Diffuse Large B-cell LymphomaPhase 1NCT02900651
Safety and Efficacy of MAK683 in Adult Patients With Advanced Malignancies
A Phase 1 study testing MAK683 in people with Diffuse Large B-cell Lymphoma, run by Novartis Pharmaceuticals at 16 sites in 10 countries.
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Diffuse Large B-cell Lymphoma
- What is being tested?
- MAK683
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 139 participants
- Where
- 16 sitesin 10 countries
- Study dates
- 3 Oct 2016to 9 Oct 2024
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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:
Show all 13Show fewer
- 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
Trial locations and contacts
16 sites in 10 countries.
16 sites in 10 countries
United States3 sites
Uni Of TX MD Anderson Cancer Cntr Dept of Onc
Houston, Texas, 77030
UCSF .
San Francisco, California, 94115
UCLA Santa Monica Hematology Oncology
Santa Monica, California, 90404
China2 sites
Novartis Investigative Site
Chengdu, Sichuan, 610041
Novartis Investigative Site
Shanghai, 200032
Germany2 sites
Novartis Investigative Site
Cologne, 50937
Novartis Investigative Site
Freiburg im Breisgau, 79106
Italy2 sites
Novartis Investigative Site
Milan, MI, 20133
Novartis Investigative Site
Rozzano, MI, 20089
Japan2 sites
Novartis Investigative Site
Fukuoka, Fukuoka, 811-1395
Novartis Investigative Site
Sunto Gun, Shizuoka, 411 8777
About this study
Official title: 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.
Read the 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.
- Conditions
- Diffuse Large B-cell Lymphoma
- Being tested
- MAK683
- Keywords
- MAK683, DLBCL, EED - Embryonic ectoderm development, EZH2 - Enhancer of zeste homolog 2
- Medical subject headings
- Lymphoma, Large B-Cell, Diffuse
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MAK683Drug
Drug: MAK683
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: MAK683 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of dose limiting toxicities (DLTs)
Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs)
Measured: 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
Measured: up to approximately 3 years
Secondary outcomes (8)
Overall Response Rate (ORR)
Measured: up to 30 months
Duration of overall response (DOR)
Measured: up to 30 months
Progression-free survival (PFS)
Measured: up to 30 months
Best Overall Response (BOR)
Measured: up to 30 months
Peak Plasma Concentration (Cmax) of MAK683
Pharmacokinetic profile of MAK683
Measured: 30 months
Area Under the Plasma Concentration (AUC) Time Curve of MAK683
Pharmacokinetic profile of MAK683
Measured: 30 months
Half-Life of MAK683
Pharmacokinetic profile of MAK683
Measured: 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
Measured: up to day 15
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Sep 2016 (estimated)
- Study start3 Oct 2016
- Primary completion9 Oct 2024
- Study completion9 Oct 2024
Why it stopped: The decision of early termination was made due to business reasons, and was not based on any safety or tolerability concerns for MAK683
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Diffuse Large B-cell LymphomaStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 139 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02900651
- Sponsor's protocol ID
- CMAK683X2101
- Other IDs
- 2016-001860-12, 2016
- Status last verified
- Aug 2025
- First submitted
- 2 Sep 2016
- Last updated
- 11 Aug 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: 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
Publications
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.
PubMed 39793445
Study at a glance
From the registry record, last updated by the sponsor on 11 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II, Multicenter, Open-label Study of MAK683 in Adult Patients With Advanced Malignancies
- ClinicalTrials.gov ID
- NCT02900651
- Acronym / sponsor ID
- CMAK683X2101
- Conditions
- Diffuse Large B-cell Lymphoma
- Keywords
- MAK683, DLBCL, EED - Embryonic ectoderm development, EZH2 - Enhancer of zeste homolog 2
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The decision of early termination was made due to business reasons, and was not based on any safety or tolerability concerns for MAK683
- Enrolment
- 139 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 3 Oct 2016 (actual)
- Primary completion
- 9 Oct 2024 (actual)
- Study completion
- 9 Oct 2024 (actual)
- First posted
- 14 Sep 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Phase I - All | Experimental | Drug: MAK683advanced stage (relapsed/refractory or recurrent/metastatic) malignancy limited to the following malignancies; DLBCL, nasopharyngeal carcinoma, gastric cancer, ovarian cancer, prostate cancer and sarcoma. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (13 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MAK683Drug: MAK683 | Drug | Phase I - All |
Primary outcome
Incidence of dose limiting toxicities (DLTs)
Time frame: up to 28 days
Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs)
Safety and tolerability
Time frame: up to approximately 3 years
Incidence and severity of AEs, SAEs, changes in laboratory values, vital signs and ECGs, dose interruptions and reductions
8 secondary outcomes
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
Time frame: 30 months
Area Under the Plasma Concentration (AUC) Time Curve of MAK683
Time frame: 30 months
Half-Life of MAK683
Time frame: 30 months
H3K27 tri methylation level in PBMC
Time frame: up to day 15
Results and safety
The study was stopped early (reason given: The decision of early termination was made due to business reasons, and was not based on any safety or tolerability concerns for MAK683). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Aug 2025.
- Derived from this study: PubMed 39793445Ribrag 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.
- Link to study resultsLink provided by the sponsor.
- Individual participant dataSharing planned: No. 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
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
16 sites in 10 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing MAK683 in people with Diffuse Large B-cell Lymphoma, run by Novartis Pharmaceuticals at 16 sites in 10 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 11 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 16 sites in United States, China, Germany, Italy, Japan and 5 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: The decision of early termination was made due to business reasons, and was not based on any safety or tolerability concerns for MAK683). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of dose limiting toxicities (DLTs) (time frame: up to 28 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02900651, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Aug 2025.