Trial Outcomes & Findings for Study of MK-3475 (Pembrolizumab) in Patients With Microsatellite Unstable (MSI) Tumors (Cohort D) (NCT NCT04098068)

NCT ID: NCT04098068

Last Updated: 2025-03-30

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 12 participants
• Primary outcome timeframe: 2 years
• Results posted on: 2025-03-30

Participant Flow

Participant milestones

Measure	MSI (Microsatellite Unstable) Negative With Mutator Phenotype MK-3475 (pembrolizumab): MK-3475 200 mg flat dose every 21 days
Overall Study STARTED	12
Overall Study COMPLETED	2
Overall Study NOT COMPLETED	10

Reasons for withdrawal

Measure	MSI (Microsatellite Unstable) Negative With Mutator Phenotype MK-3475 (pembrolizumab): MK-3475 200 mg flat dose every 21 days
Overall Study Disease Progression	7
Overall Study Withdrawal by Subject	2
Overall Study New Cancer Diagnosis	1

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	MSI (Microsatellite Unstable) Negative With Mutator Phenotype n=12 Participants MK-3475 (pembrolizumab): MK-3475 200 mg flat dose every 21 days
Age, Categorical <=18 years	0 Participants n=93 Participants
Age, Categorical Between 18 and 65 years	6 Participants n=93 Participants
Age, Categorical >=65 years	6 Participants n=93 Participants
Sex: Female, Male Female	7 Participants n=93 Participants
Sex: Female, Male Male	5 Participants n=93 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=93 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	12 Participants n=93 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants
Race (NIH/OMB) Asian	0 Participants n=93 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants
Race (NIH/OMB) Black or African American	2 Participants n=93 Participants
Race (NIH/OMB) White	10 Participants n=93 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants

PRIMARY outcome

Timeframe: 2 years

Population: Only 11/12 were evaluable for this outcome

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.

Outcome measures

Measure	MSI (Microsatellite Unstable) Negative With Mutator Phenotype n=11 Participants MK-3475 (pembrolizumab): MK-3475 200 mg flat dose every 21 days
Objective Response Rate (ORR) in Patients With MSI (Microsatellite Unstable)-Negative Solid Tumor Malignancies With a Mutator Phenotype	5 Participants

SECONDARY outcome

Timeframe: 80 months

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.

Outcome measures

Measure	MSI (Microsatellite Unstable) Negative With Mutator Phenotype n=12 Participants MK-3475 (pembrolizumab): MK-3475 200 mg flat dose every 21 days
Overall Survival (OS)	41.9 months Interval 9.7 to NA means that there were an insufficient number of events to estimate the upper bound confidence interval

SECONDARY outcome

Timeframe: 24 months

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.

Outcome measures

Measure	MSI (Microsatellite Unstable) Negative With Mutator Phenotype n=12 Participants MK-3475 (pembrolizumab): MK-3475 200 mg flat dose every 21 days
Progression-Free Survival (PFS) in Patients Using RECIST 1.1(Response Evaluation Criteria In Solid Tumors)	6.8 months Interval 2.0 to NA means that there were an insufficient number of events to estimate the upper bound confidence interval

SECONDARY outcome

Timeframe: 2 years

Population: Only 11/12 were evaluable for this outcome

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.

Outcome measures

Measure	MSI (Microsatellite Unstable) Negative With Mutator Phenotype n=11 Participants MK-3475 (pembrolizumab): MK-3475 200 mg flat dose every 21 days
Disease Control Rate (DCR)	7 Participants

SECONDARY outcome

Timeframe: 28 months

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.

Outcome measures

Measure	MSI (Microsatellite Unstable) Negative With Mutator Phenotype n=12 Participants MK-3475 (pembrolizumab): MK-3475 200 mg flat dose every 21 days
Number of Patients Experiencing a Grade 3 or Above Treatment-related Toxicity	0 Participants

Adverse Events

MSI (Microsatellite Unstable) Negative With Mutator Phenotype

Serious events: 6 serious events

Other events: 5 other events

Deaths: 4 deaths

Serious adverse events

Measure	MSI (Microsatellite Unstable) Negative With Mutator Phenotype n=12 participants at risk MK-3475 (pembrolizumab): MK-3475 200 mg flat dose every 21 days
Cardiac disorders Congestive heart failure	8.3% 1/12 • Number of events 1 • Serious and Other Adverse Events assessed for up to 28 months. All-Cause Mortality assessed for up to 80 months.
General disorders Disease progression	16.7% 2/12 • Number of events 2 • Serious and Other Adverse Events assessed for up to 28 months. All-Cause Mortality assessed for up to 80 months.
Injury, poisoning and procedural complications Opioid use disorder	8.3% 1/12 • Number of events 1 • Serious and Other Adverse Events assessed for up to 28 months. All-Cause Mortality assessed for up to 80 months.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Plasma cell myeloma	8.3% 1/12 • Number of events 1 • Serious and Other Adverse Events assessed for up to 28 months. All-Cause Mortality assessed for up to 80 months.
Respiratory, thoracic and mediastinal disorders Pneumonia	8.3% 1/12 • Number of events 1 • Serious and Other Adverse Events assessed for up to 28 months. All-Cause Mortality assessed for up to 80 months.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Diffuse large B cell lymphoma	8.3% 1/12 • Number of events 1 • Serious and Other Adverse Events assessed for up to 28 months. All-Cause Mortality assessed for up to 80 months.
Vascular disorders Thromboembolic event	8.3% 1/12 • Number of events 1 • Serious and Other Adverse Events assessed for up to 28 months. All-Cause Mortality assessed for up to 80 months.

Other adverse events

Measure	MSI (Microsatellite Unstable) Negative With Mutator Phenotype n=12 participants at risk MK-3475 (pembrolizumab): MK-3475 200 mg flat dose every 21 days
Gastrointestinal disorders Abdominal pain	41.7% 5/12 • Number of events 6 • Serious and Other Adverse Events assessed for up to 28 months. All-Cause Mortality assessed for up to 80 months.
Blood and lymphatic system disorders Anemia	25.0% 3/12 • Number of events 3 • Serious and Other Adverse Events assessed for up to 28 months. All-Cause Mortality assessed for up to 80 months.
Gastrointestinal disorders Anorexia	16.7% 2/12 • Number of events 2 • Serious and Other Adverse Events assessed for up to 28 months. All-Cause Mortality assessed for up to 80 months.
Musculoskeletal and connective tissue disorders Arthralgia	8.3% 1/12 • Number of events 1 • Serious and Other Adverse Events assessed for up to 28 months. All-Cause Mortality assessed for up to 80 months.
Gastrointestinal disorders Ascites	16.7% 2/12 • Number of events 2 • Serious and Other Adverse Events assessed for up to 28 months. All-Cause Mortality assessed for up to 80 months.
Investigations Aspartate aminotransferase increased	8.3% 1/12 • Number of events 1 • Serious and Other Adverse Events assessed for up to 28 months. All-Cause Mortality assessed for up to 80 months.
Musculoskeletal and connective tissue disorders Back pain	25.0% 3/12 • Number of events 3 • Serious and Other Adverse Events assessed for up to 28 months. All-Cause Mortality assessed for up to 80 months.
Cardiac disorders Bradycardia	8.3% 1/12 • Number of events 1 • Serious and Other Adverse Events assessed for up to 28 months. All-Cause Mortality assessed for up to 80 months.
Immune system disorders Cellulitis	8.3% 1/12 • Number of events 1 • Serious and Other Adverse Events assessed for up to 28 months. All-Cause Mortality assessed for up to 80 months.
General disorders Chills	16.7% 2/12 • Number of events 2 • Serious and Other Adverse Events assessed for up to 28 months. All-Cause Mortality assessed for up to 80 months.
Eye disorders Conjunctival erythema	8.3% 1/12 • Number of events 1 • Serious and Other Adverse Events assessed for up to 28 months. All-Cause Mortality assessed for up to 80 months.
Gastrointestinal disorders Constipation	25.0% 3/12 • Number of events 3 • Serious and Other Adverse Events assessed for up to 28 months. All-Cause Mortality assessed for up to 80 months.
Respiratory, thoracic and mediastinal disorders Cough	16.7% 2/12 • Number of events 2 • Serious and Other Adverse Events assessed for up to 28 months. All-Cause Mortality assessed for up to 80 months.
Infections and infestations COVID infection	8.3% 1/12 • Number of events 1 • Serious and Other Adverse Events assessed for up to 28 months. All-Cause Mortality assessed for up to 80 months.
Gastrointestinal disorders Dehydration	8.3% 1/12 • Number of events 2 • Serious and Other Adverse Events assessed for up to 28 months. All-Cause Mortality assessed for up to 80 months.
Gastrointestinal disorders Dental pain	8.3% 1/12 • Number of events 1 • Serious and Other Adverse Events assessed for up to 28 months. All-Cause Mortality assessed for up to 80 months.
Psychiatric disorders Depression	8.3% 1/12 • Number of events 1 • Serious and Other Adverse Events assessed for up to 28 months. All-Cause Mortality assessed for up to 80 months.
Endocrine disorders Diabetes mellitus	8.3% 1/12 • Number of events 1 • Serious and Other Adverse Events assessed for up to 28 months. All-Cause Mortality assessed for up to 80 months.
Gastrointestinal disorders Diarrhea	25.0% 3/12 • Number of events 6 • Serious and Other Adverse Events assessed for up to 28 months. All-Cause Mortality assessed for up to 80 months.
Eye disorders Dry eye	8.3% 1/12 • Number of events 1 • Serious and Other Adverse Events assessed for up to 28 months. All-Cause Mortality assessed for up to 80 months.
Skin and subcutaneous tissue disorders Dry skin	8.3% 1/12 • Number of events 1 • Serious and Other Adverse Events assessed for up to 28 months. All-Cause Mortality assessed for up to 80 months.
Gastrointestinal disorders Dysphagia	8.3% 1/12 • Number of events 2 • Serious and Other Adverse Events assessed for up to 28 months. All-Cause Mortality assessed for up to 80 months.
Respiratory, thoracic and mediastinal disorders Dyspnea	8.3% 1/12 • Number of events 1 • Serious and Other Adverse Events assessed for up to 28 months. All-Cause Mortality assessed for up to 80 months.
General disorders Edema	25.0% 3/12 • Number of events 4 • Serious and Other Adverse Events assessed for up to 28 months. All-Cause Mortality assessed for up to 80 months.
Respiratory, thoracic and mediastinal disorders Epistaxis	8.3% 1/12 • Number of events 1 • Serious and Other Adverse Events assessed for up to 28 months. All-Cause Mortality assessed for up to 80 months.
Gastrointestinal disorders Esophageal dysmotility	8.3% 1/12 • Number of events 1 • Serious and Other Adverse Events assessed for up to 28 months. All-Cause Mortality assessed for up to 80 months.
Gastrointestinal disorders Esophagitis	8.3% 1/12 • Number of events 1 • Serious and Other Adverse Events assessed for up to 28 months. All-Cause Mortality assessed for up to 80 months.
Injury, poisoning and procedural complications Fall	8.3% 1/12 • Number of events 1 • Serious and Other Adverse Events assessed for up to 28 months. All-Cause Mortality assessed for up to 80 months.
General disorders Fatigue	41.7% 5/12 • Number of events 7 • Serious and Other Adverse Events assessed for up to 28 months. All-Cause Mortality assessed for up to 80 months.
General disorders Fever	8.3% 1/12 • Number of events 1 • Serious and Other Adverse Events assessed for up to 28 months. All-Cause Mortality assessed for up to 80 months.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Ganglion cyst	8.3% 1/12 • Number of events 1 • Serious and Other Adverse Events assessed for up to 28 months. All-Cause Mortality assessed for up to 80 months.
Gastrointestinal disorders Gastritis	8.3% 1/12 • Number of events 1 • Serious and Other Adverse Events assessed for up to 28 months. All-Cause Mortality assessed for up to 80 months.
Gastrointestinal disorders Gastroesophageal reflux	8.3% 1/12 • Number of events 1 • Serious and Other Adverse Events assessed for up to 28 months. All-Cause Mortality assessed for up to 80 months.
Nervous system disorders Headache	8.3% 1/12 • Number of events 2 • Serious and Other Adverse Events assessed for up to 28 months. All-Cause Mortality assessed for up to 80 months.
Injury, poisoning and procedural complications Hernia	8.3% 1/12 • Number of events 1 • Serious and Other Adverse Events assessed for up to 28 months. All-Cause Mortality assessed for up to 80 months.
Investigations Hyperbilirubinemia	8.3% 1/12 • Number of events 1 • Serious and Other Adverse Events assessed for up to 28 months. All-Cause Mortality assessed for up to 80 months.
Metabolism and nutrition disorders Hyperglycemia	8.3% 1/12 • Number of events 1 • Serious and Other Adverse Events assessed for up to 28 months. All-Cause Mortality assessed for up to 80 months.
Metabolism and nutrition disorders Hypoalbuminemia	16.7% 2/12 • Number of events 2 • Serious and Other Adverse Events assessed for up to 28 months. All-Cause Mortality assessed for up to 80 months.
Metabolism and nutrition disorders Hyponatremia	8.3% 1/12 • Number of events 1 • Serious and Other Adverse Events assessed for up to 28 months. All-Cause Mortality assessed for up to 80 months.
Vascular disorders Hypotension	8.3% 1/12 • Number of events 1 • Serious and Other Adverse Events assessed for up to 28 months. All-Cause Mortality assessed for up to 80 months.
Endocrine disorders Hypothyroidism	8.3% 1/12 • Number of events 1 • Serious and Other Adverse Events assessed for up to 28 months. All-Cause Mortality assessed for up to 80 months.
Blood and lymphatic system disorders Lymphadenopathy	8.3% 1/12 • Number of events 1 • Serious and Other Adverse Events assessed for up to 28 months. All-Cause Mortality assessed for up to 80 months.
Investigations Lymphocyte count decreased	8.3% 1/12 • Number of events 3 • Serious and Other Adverse Events assessed for up to 28 months. All-Cause Mortality assessed for up to 80 months.
Reproductive system and breast disorders Metrorrhagia	8.3% 1/12 • Number of events 1 • Serious and Other Adverse Events assessed for up to 28 months. All-Cause Mortality assessed for up to 80 months.
Musculoskeletal and connective tissue disorders Myalgia	8.3% 1/12 • Number of events 1 • Serious and Other Adverse Events assessed for up to 28 months. All-Cause Mortality assessed for up to 80 months.
Respiratory, thoracic and mediastinal disorders Nasal congestion	8.3% 1/12 • Number of events 3 • Serious and Other Adverse Events assessed for up to 28 months. All-Cause Mortality assessed for up to 80 months.
Gastrointestinal disorders Nausea	25.0% 3/12 • Number of events 6 • Serious and Other Adverse Events assessed for up to 28 months. All-Cause Mortality assessed for up to 80 months.
Musculoskeletal and connective tissue disorders Neck pain	8.3% 1/12 • Number of events 1 • Serious and Other Adverse Events assessed for up to 28 months. All-Cause Mortality assessed for up to 80 months.
General disorders Non-cardiac chest pain	25.0% 3/12 • Number of events 4 • Serious and Other Adverse Events assessed for up to 28 months. All-Cause Mortality assessed for up to 80 months.
Renal and urinary disorders Nocturia	8.3% 1/12 • Number of events 1 • Serious and Other Adverse Events assessed for up to 28 months. All-Cause Mortality assessed for up to 80 months.
Infections and infestations Oral thrush	8.3% 1/12 • Number of events 1 • Serious and Other Adverse Events assessed for up to 28 months. All-Cause Mortality assessed for up to 80 months.
Musculoskeletal and connective tissue disorders Pain	8.3% 1/12 • Number of events 2 • Serious and Other Adverse Events assessed for up to 28 months. All-Cause Mortality assessed for up to 80 months.
Musculoskeletal and connective tissue disorders Pain in extremity	16.7% 2/12 • Number of events 3 • Serious and Other Adverse Events assessed for up to 28 months. All-Cause Mortality assessed for up to 80 months.
Musculoskeletal and connective tissue disorders Pelvic pain	8.3% 1/12 • Number of events 1 • Serious and Other Adverse Events assessed for up to 28 months. All-Cause Mortality assessed for up to 80 months.
Investigations Platelet count decreased	8.3% 1/12 • Number of events 2 • Serious and Other Adverse Events assessed for up to 28 months. All-Cause Mortality assessed for up to 80 months.
Respiratory, thoracic and mediastinal disorders Pneumonitis	8.3% 1/12 • Number of events 1 • Serious and Other Adverse Events assessed for up to 28 months. All-Cause Mortality assessed for up to 80 months.
Skin and subcutaneous tissue disorders Pruritis	25.0% 3/12 • Number of events 4 • Serious and Other Adverse Events assessed for up to 28 months. All-Cause Mortality assessed for up to 80 months.
Skin and subcutaneous tissue disorders Rash	16.7% 2/12 • Number of events 3 • Serious and Other Adverse Events assessed for up to 28 months. All-Cause Mortality assessed for up to 80 months.
Respiratory, thoracic and mediastinal disorders Sinus pain	8.3% 1/12 • Number of events 2 • Serious and Other Adverse Events assessed for up to 28 months. All-Cause Mortality assessed for up to 80 months.
Gastrointestinal disorders Small bowel obstruction	8.3% 1/12 • Number of events 1 • Serious and Other Adverse Events assessed for up to 28 months. All-Cause Mortality assessed for up to 80 months.
Skin and subcutaneous tissue disorders Sweating	8.3% 1/12 • Number of events 1 • Serious and Other Adverse Events assessed for up to 28 months. All-Cause Mortality assessed for up to 80 months.
Vascular disorders Thromboembolic event	8.3% 1/12 • Number of events 1 • Serious and Other Adverse Events assessed for up to 28 months. All-Cause Mortality assessed for up to 80 months.
Ear and labyrinth disorders Tinnitus	8.3% 1/12 • Number of events 1 • Serious and Other Adverse Events assessed for up to 28 months. All-Cause Mortality assessed for up to 80 months.
Infections and infestations Upper respiratory infection	8.3% 1/12 • Number of events 1 • Serious and Other Adverse Events assessed for up to 28 months. All-Cause Mortality assessed for up to 80 months.
Renal and urinary disorders Urinary tract pain	16.7% 2/12 • Number of events 2 • Serious and Other Adverse Events assessed for up to 28 months. All-Cause Mortality assessed for up to 80 months.
Reproductive system and breast disorders Vaginal hemorrhage	8.3% 1/12 • Number of events 1 • Serious and Other Adverse Events assessed for up to 28 months. All-Cause Mortality assessed for up to 80 months.
Ear and labyrinth disorders Vertigo	8.3% 1/12 • Number of events 1 • Serious and Other Adverse Events assessed for up to 28 months. All-Cause Mortality assessed for up to 80 months.
Gastrointestinal disorders Vomiting	25.0% 3/12 • Number of events 14 • Serious and Other Adverse Events assessed for up to 28 months. All-Cause Mortality assessed for up to 80 months.
Eye disorders Watering eyes	8.3% 1/12 • Number of events 1 • Serious and Other Adverse Events assessed for up to 28 months. All-Cause Mortality assessed for up to 80 months.
Investigations Weight loss	16.7% 2/12 • Number of events 3 • Serious and Other Adverse Events assessed for up to 28 months. All-Cause Mortality assessed for up to 80 months.

Additional Information

Dung Le, MD

Sidney Kimmel Comprehensive Center at Johns Hopkins University

Phone: 443-287-0002

Email: dle@jhmi.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place