00/3 (0%) 00/3 (0%) 00/7 (0%) 01/6 (16.7%) 1
    Other (Not Including Serious) Adverse Events
    Sym023 0.03 mg/kgSym023 0.1 mg/kgSym023 0.3 mg/kgSym023 1.0 mg/kgSym023 3.0 mg/kgSym023 10.0 mg/kgSym023 20.0 mg/kg
    Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total1/1 (100%) 1/1 (100%) 3/3 (100%) 3/3 (100%) 3/3 (100%) 7/7 (100%) 5/6 (83.3%)
    Blood and lymphatic system disorders
    Anemia0/1 (0%) 00/1 (0%) 01/3 (33.3%) 10/3 (0%) 01/3 (33.3%) 11/7 (14.3%) 12/6 (33.3%) 3
    Gastrointestinal disorders
    Constipation0/1 (0%) 00/1 (0%) 00/3 (0%) 01/3 (33.3%) 10/3 (0%) 01/7 (14.3%) 11/6 (16.7%) 1
    Nausea0/1 (0%) 00/1 (0%) 01/3 (33.3%) 10/3 (0%) 01/3 (33.3%) 10/7 (0%) 01/6 (16.7%) 2
    Diarrhoea0/1 (0%) 00/1 (0%) 00/3 (0%) 00/3 (0%) 00/3 (0%) 02/7 (28.6%) 20/6 (0%) 0
    Pyrexia0/1 (0%) 00/1 (0%) 00/3 (0%) 00/3 (0%) 01/3 (33.3%) 11/7 (14.3%) 10/6 (0%) 0
    General disorders
    Fatigue1/1 (100%) 11/1 (100%) 42/3 (66.7%) 31/3 (33.3%) 11/3 (33.3%) 22/7 (28.6%) 21/6 (16.7%) 1
    Hepatobiliary disorders
    Hyperbilirubinemia0/1 (0%) 00/1 (0%) 01/3 (33.3%) 31/3 (33.3%) 10/3 (0%) 00/7 (0%) 00/6 (0%) 0
    Infections and infestations
    Urinary tract infection0/1 (0%) 00/1 (0%) 00/3 (0%) 01/3 (33.3%) 11/3 (33.3%) 10/7 (0%) 01/6 (16.7%) 1
    Pneumonia0/1 (0%) 00/1 (0%) 01/3 (33.3%) 10/3 (0%) 00/3 (0%) 01/7 (14.3%) 10/6 (0%) 0
    Investigations
    Lipase increased0/1 (0%) 00/1 (0%) 00/3 (0%) 00/3 (0%) 00/3 (0%) 01/7 (14.3%) 20/6 (0%) 0
    Lymphocyte count decreased1/1 (100%) 30/1 (0%) 00/3 (0%) 00/3 (0%) 00/3 (0%) 01/7 (14.3%) 10/6 (0%) 0
    Metabolism and nutrition disorders
    Hypophosphatemia0/1 (0%) 00/1 (0%) 01/3 (33.3%) 21/3 (33.3%) 30/3 (0%) 01/7 (14.3%) 11/6 (16.7%) 1
    Decreased appetite0/1 (0%) 00/1 (0%) 00/3 (0%) 00/3 (0%) 00/3 (0%) 01/7 (14.3%) 11/6 (16.7%) 1
    Hyponatremia0/1 (0%) 00/1 (0%) 00/3 (0%) 00/3 (0%) 01/3 (33.3%) 10/7 (0%) 01/6 (16.7%) 1
    Musculoskeletal and connective tissue disorders
    Back pain0/1 (0%) 00/1 (0%) 00/3 (0%) 01/3 (33.3%) 10/3 (0%) 00/7 (0%) 01/6 (16.7%) 1
    Pain in extremity0/1 (0%) 00/1 (0%) 00/3 (0%) 00/3 (0%) 00/3 (0%) 01/7 (14.3%) 11/6 (16.7%) 1
    Psychiatric disorders
    Anxiety0/1 (0%) 00/1 (0%) 00/3 (0%) 00/3 (0%) 00/3 (0%) 00/7 (0%) 02/6 (33.3%) 2
    Respiratory, thoracic and mediastinal disorders
    Cough0/1 (0%) 00/1 (0%) 01/3 (33.3%) 20/3 (0%) 01/3 (33.3%) 12/7 (28.6%) 20/6 (0%) 0
    Vascular disorders
    Hypertension0/1 (0%) 00/1 (0%) 00/3 (0%) 01/3 (33.3%) 10/3 (0%) 02/7 (28.6%) 20/6 (0%) 0

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/TitleMedical Director
    OrganizationSymphogen AS
    Phone0045 45265050
    Emailinfo@symphogen.com
    Responsible Party:
    Symphogen A/S
    ClinicalTrials.gov Identifier:
    NCT03489343
    Other Study ID Numbers:
    • Sym023-01
    First Posted:
    Apr 5, 2018
    Last Update Posted:
    Oct 12, 2021
    Last Verified:
    Aug 1, 2021