Solid tumors
Conditions
Interventions
Product Code: LAG525
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: LAG525
CAS Number: LAG525
Current Sponsor code: LAG525
Other descriptive name: LAG525
Concentration
Sponsors
Novartis Farmacéutica, S.A.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Written informed consent must be obtained prior to any procedures 2. Age ? 18 years 3. 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. 4. 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. 5. ECOG Performance Status ? 2. 6. Patient must have a site of disease amenable to biopsy, and be a candidate for tumor biopsy according to the treating institution?s guidelines. Patient must be willing to undergo a new tumor biopsy at baseline, and during therapy on this study. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 180 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 60
Exclusion criteria
Exclusion criteria: 1. History of severe hypersensitivity reactions to other mAbs 2. Active autoimmune disease or a documented history of autoimmune disease within three years prior to screening. 3. Active infection requiring systemic antibiotic therapy. 4. Known history of HIV infection. 5. Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. 6. Systemic anti-cancer therapy within 2 weeks of the first dose of study treatment. For cytotoxic agents that have major delayed toxicity, e.g. mitomycin C and nitrosoureas, 4 weeks is indicated as washout period. 7. Phase II only: Prior PD1- or PD-L1-directed therapy with the exception of patients with renal cell cancer will have been previously treated with anti-PD-1 or anti-PD-L1 inhibitors. 8. Use of any live vaccines against infectious diseases within 4 weeks of initiation of study treatment. 9. Presence of ? CTCAE grade 2 toxicity (except alopecia, peripheral neuropathy and ototoxicity, which are excluded if ? CTCAE grade 3) due to prior cancer therapy. Other protocol-defined exclusion criteria may apply.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Phase I part - To estimate the RP2D or MTD for: ? Single agent LAG525 ? Combination of LAG525 and PDR001. Phase II part - To estimate the overall response rate per RECIST V1.1: ? Single agent LAG525 ? Combination of LAG525 and PDR001;Secondary Objective: Key Secondary Objectives: 1) To characterize the safety and tolerability of single agent LAG525 given alone and in combination with PDR001 2) To characterize the pharmacokinetic profile of single agent LAG525 given alone and in combination with PDR001 3) To 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 4) To evaluate the preliminary antitumor activity of single agent LAG525 given alone or in combination of PDR001 Other Secondary Objectives are defined in the protocol.;Primary end point(s): Phase I part: - The incidence of dose limiting toxicities ( DLTs) with single agent LAG525 & for the combination treatment of LAG525 and PDR001 Phase II part: Overall response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. of single agent LAG525 & the combination of LAG525 and PDR001.;Timepoint(s) of evaluation of this end point: Phase I: - the incidence of DLTs continously: during the first cycle of treatment with single agent LAG525; for the combination treatment of LAG525 and PDR001, the DLT window will be 2 cycles of the treatment. Phase II: - Every 2 Cycles ± 1 week from Cycle 3 Day 1 to Cycle 11 Day 1, then every 3 cycles until progression of disease per irRC or patient withdrawal. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. a) Safety incidence and severity if adverse events (AEs) and serious adverse events (SAEs) including changes in laboratory parameters, vital signs and ECGs; b) Tolerability: Dose interruptions, reductions and dose intensity. 2. Serum PK parameters (e.g. AUC, Cmax, Tmax, t1/2 half-life)) 3. Presence and/ or concentration of anti-LAG525 and anti-PDR001 antibodies 4. Phase I Part: ORR, progression free survival (PFS), duration of response (DOR) and disease control rate (DCR); Phase II Part: ORR per immune related Response Criteria (irRC), PFS, DOR, DCR per RECIST V1.1 and per irRC;Timepoint(s) of evaluation of this end point: 1. Assessed continuously 2. Every Cycle until Cycle 6 3. Every Cycle until Cycle 6 4. Every 2 Cycles ± 1 week from Cycle 3 Day 1 to Cycle 11 Day 1, then every 3 cycles until progression of disease per irRC or patient withdrawal. | — |
Countries
Australia, Belgium, Canada, France, Germany, Hong Kong, Italy, Japan, Korea, Republic of, Singapore, Spain, Taiwan, United States
Contacts
Public ContactDepartamento Médico Oncología (GMO)
Novartis Farmacéutica, S.A.
Outcome results
None listed