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

Primary Outcome Measures

• 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.

Secondary Outcome Measures

• 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

Eligibility

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.

https://clinicaltrials.gov/ct2/show/study/NCT02460224?cond=Mesothelioma&draw=3&rank=316#contacts

History of drug-induced pneumonitis or current pneumonitis.