Diffuse Large B-cell Lymphoma
Conditions
Keywords
MAK683, DLBCL, EED - Embryonic ectoderm development, EZH2 - Enhancer of zeste homolog 2
Brief summary
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.
Detailed description
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.
Interventions
DRUGMAK683
Drug: MAK683
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Eastern Cooperative Oncology Group (ECOG): 0 to 2 2. Relapsed or refractory diffuse large B cell lymphoma with measurable disease as determined by Non-Hodgkin's Lymphoma Cheson response criteria (2014) 3. Advanced or recurrent/metastatic solid tumor, including nasopharyngeal carcinoma, castration-resistant prostate cancer, gastric cancer, ovarian clear cell carcinoma and sarcoma, with measurable disease as determined by RECIST 1.1.
Exclusion criteria
1. Other malignant diseases than the ones 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 central nervous system (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 ≤ 50,000/mm3 * Hemoglobin (Hgb) ≤ 80 g/L * Absolute neutrophil count (ANC) ≤ 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 \>1.5 x ULN * Serum creatinine \> 1.5 x ULN and/or creatinine clearance ≤ 50 mL/min
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of dose limiting toxicities (DLTs) | up to 28 days | Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) |
| Safety and tolerability | up to approximately 3 years | Incidence and severity of AEs, SAEs, changes in laboratory values, vital signs and ECGs, dose interruptions and reductions |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free survival (PFS) | up to 30 months | — |
| Best Overall Response (BOR) | up to 30 months | — |
| Peak Plasma Concentration (Cmax) of MAK683 | 30 months | Pharmacokinetic profile of MAK683 |
| Overall Response Rate (ORR) | up to 30 months | — |
| Half-Life of MAK683 | 30 months | Pharmacokinetic profile of MAK683 |
| H3K27 tri methylation level in PBMC | up to day 15 | Cycle 1 Day 1,8,15 Cycle 2 Day1 Cycle 3 Day 1 End of treatment (EOT); Disease progression PBMC: peripheral blood mononuclear cell |
| Area Under the Plasma Concentration (AUC) Time Curve of MAK683 | 30 months | Pharmacokinetic profile of MAK683 |
| Duration of overall response (DOR) | up to 30 months | — |
Countries
Canada, China, France, Germany, Hong Kong, Italy, Japan, Singapore, Spain, United States
Outcome results
None listed