Clinical Trials /

Safety and Efficacy of LAG525 Single Agent and in Combination With PDR001 in Patients With Advanced Malignancies.

NCT02460224

Description:

This study is to characterize the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and anti-tumor activity of LAG525 as a single agent and in combination with PDR001 to adult patients with solid tumors. The study consists of a dose escalation phase (I) to determine the maximum tolerated dose (MTD) or recommended Phase 2 dose (RP2D) for LAG525 as a single agent and in combination with PDR001, and a dose expansion phase (II) which will characterize treatment of LAG525 as a single agent and in combination with PDR001 at the MTD or RP2D.

Related Conditions:
  • Breast Carcinoma
  • Malignant Solid Tumor
Recruiting Status:

Active, not recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Safety and Efficacy of LAG525 Single Agent and in Combination With PDR001 in Patients With Advanced Malignancies.
  • Official Title: A Phase I/II, Open Label, Multicenter Study of the Safety and Efficacy of LAG525 Single Agent and in Combination With PDR001 Administered to Patients With Advanced Malignancies

Clinical Trial IDs

  • ORG STUDY ID: CLAG525X2101C
  • NCT ID: NCT02460224

Conditions

  • Advanced Solid Tumors

Interventions

DrugSynonymsArms
LAG525Arm A
PDR001Arm B: combination of LAG525 and PDR001

Purpose

This study is to characterize the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and anti-tumor activity of LAG525 as a single agent and in combination with PDR001 to adult patients with solid tumors. The study consists of a dose escalation phase (I) to determine the maximum tolerated dose (MTD) or recommended Phase 2 dose (RP2D) for LAG525 as a single agent and in combination with PDR001, and a dose expansion phase (II) which will characterize treatment of LAG525 as a single agent and in combination with PDR001 at the MTD or RP2D.

Trial Arms

NameTypeDescriptionInterventions
Arm AExperimentalSingle agent treatment arm with LAG525
  • LAG525
Arm B: combination of LAG525 and PDR001ExperimentalCombination treatment arm with LAG525 and PDR001
  • LAG525
  • PDR001
Arm CExperimentalSingle agent treatment arm with LAG525 in Japanese pts
  • LAG525

Eligibility Criteria

        Inclusion Criteria:

        Phase I part:

        - Patients with advanced/metastatic solid tumors, with measurable or non-measurable disease
        as determined by RECIST version 1.1 (refer to Appendix 1), who have progressed despite
        standard therapy or are intolerant of standard therapy, or for whom no standard therapy
        exists

        Phase II part:

          -  Patients with advanced/metastatic solid tumors, with at least one measurable lesion as
             determined by RECIST version 1.1, who have had disease progression following their
             last prior therapy and fit into one of the following groups:

          -  Group 1: NSCLC

          -  Group 2: Melanoma

          -  Group 3: Renal cancer

          -  Group 4: Mesothelioma

          -  Group 5: TNBC

          -  Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 1

          -  Patient must have a site of disease amenable to biopsy, and be a candidate for tumor
             biopsy.

        Exclusion Criteria:

          -  History of severe hypersensitivity reactions to study treatment ingredients or other
             mAbs

          -  Active, known or suspected autoimmune disease

          -  Active infection requiring systemic antibiotic therapy

          -  HIV infection. Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection

          -  Patients receiving chronic treatment with systemic steroid therapy, other than
             replacement-dose corticosteroids in the setting of adrenal insufficiency

          -  Patients receiving systemic treatment with any immunosuppressive medication

          -  Use of live vaccines against infectious disease within 4 weeks of initiation of study
             treatment

          -  Systemic anti-cancer therapy within 2 weeks of the first dose of study treatment.

          -  Presence of symptomatic central nervous system (CNS) metastases or CNS metastases that
             require local CNS-directed therapy or increasing doses of corticosteroids within the
             prior 2 weeks

          -  History of drug-induced pneumonitis or current pneumonitis.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Phase I part: Incidence of dose limiting toxicities (DLTs)
Time Frame:30 months
Safety Issue:
Description:A dose-limiting toxicity (DLT) is defined as an adverse event or abnormal laboratory value assessed as having a suspected relationship to study drug, and unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurs within the first cycle of treatment with single agent LAG525 or within the first two cycles of treatment with the combination of LAG525 and PDR001

Secondary Outcome Measures

Measure:AUC
Time Frame:30 months
Safety Issue:
Description:Characterize the pharmacokinetic profile of single agent LAG525 given alone and in combination with PDR001
Measure:Presence and/ or concentration of anti-LAG525 and anti-PDR001 antibodies
Time Frame:30 months
Safety Issue:
Description:Assess emergence of anti-LAG525, and anti-PDR001 antibodies following one or more intravenous (i.v.) infusions of single agent LAG525 given alone or in combination with PDR001
Measure:Correlation of PD-L1, Lymphocyte activation gene-3 LAG-3 expression
Time Frame:30 months
Safety Issue:
Description:Assess potential predictors of efficacy of single agent LAG525 and the combination of LAG525 and PDR001
Measure:Overall response Rate (ORR)
Time Frame:30 months
Safety Issue:
Description:Evaluate the preliminary antitumor activity per RECIST as well as per immune related Response Criteria (irRC) on single agent LAG525 given alone or in combination with PDR001
Measure:Expression of IFN-γ immune-related genes by mRNA profiling
Time Frame:30 months
Safety Issue:
Description:Assess the pharmacodynamic effect of single agent LAG525 and the combination of LAG525 and PDR001
Measure:Safety incidence of Adverse Events (AEs
Time Frame:30 months
Safety Issue:
Description:Characterize the safety of single agent LAG525 given alone and in combination with PDR001
Measure:Tolerability measured by dose interruptions
Time Frame:30 months
Safety Issue:
Description:Characterize the tolerability of single agent LAG525 given alone and in combination with PDR001
Measure:Progression free survival (PFS)
Time Frame:30 months
Safety Issue:
Description:Evaluate the preliminary antitumor activity per RECIST as well as per immune related Response Criteria (irRC) on single agent LAG525 given alone or in combination with PDR001
Measure:Duration of response (DOR)
Time Frame:30 months
Safety Issue:
Description:Evaluate the preliminary antitumor activity per RECIST as well as per immune related Response Criteria (irRC) on single agent LAG525 given alone or in combination with PDR001
Measure:Disease control rate (DCR)
Time Frame:30 months
Safety Issue:
Description:Evaluate the preliminary antitumor activity per RECIST as well as per immune related Response Criteria (irRC) on single agent LAG525 given alone or in combination of PDR001
Measure:Safety measuresd by incidence of Serious Adverse Events (SAEs)
Time Frame:30 months
Safety Issue:
Description:Characterize the safety of single agent LAG525 given alone and in combination with PDR001
Measure:Cmax
Time Frame:30 months
Safety Issue:
Description:Characterize the pharmacokinetic profile of single agent LAG525 given alone and in combination with PDR001
Measure:Tmax
Time Frame:30 months
Safety Issue:
Description:Characterize the pharmacokinetic profile of single agent LAG525 given alone and in combination with PDR001
Measure:half-life
Time Frame:30 months
Safety Issue:
Description:Characterize the pharmacokinetic profile of single agent LAG525 given alone and in combination with PDR001
Measure:Tolerability measured by dose reductions
Time Frame:30 months
Safety Issue:
Description:Characterize the tolerability of single agent LAG525 given alone and in combination with PDR001

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Novartis Pharmaceuticals

Trial Keywords

  • Non-small cell lung cancer
  • Melanoma
  • Renal cancer
  • Mesothelioma
  • Triple Negative Breast
  • TNBC
  • Renal

Last Updated

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