Advanced malignancies MedDRA version: 19.1 Level: LLT Classification code 10065252 Term: Solid tumor System Organ Class: 100000004864 MedDRA version: 19.1 Level: LLT Classification code 10066481 Term: Hematological malignancy System Organ Class: 100000004864
Conditions
Sponsors
Novartis Farmacéutica, S.A.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Patients Age > = 18 years [For Japan only: written consent is necessary from both the patient and his /her legal representative if he/she is under the age of 20 years.] 2.ECOG performance status 0 to 2 3.Patients with relapsed or refractory diffuse large B cell lymphoma, follicular lymphoma, other B cell lymphoma with measurable disease as determined by Non-Hodgkin’s Lymphoma Cheson response criteria (2014) 4.Patients with advanced solid tumor, including Nasopharyngeal carcinoma (Phase II part- Nasopharyngeal carcinoma patients without homozygous p16-deletion and other indications supported by emerging data, with measurable disease as determined by RECIST 1.1. Other protocol-defined inclusion criteria may apply 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 100 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 48
Exclusion criteria
Exclusion criteria: 1.Other malignant disease than the one being treated in this study 2.Severe and/or uncontrolled medical conditions that in the investigator’s opinion could affect the safety of individual or impair the assessment of study result. 3.B-cell lymphoma patients who have received prior allogeneic stem cell transplant 4.Patient have received anti-cancer therapies within defined time frames prior to the first dose of study treatment 5.Symptomatic CNS involvement which are neurologically unstable or requiring increasing doses of steroids to control. 6.Patient having out of range laboratory values defined as: 1)Insufficient bone marrow function at screening: •Platelets 3 x ULN (>5 x ULN if subject has liver metastases) •Total bilirubin > =2 x ULN •Serum creatinine > 1.5 x ULN and/or creatinine clearance < = 50 mL/min 7.Unable to stop any prohibited medications, including strong CYP3A4 inhibitors or inducers, CYP3A4 or CYP2C8 substrates with a narrow therapeutic index, long acting proton pump inhibitors. Other protocol-defined exclusion criteria may apply.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Phase I: To characterize safety and tolerability and determine the MTD and/or RP2D of MAK683 Phase II: To assess the anti-tumor activity of MAK683;Secondary Objective: Phase I: •To characterize the anti-tumor activity of MAK683 •To characterize the PK profile of MAK683 •To characterize the pharmacodynamics effect of MAK683 Phase II: •To characterize the anti-tumor activity of MAK683 •To characterize the safety and tolerability of MAK683 •To characterize the PK profile of MAK683 •To characterize the pharmacodynamics effect of MAK683;Primary end point(s): Phase I: Safety: 1.Incidence of dose limiting toxicities (DLTs) in the first 28 days of treatment 2.Incidence and severity of AEs and SAEs, including changes in laboratory parameters, vital signs and ECGs Tolerability: Dose interruptions, reductions and dose intensity Phase II: Overall response rate (ORR), based on local assessment per Response Assessment of Hodgkin and Non-Hodgkin Lymphoma (Cheson, 2014), Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and PCWG2;Timepoint(s) of evaluation of this end point: Phase I: Safety: 1. Day 28 2. End of study Phase II: End of study | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Phase I part: ORR, Duration of overall response (DOR), Progression-free survival (PFS) and Best Overall Response (BOR) Plasma concentrations and derived PK parameters of MAK683 Pre-and post-treatment expression of H3K27 tri methylation in PBMC Phase II part: Duration of overall response (DOR), Progression-free survival (PFS) and Best Overall Response (BOR) Safety: Incidence and severity of AEs and SAEs, including changes in laboratory parameters, vital signs and ECGs Tolerability: Dose interruptions, reductions and dose intensity. Plasma concentrations and PK profiles of MAK683 Pre-and post-treatment level of H3K27 tri methylation in PBMC;Timepoint(s) of evaluation of this end point: End of study | — |
Countries
Canada, China, France, Germany, Hong Kong, Italy, Japan, Korea, Republic of, Netherlands, Singapore, Spain, United States
Contacts
Public ContactDepartamento Médico Oncología (GMO)
Novartis Farmacéutica, S.A.
Outcome results
None listed