High Tumor Mutation BurdenPhase 2NCT04098068

Study of MK-3475 (Pembrolizumab) in Patients With Microsatellite Unstable (MSI) Tumors (Cohort D)

A Phase 2 study testing MK-3475 in people with High Tumor Mutation Burden and High TMB (Tumor Mutation Burden), run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 3 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

This study will be looking at whether MK-3475 (pembrolizumab) is effective (anti-tumor activity) and safe in patients with MSI (Microsatellite Unstable) negative cancer with a mutator phenotype. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: High Tumor Mutation Burden, High TMB (Tumor Mutation Burden), MSS (Microsatellite Stable)
What is being tested?: MK-3475
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 12 participants
Where: 3 sitesUnited States
Study dates: 25 Jan 2018to 5 Feb 2025
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

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

Patients with microsatellite stable tumor and a tumor mutation burden (TMB) level measured at > 20 mutations per megabase pairs (MB)
Have measurable disease
Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1
Adequate organ function as defined by study-specified laboratory tests
Must use acceptable form of birth control through the study and for 28 days after final dose of study drug
Signed informed consent form

Show all 11Show fewer

Willing and able to comply with study procedures
Agree to have a biopsy of their cancer
Patients with colon cancer must have received at least two prior cancer therapy regimens.
Patients with other cancer types must have received at least one prior cancer therapy
Progressive disease

Who cannot join

Patients with uncontrolled intercurrent illness, including but not limited to ongoing or active infection, systematic congestive heart failure, unstable angina pectoris, cardiac arrhythmia or psychiatric condition that would limit compliance with study requirements.
Patients who have had chemotherapy or biological cancer therapy within 2 weeks prior to the first dose of study drug
Patients who have had radiation within 2 weeks prior to the first dose of study drug
Patients who have undergone major surgery within 4 weeks of dosing of investigational agent
Patients who have received another investigational product or investigational device within 4 weeks prior to receiving study drug
Patients who have received any of the following concomitant therapy: Interleukin-2 (IL-2), interferon, or other non-study immunotherapy regimens, immunosuppressive agents, other investigational therapies or chronic use of systemic corticosteroids within one week prior to first dose of study drug

Show all 22Show fewer

Patients who have received a live vaccine within 4 weeks prior to or after any dose of MK-3475 (exception: inactivated flu vaccines)
Patients who have received growth factors, including but not limited to granulocyte-colony stimulating factor (G-CSF), granulocyte macrophage-colony stimulating factor (GM-CSF), erythropoietin, etc. within 2 weeks of study drug administration
Patient who have had prior treatment with anti-PD-1 (anti-programmed cell death protein 1), anti-PD-L1, anti-PD-L2, anti-CD137, anti-OX-40, anti-CD40, or anti-CTLA-4 antibodies
Patients with history of any autoimmune disease:inflammatory bowel disease, (including ulcerative colitis and Crohn's Disease), rheumatoid arthritis, systemic progressive sclerosis (scleroderma), systemic lupus erythematosus (SLE) autoimmune vasculitis, central nervous system (CNS) or motor neuropathy considered to be of autoimmune origin.
Patients who have known history of infection with HIV, hepatitis B, or hepatitis C
Patients with evidence of interstitial lung disease
Systemically active steroid use
Patients on home oxygen
Patients with oxygen saturation of <92% on room air by pulse oximetry
Pregnant or lactating
Conditions, including alcohol or drug dependence, or intercurrent illness that would affect the patient's ability to comply with study visits and procedures
Patient with known active central nervous system metastases and/or carcinomatous meningitis.
Patients with primary brain tumors.
Requires any other form of systemic or localized antineoplastic therapy while on study
Has any tissue or organ allograft
Patients with history of allogeneic hematopoeitic stem cell transplant

Trial locations and contacts

3 sites in 1 country.

United States3 sites

Sidney Kimmel Comprehensive Cancer Center
Baltimore, Maryland, 21231
Ohio State University
Columbus, Ohio, 43210
Memorial Sloan Kettering Cancer Center
New York, New York, 10065

Other trials in United States

About this study

Official title: Phase 2 Study of MK-3475 (Pembrolizumab) in Patients With Microsatellite Unstable (MSI) Tumors

This study will be looking at whether MK-3475 (pembrolizumab) is effective (anti-tumor activity) and safe in patients with MSI (Microsatellite Unstable) negative cancer with a mutator phenotype.

Conditions: High Tumor Mutation Burden, High TMB (Tumor Mutation Burden), MSS (Microsatellite Stable)
Being tested: MK-3475
Keywords: Mutation load, Tumor mutation load, Mutation burden, Tumor mutation burden (TMB), Hypermutation, MSI Negative with Mutator Phenotype (High Tumor Mutation Burden), TMB (Tumor Mutation Burden)
Medical subject headings: Spinocerebellar Degenerations

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

MK-3475Drug
Also called Pembrolizumab
MK-3475 (pembrolizumab) 200 mg flat dose every 21 days

Study groups in NCT04098068
Study group	Role	What they receive
MSI (Microsatellite Unstable) Negative with Mutator Phenotype	Experimental	Not described Receives: Drug: MK-3475

What is being measured

The primary outcome is the main question the study is designed to answer.

Objective Response Rate (ORR) in Patients With MSI (Microsatellite Unstable)-Negative Solid Tumor Malignancies With a Mutator Phenotype
Objective Response Rate (ORR) is defined as the number of patients achieving a complete response (CR) or partial response (PR) based on RECIST 1.1 criteria. CR = disappearance of all target lesions, PR is =>30% decrease in sum of diameters of target lesions.
Measured: 2 years

Secondary outcomes (4)

Overall Survival (OS)
OS will be measured from date of first dose until death or end of follow-up (OS will be censored on the date the subject was last known to be alive for subjects without documentation of death at the time of analysis). Estimation based on the Kaplan-Meier curve.
Measured: 80 months
Progression-Free Survival (PFS) in Patients Using RECIST 1.1(Response Evaluation Criteria In Solid Tumors)
PFS is defined as the number of months from the date of first dose to disease progression (progressive disease [PD] or relapse from complete response [CR] as assessed using RECIST 1.1 criteria) or death due to any cause. Per RECIST 1.1 criteria, CR = disappearance of all target lesions, Partial Response (PR) is =>30% decrease in sum of diameters of target lesions, Progressive Disease (PD) is >20% increase in sum of diameters of target lesions, Stable Disease (SD) is <30% decrease or <20% increase in sum of diameters of target lesions. Estimation based on the Kaplan-Meier curve.
Measured: 24 months
Disease Control Rate (DCR)
Disease Control Rate (DCR) is defined as the number of patients achieving a complete response (CR) or partial response (PR) or stable disease (SD) based on RECIST 1.1 criteria. CR = disappearance of all target lesions, PR is =>30% decrease in sum of diameters of target lesions, progressive disease (PD) is >20% increase in sum of diameters of target lesions, stable disease (SD) is <30% decrease or <20% increase in sum of diameters of target lesions.
Measured: 2 years
Number of Patients Experiencing a Grade 3 or Above Treatment-related Toxicity
When calculating the incidence of AEs, each adverse event (AE) (as defined by NCI CTCAE v4.03) will be counted only once for a given subject.
Measured: 28 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

25 Jan 20185 Feb 2025

First posted20 Sep 2019
Study start25 Jan 2018
Primary completion15 May 2022
Study completion5 Feb 2025

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for High Tumor Mutation BurdenStudies of the same condition, open and under way.
More trials run by Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsThe 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 2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 12 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04098068
Sponsor's protocol ID: J1365 (Cohort D)
Other IDs: MK-3475-016, NA_00085756
Status last verified: Mar 2025
First submitted: 19 Sep 2019
Last updated: 30 Mar 2025
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Active, not recruitingPhase 1/2
A Beta-only IL-2 ImmunoTherapY Study
Advanced Solid Tumor, Unresectable Solid Tumor
Active, not recruitingPhase 2
Pembrolizumab With Olaparib as Combined Therapy in Metastatic Pancreatic Cancer
Pancreatic Cancer
RecruitingPhase 2
Isunakinra Alone and in Combination With Pembrolizumab in Patients With Colorectal Cancer (MSS)
Colorectal Cancer Metastatic
Active, not recruitingPhase 1/2
EMITT-1 (ERAP Mediated Immunopeptidome Targeting Trial - 1)
Advanced Solid Malignancy
RecruitingPhase 1
A Phase 1 Study of PLN-101095 in Adults With Advanced or Metastatic Solid Tumors
Advanced or Metastatic Solid Tumor

All High Tumor Mutation Burden trials

Study at a glance

From the registry record, last updated by the sponsor on 30 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Phase 2 Study of MK-3475 (Pembrolizumab) in Patients With Microsatellite Unstable (MSI) Tumors
ClinicalTrials.gov ID: NCT04098068
Acronym / sponsor ID: J1365 (Cohort D)
Conditions: High Tumor Mutation Burden, High TMB (Tumor Mutation Burden), MSS (Microsatellite Stable)
Keywords: Mutation load, Tumor mutation load, Mutation burden, Tumor mutation burden (TMB), Hypermutation, MSI Negative with Mutator Phenotype (High Tumor Mutation Burden), TMB (Tumor Mutation Burden)
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 12 participants (actual)
Lead sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsUniversity, hospital or other
Collaborators: Merck Sharp & Dohme LLC
Study start: 25 Jan 2018 (actual)
Primary completion: 15 May 2022 (actual)
Study completion: 5 Feb 2025 (actual)
First posted: 20 Sep 2019 (actual)
Results: Posted 19 May 2023

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

This study will be looking at whether MK-3475 (pembrolizumab) is effective (anti-tumor activity) and safe in patients with MSI (Microsatellite Unstable) negative cancer with a mutator phenotype.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
MSI (Microsatellite Unstable) Negative with Mutator Phenotype	Experimental	Drug: MK-3475

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (11 listed)

Patients with microsatellite stable tumor and a tumor mutation burden (TMB) level measured at > 20 mutations per megabase pairs (MB)
Have measurable disease
Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1
Adequate organ function as defined by study-specified laboratory tests
Must use acceptable form of birth control through the study and for 28 days after final dose of study drug

Key exclusion criteria (22 listed)

Patients with uncontrolled intercurrent illness, including but not limited to ongoing or active infection, systematic congestive heart failure, unstable angina pectoris, cardiac arrhythmia or psychiatric condition that would limit compliance with study requirements.
Patients who have had chemotherapy or biological cancer therapy within 2 weeks prior to the first dose of study drug
Patients who have had radiation within 2 weeks prior to the first dose of study drug
Patients who have undergone major surgery within 4 weeks of dosing of investigational agent
Patients who have received another investigational product or investigational device within 4 weeks prior to receiving study drug

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
MK-3475Also: PembrolizumabMK-3475 (pembrolizumab) 200 mg flat dose every 21 days	Drug	MSI (Microsatellite Unstable) Negative with Mutator Phenotype

Primary outcome

Objective Response Rate (ORR) in Patients With MSI (Microsatellite Unstable)-Negative Solid Tumor Malignancies With a Mutator Phenotype
Time frame: 2 years
Objective Response Rate (ORR) is defined as the number of patients achieving a complete response (CR) or partial response (PR) based on RECIST 1.1 criteria. CR = disappearance of all target lesions, PR is =>30% decrease in sum of diameters of target lesions.

4 secondary outcomes

Overall Survival (OS)
Time frame: 80 months
Progression-Free Survival (PFS) in Patients Using RECIST 1.1(Response Evaluation Criteria In Solid Tumors)
Time frame: 24 months
Disease Control Rate (DCR)
Time frame: 2 years
Number of Patients Experiencing a Grade 3 or Above Treatment-related Toxicity
Time frame: 28 months

Results and safety

Results posted to the registry on 19 May 2023, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
MSI (Microsatellite Unstable) Negative With Mutator Phenotype	12	2

Primary outcome: Objective Response Rate (ORR) in Patients With MSI (Microsatellite Unstable)-Negative Solid Tumor Malignancies With a Mutator Phenotype

Time frame: 2 years. Count of participants. Unit: Participants

Measure	MSI (Microsatellite Unstable) Negative With Mutator Phenotype n = 11
Value	5

Population analysed: Only 11/12 were evaluable for this outcome

4 secondary outcomes are reported in the full results.

Adverse events

Time frame: Serious and Other Adverse Events assessed for up to 28 months. All-Cause Mortality assessed for up to 80 months.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
MSI (Microsatellite Unstable) Negative With Mutator Phenotype	6 of 12 (50%)	5 of 12 (41.7%)	4 of 12

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 30 Mar 2025.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: No

Related trials for High Tumor Mutation Burden

Active, not recruitingPhase 1/2
A Beta-only IL-2 ImmunoTherapY Study
Advanced Solid Tumor, Unresectable Solid Tumor
Active, not recruitingPhase 2
Pembrolizumab With Olaparib as Combined Therapy in Metastatic Pancreatic Cancer
Pancreatic Cancer
RecruitingPhase 2
Isunakinra Alone and in Combination With Pembrolizumab in Patients With Colorectal Cancer (MSS)
Colorectal Cancer Metastatic
Active, not recruitingPhase 1/2
EMITT-1 (ERAP Mediated Immunopeptidome Targeting Trial - 1)
Advanced Solid Malignancy
RecruitingPhase 1
A Phase 1 Study of PLN-101095 in Adults With Advanced or Metastatic Solid Tumors
Advanced or Metastatic Solid Tumor

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.

Dung Le, MD principal investigator

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

3 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

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 11 inclusion and 22 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: finished, as of the sponsor's last update on 30 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United States. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 19 May 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Objective Response Rate (ORR) in Patients With MSI (Microsatellite Unstable)-Negative Solid Tumor Malignancies With a Mutator Phenotype (time frame: 2 years). 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 NCT04098068.

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 30 Mar 2025.