Advanced malignancies MedDRA version: 21.1 Level: LLT Classification code 10065252 Term: Solid tumor System Organ Class: 100000004864 MedDRA version: 21.1 Level: LLT Classification code 10066481 Term: Hematological malignancy System Organ Class: 100000004864
Conditions
Sponsors
Novartis Pharma Services AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Patients Age = 18 years 2.ECOG performance status 0 to 2 3.Patients have progressed after standard therapy or are intolerant of standard therapy and for whom no standard therapy exists. 4. Measurable disease according to RECIST v1.1 for patients with solid tumors or Cheson criteria for patients with NHL (Cheson et al 2014). 5. Tumor biopsy is mandatory at study entry. Patients must have a site of disease amenable for biopsy and be a candidate for umor biopsy. On-Treatment biopsy is required for patients with solid tumors, unless determined by the Investigator as not clinically feasible. 6. Histologically or cytologically confirmed diagnosis is required for all indications - For patients with DLBCL and FL: In Phase II, patients are required to have documentation of EZH2 mutational status. Patients with relapsed or refractory indolent lymphomas, such as FL, must have signs or symptoms indicating the necessity of therapy such as described in practice guidelines ( e.g. Groupe d'Etude des Lymphomes Folliculaires (GELF) criteria, The British National Lymphoma Investigation (BNLI), Italian Society of Hematology (SIE) guideline, or others local practice guidelines). 7. For patients with NPC: Patients must have documentation of presence of p16/CDKN2A gene (at least one copy of p16/CDKN2A gene) 8. For patients with ovarian cancer: Patients must have primary tumor with great than 50% clear cell histomorphology. 9. For patients with prostate cancer: Patients must have evidence of castration resistance as evidenced by a confirmed rising PSA (per Prostate Cancer Working Group 2 [PCWG2] criteria) and a castrate^serum testosterone level (i.e. = 50 ng/dL). 10. For patients with sarcoma: Enrollment is limited to epithelioid sarcoma, other types of sarcoma with SWI/SNF alterations may be considered with approval from Novartis. 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 110 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 50
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 = 50 x 109/L (50,000/mm3) •Hemoglobin (Hgb) = 90 g/L (9 g/dL) •Absolute neutrophil count (ANC) = 1.0 x 109/L (1000/mm3) 2)Insufficient hepatic and renal function at screening: •ALP, ALT, and AST > 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 trimethylation in blood 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 expression of H3K27 trimethylation in blood ;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 ContactMedizinischer Infoservice (MCC)
Novartis Pharma GmbH
Outcome results
None listed