Safety and Efficacy of MAK683 in Adult Patients With Advanced Malignancies

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Diffuse Large B-cell Lymphoma
• Intervention / Treatment: Drug: MAK683

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.

• Study Type: Interventional
• Enrollment (Actual): 139
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • Novartis Investigative Site
• China
  • Shanghai, China, 200032
    • Novartis Investigative Site
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • Novartis Investigative Site
• France
  • Villejuif, France, 94800
    • Novartis Investigative Site
• Germany
  • Freiburg, Germany, 79106
    • Novartis Investigative Site
  • Koeln, Germany, 50937
    • Novartis Investigative Site
• Hong Kong
  • Hong Kong, Hong Kong
    • Novartis Investigative Site
• Italy
  • MI
    • Milano, MI, Italy, 20133
      • Novartis Investigative Site
    • Rozzano, MI, Italy, 20089
      • Novartis Investigative Site
• Japan
  • Fukuoka
    • Fukuoka-city, Fukuoka, Japan, 811-1395
      • Novartis Investigative Site
  • Shizuoka
    • Sunto Gun, Shizuoka, Japan, 411 8777
      • Novartis Investigative Site
• Singapore
  • Singapore, Singapore, 168583
    • Novartis Investigative Site
• Spain
  • Madrid, Spain, 28041
    • Novartis Investigative Site
• United States
  • California
    • San Francisco, California, United States, 94115
      • UCSF .
    • Santa Monica, California, United States, 90404
      • UCLA Santa Monica Hem Onco
  • Texas
    • Houston, Texas, United States, 77030
      • Uni of TX MD Anderson Cancer Cntr Dept of Onc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase I - All; advanced stage (relapsed/refractory or recurrent/metastatic) malignancy limited to the following malignancies; DLBCL, nasopharyngeal carcinoma, gastric cancer, ovarian cancer, prostate cancer and sarcoma.	Drug: MAK683; Drug: MAK683

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of dose limiting toxicities (DLTs)	Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs)	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	up to approximately 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate (ORR)		up to 30 months
Duration of overall response (DOR)		up to 30 months
Progression-free survival (PFS)		up to 30 months
Best Overall Response (BOR)		up to 30 months
Peak Plasma Concentration (Cmax) of MAK683	Pharmacokinetic profile of MAK683	30 months
Area Under the Plasma Concentration (AUC) Time Curve of MAK683	Pharmacokinetic profile of MAK683	30 months
Half-Life of MAK683	Pharmacokinetic profile of MAK683	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	up to day 15

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): October 3, 2016
• Primary Completion (Estimated): July 26, 2024
• Study Completion (Estimated): July 26, 2024

Study Registration Dates

• First Submitted: September 2, 2016
• First Submitted That Met QC Criteria: September 9, 2016
• First Posted (Estimated): September 14, 2016

Study Record Updates

• Last Update Posted (Actual): March 1, 2024
• Last Update Submitted That Met QC Criteria: February 29, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: MAK683, DLBCL, EED - Embryonic ectoderm development, EZH2 - Enhancer of zeste homolog 2
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse
• Other Study ID Numbers: CMAK683X2101; 2016-001860-12 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

IPD Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No