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

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: NCT02460224
Recruitment Status : Active, not recruiting
First Posted : June 2, 2015
Last Update Posted : September 9, 2020
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Tracking Information
First Submitted Date  ICMJE May 9, 2015
First Posted Date  ICMJE June 2, 2015
Last Update Posted Date September 9, 2020
Actual Study Start Date  ICMJE June 17, 2015
Estimated Primary Completion Date November 23, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 29, 2015)
  • Phase I part: Incidence of dose limiting toxicities (DLTs) [ Time Frame: 30 months ]
    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
  • Phase II part: Overall response Rate per RECIST V1.1 [ Time Frame: 30 months ]
    Overall Response Rate (ORR) is defined as the proportion of patients with a best overall response of complete response (CR) or partial response (PR) based on local Investigator assessment, as defined in RECIST v1.1. Estimation of the true ORR in this part of the study will be based upon the observed ORR for patients in full analysis set.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 15, 2017)
  • AUC [ Time Frame: 30 months ]
    Characterize the pharmacokinetic profile of single agent LAG525 given alone and in combination with PDR001
  • Presence and/ or concentration of anti-LAG525 and anti-PDR001 antibodies [ Time Frame: 30 months ]
    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
  • Correlation of PD-L1, Lymphocyte activation gene-3 LAG-3 expression [ Time Frame: 30 months ]
    Assess potential predictors of efficacy of single agent LAG525 and the combination of LAG525 and PDR001
  • Overall response Rate (ORR) [ Time Frame: 30 months ]
    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
  • Expression of IFN-γ immune-related genes by mRNA profiling [ Time Frame: 30 months ]
    Assess the pharmacodynamic effect of single agent LAG525 and the combination of LAG525 and PDR001
  • Safety incidence of Adverse Events (AEs [ Time Frame: 30 months ]
    Characterize the safety of single agent LAG525 given alone and in combination with PDR001
  • Tolerability measured by dose interruptions [ Time Frame: 30 months ]
    Characterize the tolerability of single agent LAG525 given alone and in combination with PDR001
  • Progression free survival (PFS) [ Time Frame: 30 months ]
    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
  • Duration of response (DOR) [ Time Frame: 30 months ]
    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
  • Disease control rate (DCR) [ Time Frame: 30 months ]
    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
  • Safety measuresd by incidence of Serious Adverse Events (SAEs) [ Time Frame: 30 months ]
    Characterize the safety of single agent LAG525 given alone and in combination with PDR001
  • Cmax [ Time Frame: 30 months ]
    Characterize the pharmacokinetic profile of single agent LAG525 given alone and in combination with PDR001
  • Tmax [ Time Frame: 30 months ]
    Characterize the pharmacokinetic profile of single agent LAG525 given alone and in combination with PDR001
  • half-life [ Time Frame: 30 months ]
    Characterize the pharmacokinetic profile of single agent LAG525 given alone and in combination with PDR001
  • Tolerability measured by dose reductions [ Time Frame: 30 months ]
    Characterize the tolerability of single agent LAG525 given alone and in combination with PDR001
Original Secondary Outcome Measures  ICMJE
 (submitted: May 29, 2015)
  • AUC [ Time Frame: 30 months ]
    Characterize the pharmacokinetic profile of single agent LAG525 given alone and in combination with PDR001
  • Presence and/ or concentration of anti-LAG525 and anti-PDR001 antibodies [ Time Frame: 30 months ]
    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
  • Correlation of PD-L1, Lymphocyte activation gene-3 LAG-3 expression [ Time Frame: 30 months ]
    Assess potential predictors of efficacy of single agent LAG525 and the combination of LAG525 and PDR001
  • Overall response Rate (ORR) [ Time Frame: 30 months ]
    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
  • Expression of IFN-γ immune-related genes by mRNA profiling [ Time Frame: 30 months ]
    Assess the pharmacodynamic effect of single agent LAG525 and the combination of LAG525 and PDR001
  • Safety incidence of Adverse Events (AEs [ Time Frame: 30 months ]
    Characterize the safety of single agent LAG525 given alone and in combination with PDR001
  • Tolerability measured by dose interruptions [ Time Frame: 30 months ]
    Characterize the tolerability of single agent LAG525 given alone and in combination with PDR001
  • Progression free survival (PFS) [ Time Frame: 30 months ]
    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
  • Duration of response (DOR) [ Time Frame: 30 months ]
    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
  • Disease control rate (DCR) [ Time Frame: 30 months ]
    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
  • Safety measuresd by incidence of Serious Adverse Events (SAEs) [ Time Frame: 30 months ]
    Characterize the safety of single agent LAG525 given alone and in combination with PDR001
  • Cmax [ Time Frame: 30 months ]
    Characterize the pharmacokinetic profile of single agent LAG525 given alone and in combination with PDR001
  • Tmax [ Time Frame: 30 months ]
    Characterize the pharmacokinetic profile of single agent LAG525 given alone and in combination with PDR001
  • half-life [ Time Frame: 30 months ]
    Characterize the pharmacokinetic profile of single agent LAG525 given alone and in combination with PDR001
  • Tolerability measured by dose reductions [ Time Frame: 30 months ]
    Characterize the tolerability of single agent LAG525 given alone and in combination with PDR001
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety and Efficacy of LAG525 Single Agent and in Combination With PDR001 in Patients With Advanced Malignancies.
Official Title  ICMJE 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
Brief Summary 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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Advanced Solid Tumors
Intervention  ICMJE
  • Drug: LAG525
    study drug 1
  • Drug: PDR001
    study drug 2
Study Arms  ICMJE
  • Experimental: Arm A
    Single agent treatment arm with LAG525
    Intervention: Drug: LAG525
  • Experimental: Arm B: combination of LAG525 and PDR001
    Combination treatment arm with LAG525 and PDR001
    Interventions:
    • Drug: LAG525
    • Drug: PDR001
  • Experimental: Arm C
    Single agent treatment arm with LAG525 in Japanese pts
    Intervention: Drug: LAG525
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: January 17, 2019)
490
Original Estimated Enrollment  ICMJE
 (submitted: May 29, 2015)
240
Estimated Study Completion Date  ICMJE November 23, 2020
Estimated Primary Completion Date November 23, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Belgium,   Canada,   France,   Germany,   Hong Kong,   Italy,   Japan,   Singapore,   Spain,   Taiwan,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02460224
Other Study ID Numbers  ICMJE CLAG525X2101C
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Plan Description:

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Responsible Party Novartis ( Novartis Pharmaceuticals )
Study Sponsor  ICMJE Novartis Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
PRS Account Novartis
Verification Date September 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP