Safety and Efficacy of MAK683 in Adult Patients With Advanced Malignancies

Diffuse Large B-cell Lymphoma Clinical Trial

Official title:

A Phase I/II, Multicenter, Open-label Study of MAK683 in Adult Patients With Advanced Malignancies

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02900651
• Other study ID #: CMAK683X2101
• Secondary ID: 2016-001860-12
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: October 3, 2016
• Est. completion date: July 26, 2024

Study information

• Verified date: April 2024
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 139
• Est. completion date: July 26, 2024
• Est. primary completion date: July 26, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Diffuse Large B-cell Lymphoma
• Lymphoma, Large B-Cell, Diffuse

Intervention

Drug:
• MAK683
Drug: MAK683

Locations

Country	Name	City	State
Canada	Novartis Investigative Site	Toronto	Ontario
China	Novartis Investigative Site	Chengdu	Sichuan
China	Novartis Investigative Site	Shanghai
France	Novartis Investigative Site	Villejuif
Germany	Novartis Investigative Site	Freiburg
Germany	Novartis Investigative Site	Koeln
Hong Kong	Novartis Investigative Site	Hong Kong
Italy	Novartis Investigative Site	Milano	MI
Italy	Novartis Investigative Site	Rozzano	MI
Japan	Novartis Investigative Site	Fukuoka-city	Fukuoka
Japan	Novartis Investigative Site	Sunto Gun	Shizuoka
Singapore	Novartis Investigative Site	Singapore
Spain	Novartis Investigative Site	Madrid
United States	Uni of TX MD Anderson Cancer Cntr Dept of Onc	Houston	Texas
United States	UCSF .	San Francisco	California
United States	UCLA Santa Monica Hem Onco	Santa Monica	California

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Canada,  China,  France,  Germany,  Hong Kong,  Italy,  Japan,  Singapore,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of dose limiting toxicities (DLTs)	Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs)	up to 28 days
Primary	Safety and tolerability	Incidence and severity of AEs, SAEs, changes in laboratory values, vital signs and ECGs, dose interruptions and reductions	up to approximately 3 years
Secondary	Overall Response Rate (ORR)		up to 30 months
Secondary	Duration of overall response (DOR)		up to 30 months
Secondary	Progression-free survival (PFS)		up to 30 months
Secondary	Best Overall Response (BOR)		up to 30 months
Secondary	Peak Plasma Concentration (Cmax) of MAK683	Pharmacokinetic profile of MAK683	30 months
Secondary	Area Under the Plasma Concentration (AUC) Time Curve of MAK683	Pharmacokinetic profile of MAK683	30 months
Secondary	Half-Life of MAK683	Pharmacokinetic profile of MAK683	30 months
Secondary	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	up to day 15