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

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ClinicalTrials.gov Identifier: NCT02460224
Recruitment Status : Recruiting
First Posted : June 2, 2015
Last Update Posted : December 18, 2017
Sponsor:
Information provided by (Responsible Party):

Study Description
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.

Condition or disease Intervention/treatment Phase
Advanced Solid Tumors Drug: LAG525 Drug: PDR001 Phase 1 Phase 2

Study Design

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 515 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : June 17, 2015
Estimated Primary Completion Date : April 28, 2019
Estimated Study Completion Date : April 28, 2019

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
Experimental: Arm A
Single agent treatment arm with LAG525
Drug: LAG525
study drug 1
Experimental: Arm B: combination of LAG525 and PDR001
Combination treatment arm with LAG525 and PDR001
Drug: LAG525
study drug 1
Drug: PDR001
study drug 2
Experimental: Arm C
Single agent treatment arm with LAG525 in Japanese pts
Drug: LAG525
study drug 1


Outcome Measures

Primary Outcome Measures :
  1. 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

  2. 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.


Secondary Outcome Measures :
  1. AUC [ Time Frame: 30 months ]
    Characterize the pharmacokinetic profile of single agent LAG525 given alone and in combination with PDR001

  2. 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

  3. 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

  4. 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

  5. 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

  6. Safety incidence of Adverse Events (AEs [ Time Frame: 30 months ]
    Characterize the safety of single agent LAG525 given alone and in combination with PDR001

  7. Tolerability measured by dose interruptions [ Time Frame: 30 months ]
    Characterize the tolerability of single agent LAG525 given alone and in combination with PDR001

  8. 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

  9. 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

  10. 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

  11. 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

  12. Cmax [ Time Frame: 30 months ]
    Characterize the pharmacokinetic profile of single agent LAG525 given alone and in combination with PDR001

  13. Tmax [ Time Frame: 30 months ]
    Characterize the pharmacokinetic profile of single agent LAG525 given alone and in combination with PDR001

  14. half-life [ Time Frame: 30 months ]
    Characterize the pharmacokinetic profile of single agent LAG525 given alone and in combination with PDR001

  15. Tolerability measured by dose reductions [ Time Frame: 30 months ]
    Characterize the tolerability of single agent LAG525 given alone and in combination with PDR001


Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
Contacts and Locations

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): NCT02460224


Contacts
Contact: Novartis Pharmaceuticals 1-888-669-6682 Novartis.email@novartis.com
Contact: Novartis Pharmaceuticals +41613241111

  Show 22 Study Locations
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
More Information

Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02460224     History of Changes
Other Study ID Numbers: CLAG525X2101C
First Posted: June 2, 2015    Key Record Dates
Last Update Posted: December 18, 2017
Last Verified: December 2017
Individual Participant Data (IPD) Sharing Statement:
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


Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Novartis ( Novartis Pharmaceuticals ):
Non-small cell lung cancer
Melanoma
Renal cancer
Mesothelioma
Triple Negative Breast
TNBC
Renal