The purpose of this Phase I/II study is to establish the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) and to evaluate the safety, antitumor activity and pharmacokinetic (PK) profile of MAK683 in patients with advanced malignancies such as Diffuse Large B cell Lymphoma (DLBCL), nasopharyngeal carcinoma (NPC) or other advanced solid tumors for whom no further effective standard treatment is available.
The purpose phase I of this trial is to characterize safety and tolerability and determine the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of MAK683. The purpose of the phase II of this trial is to evaluate the anti-tumor activity of MAK683. Phase II part will not be opened.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
139
Drug: MAK683
UCSF .
San Francisco, California, United States
UCLA Santa Monica Hematology Oncology
Santa Monica, California, United States
Uni Of TX MD Anderson Cancer Cntr Dept of Onc
Incidence of dose limiting toxicities (DLTs)
Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: up to 28 days
Safety and tolerability
Incidence and severity of AEs, SAEs, changes in laboratory values, vital signs and ECGs, dose interruptions and reductions
Time frame: up to approximately 3 years
Overall Response Rate (ORR)
Time frame: up to 30 months
Duration of overall response (DOR)
Time frame: up to 30 months
Progression-free survival (PFS)
Time frame: up to 30 months
Best Overall Response (BOR)
Time frame: up to 30 months
Peak Plasma Concentration (Cmax) of MAK683
Pharmacokinetic profile of MAK683
Time frame: 30 months
Area Under the Plasma Concentration (AUC) Time Curve of MAK683
Pharmacokinetic profile of MAK683
Time frame: 30 months
Half-Life of MAK683
Pharmacokinetic profile of MAK683
Time frame: 30 months
H3K27 tri methylation level in PBMC
Cycle 1 Day 1,8,15 Cycle 2 Day1 Cycle 3 Day 1 End of treatment (EOT); Disease progression PBMC: peripheral blood mononuclear cell
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Houston, Texas, United States
Novartis Investigative Site
Toronto, Ontario, Canada
Novartis Investigative Site
Chengdu, Sichuan, China
Novartis Investigative Site
Shanghai, China
Novartis Investigative Site
Villejuif, France
Novartis Investigative Site
Cologne, Germany
Novartis Investigative Site
Freiburg im Breisgau, Germany
Novartis Investigative Site
Hong Kong, Hong Kong
...and 6 more locations
Time frame: up to day 15