Safety and Efficacy of MAK683 in Adult Patients With Advanced Malignancies

NCT02900651 | Terminated Phase 1 FDA Drug

• 2 other identifiers: CMAK683X21012016-001860-12
• Study Type: interventional
• Target: 139
• Locations: 10 countries
• Sites: 16

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.

Conditions

Diffuse Large B-cell Lymphoma

Keywords

MAK683, DLBCL, EED - Embryonic ectoderm development, EZH2 - Enhancer of zeste homolog 2

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (8)

• 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

  30 months

Study Arms (1)

Phase I - All

EXPERIMENTAL

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

Interventions

MAK683 DRUG

Drug: MAK683

Phase I - All

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Eastern Cooperative Oncology Group (ECOG): 0 to 2
• Relapsed or refractory diffuse large B cell lymphoma with measurable disease as determined by Non-Hodgkin's Lymphoma Cheson response criteria (2014)
• 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.

You may not qualify if:

• Other malignant diseases than the ones being treated in this study
• 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.
• B-cell lymphoma patients who have received prior allogeneic stem cell transplant
• Patient have received anti-cancer therapies within defined time frames prior to the first dose of study treatment
• Symptomatic central nervous system (CNS) involvement which are neurologically unstable or requiring increasing doses of steroids to control.
• Patient having out of range laboratory values defined as:
• \) 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (16)

UCSF .

San Francisco, California, 94115, United States

Location

UCLA Santa Monica Hematology Oncology

Santa Monica, California, 90404, United States

Location

Uni Of TX MD Anderson Cancer Cntr Dept of Onc

Houston, Texas, 77030, United States

Location

Novartis Investigative Site

Toronto, Ontario, M5G 2M9, Canada

Location

Novartis Investigative Site

Chengdu, Sichuan, 610041, China

Location

Novartis Investigative Site

Shanghai, 200032, China

Location

Novartis Investigative Site

Villejuif, 94800, France

Location

Novartis Investigative Site

Cologne, 50937, Germany

Location

Novartis Investigative Site

Freiburg im Breisgau, 79106, Germany

Location

Novartis Investigative Site

Hong Kong, Hong Kong

Location

Novartis Investigative Site

Milan, MI, 20133, Italy

Location

Novartis Investigative Site

Rozzano, MI, 20089, Italy

Location

Novartis Investigative Site

Fukuoka, Fukuoka, 811-1395, Japan

Location

Novartis Investigative Site

Sunto Gun, Shizuoka, 411 8777, Japan

Location

Novartis Investigative Site

Singapore, 168583, Singapore

Location

Novartis Investigative Site

Madrid, 28041, Spain

Location

Related Publications (1)

• Ribrag V, Iglesias L, De Braud F, Ma B, Yokota T, Zander T, Spreafico A, Subbiah V, Illert AL, Tan D, Santoro A, Munster PN, Suehiro Y, Wang Y, Ji DM, Chen S, Beltz K, Suenaga N, Ramkumar T, Luo F, Lai C, Wainberg ZA. A first-in-human phase 1/2 dose-escalation study of MAK683 (EED inhibitor) in patients with advanced malignancies. Eur J Cancer. 2025 Feb 5;216:115122. doi: 10.1016/j.ejca.2024.115122. Epub 2024 Nov 16.

  PMID: 39793445 DERIVED

Related Links

• Link to study results

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 2, 2016
• First Posted: September 14, 2016
• Study Start: October 3, 2016
• Primary Completion: October 9, 2024
• Study Completion: October 9, 2024
• Last Updated: August 11, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (2); FR (1); ES (1); DE (2); HK (1); JP (2); SG (1); IT (2); US (3); CA (1)