Clinical Trials /

Sym021 Monotherapy and in Combination With Sym022 or Sym023 in Patients With Advanced Solid Tumor Malignancies or Lymphomas

NCT03311412

Description:

The primary purpose of this study is to see if Sym021 is safe and tolerable as monotherapy and in combination with either Sym022 or Sym023 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.

Related Conditions:
  • Lymphoma
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Sym021 Monotherapy and in Combination With Sym022 or Sym023 in Patients With Advanced Solid Tumor Malignancies or Lymphomas
  • Official Title: A Phase 1, Open-Label, Multicenter Trial Investigating the Safety, Tolerability, and Preliminary Antineoplastic Activity of Sym021 (Anti-PD-1) as Monotherapy and in Combination With Either Sym022 (Anti-LAG-3) or Sym023 (Anti-TIM-3) in Patients With Advanced Solid Tumor Malignancies or Lymphomas

Clinical Trial IDs

  • ORG STUDY ID: Sym021-01
  • NCT ID: NCT03311412

Conditions

  • Metastatic Cancer
  • Solid Tumor
  • Lymphoma

Interventions

DrugSynonymsArms
Sym021Anti-PD-1Sym021 Dose Level 1
Sym022Anti-LAG-3Arm A: Sym021+Sym022 Dose Level 1
Sym023Anti-TIM-3Arm B: Sym021+Sym023 Dose Level 1

Purpose

The primary purpose of this study is to see if Sym021 is safe and tolerable as monotherapy and in combination with either Sym022 or Sym023 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.

Detailed Description

      Part 1 of this study will evaluate the preliminary safety, tolerability, and dose-limiting
      toxicities (DLTs) of Sym021, an anti-programmed cell death protein 1 (PD-1) 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 Sym021 when administered once every 2
      weeks (Q2W) by 30-minute intravenous (IV) infusion. Sym021 will be given to patients in
      escalating dose cohorts; each patient will be given one fixed dose level.

      Part 2 of this study will evaluate the safety, tolerability, and DLTs to establish the MTD
      and/or RP2D of sequential escalating doses of Sym022 and Sym023 when administered Q2W in
      combination with the RP2D of Sym021, each by IV infusion. Dose levels of Sym021+Sym022 and
      Sym021+Sym023 will be evaluated until for each combination the MTD is identified, a maximum
      administered dose (MAD) is reached, or until a RP2D for the added mAb (Sym022 or Sym023) in
      combination with Sym021 is selected. Each patient will be given one fixed dose level of an
      assigned combination.
    

Trial Arms

NameTypeDescriptionInterventions
Sym021 Dose Level 1ExperimentalPart 1, Sym021 monotherapy dose level 1
  • Sym021
Sym021 Dose Level 2ExperimentalPart 1, Sym021 monotherapy dose level 2
  • Sym021
Sym021 Dose Level 3ExperimentalPart 1, Sym021 monotherapy dose level 3
  • Sym021
Arm A: Sym021+Sym022 Dose Level 1ExperimentalPart 2, Arm A: Sym021 RP2D in combination with dose level 1 of Sym022
  • Sym021
  • Sym022
Arm A: Sym021+Sym022 Dose Level 2ExperimentalPart 2, Arm A: Sym021 RP2D in combination with dose level 2 of Sym022
  • Sym021
  • Sym022
Arm A: Sym021+Sym022 Dose Level 3ExperimentalPart 2, Arm A: Sym021 RP2D in combination with dose level 3 of Sym022
  • Sym021
  • Sym022
Arm A: Sym021+Sym022 Dose Level 4ExperimentalPart 2, Arm A: Sym021 RP2D in combination with dose level 4 of Sym022
  • Sym021
  • Sym022
Arm B: Sym021+Sym023 Dose Level 1ExperimentalPart 2, Arm B: Sym021 RP2D in combination with dose level 1 of Sym023
  • Sym021
  • Sym023
Arm B: Sym021+Sym023 Dose Level 2ExperimentalPart 2, Arm B: Sym021 RP2D in combination with dose level 2 of Sym023
  • Sym021
  • Sym023
Arm B: Sym021+Sym023 Dose Level 3ExperimentalPart 2, Arm B: Sym021 RP2D in combination with dose level 3 of Sym023
  • Sym021
  • Sym023
Arm B: Sym021+Sym023 Dose Level 4ExperimentalPart 2, Arm B: Sym021 RP2D in combination with dose level 4 of Sym023
  • Sym021
  • Sym023
Arm B: Sym021+Sym023 Dose Level 5ExperimentalPart 2, Arm B: Sym021 RP2D in combination with dose level 5 of Sym023
  • Sym021
  • Sym023
Arm B: Sym021+Sym023 Dose Level 6ExperimentalPart 2, Arm B: Sym021 RP2D in combination with dose level 6 of Sym023
  • Sym021
  • Sym023
Arm B: Sym021+Sym023 Dose Level 7ExperimentalPart 2, Arm B: Sym021 RP2D in combination with dose level 7 of Sym023
  • Sym021
  • Sym023

Eligibility 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 lymphoma.

          -  Malignancy (solid tumor or lymphoma) that is currently not amenable to surgical
             intervention due to either medical contraindications or non-resectability 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.

          -  Persons of childbearing potential agreeing 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(s); men agreeing to
             refrain from sperm donation during this period.

        Exclusion Criteria:

          -  Women who are pregnant or intending to become pregnant before, during, or within 6
             months after the last dose of study drug; women who are breastfeeding; persons of
             childbearing potential and not willing to use a highly effective method of
             contraception.

          -  Central nervous system (CNS) malignancies; patients with known, untreated 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 lymphoma.

          -  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 an 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 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 except for persistent Grade 2 alopecia, peripheral neuropathy, decreased
             hemoglobin, lymphopenia, hypomagnesemia, and/or end-organ failure being adequately
             managed by hormone replacement 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).

        Drugs and Other Treatments Exclusion Criteria:

          -  Part 2 Combination Dose-Escalations ONLY: Prior therapy with:

               -  Sym021 or other inhibitors of PD-1/PD-L1.

               -  Sym022 or other inhibitors of LAG-3, if participating in Arm A.

               -  Sym023 or other inhibitors of TIM-3, if participating in Arm B.

          -  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 study drug administration and during study, with exceptions.

          -  Any other investigational treatments within 2 weeks prior to and during study;
             includes participation in any medical device or supportive care therapeutic
             intervention trials.

          -  Radiotherapy, with exceptions.

          -  Use of live vaccines against infectious diseases 4 weeks prior to first study drug
             administration and during study.

          -  Immunosuppressive or systemic hormonal therapy within 2 weeks prior to first study
             drug administration and during study, with exceptions.

          -  Prophylactic use of hematopoietic growth factors within 1 week prior to first study
             drug administration and during Cycle 1 of study.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Part 1: Assessment of treatment emergent adverse events (AEs) meeting DLT criteria.
Time Frame:12 months
Safety Issue:
Description:Assess the safety and tolerability of Sym021 monotherapy on a Q2W schedule. Assessment based on the occurrence of AEs meeting DLT criteria measured during Cycle 1.

Secondary Outcome Measures

Measure:Evaluation of the immunogenicity of Sym021 as a single agent and in combination with Sym022 and Sym023.
Time Frame:24 months
Safety Issue:
Description:Serum sampling to assess the potential for anti-drug antibody (ADA) formation.
Measure:Evaluation of objective response (OR) or stable disease (SD).
Time Frame:24 months
Safety Issue:
Description: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.
Measure:Time to progression (TTP) of disease.
Time Frame:24 months
Safety Issue:
Description: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.
Measure:Area under the concentration-time curve in a dosing interval (AUC)
Time Frame:24 months
Safety Issue:
Description:Will be estimated using non-compartmental methods and actual timepoints.
Measure:Maximum concentration (Cmax)
Time Frame:24 months
Safety Issue:
Description:Will be derived from observed data.
Measure:Time to reach maximum concentration (Tmax)
Time Frame:24 months
Safety Issue:
Description:Will be derived from observed data.
Measure:Trough concentration (Ctrough)
Time Frame:24 months
Safety Issue:
Description:Will be derived from observed data.
Measure:Terminal elimination half-life (T½)
Time Frame:24 months
Safety Issue:
Description:Will be estimated using non-compartmental methods and actual timepoints.
Measure:Clearance (CL)
Time Frame:24 months
Safety Issue:
Description:Will be estimated using non-compartmental methods and actual timepoints.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Symphogen A/S

Trial Keywords

  • Locally advanced/unresectable
  • Metastatic solid tumor
  • Lymphoma
  • Anti-PD-1
  • PD-1
  • PD1
  • Anti-LAG-3
  • LAG-3
  • LAG3
  • Anti-TIM-3
  • TIM-3
  • TIM3

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