Trial Outcomes & Findings for Study of MK-3475 in Patients With Microsatellite Unstable (MSI) Tumors (Cohorts A, B and C) (NCT NCT01876511)

NCT ID: NCT01876511

Last Updated: 2020-02-06

Results Overview

For Cohorts A and B: irPFS rate is defined as the percentage of patients with disease progression (irPD or relapse from irCR as assessed using irRC criteria) or death due to any cause at 20 weeks. Per irRC criteria, Complete Response (irCR) is the disappearance of all target lesions, Partial Response (irPR) is a decrease in tumor burden by 50% or greater by a consecutive assessment at least 4 weeks after first documentation, Stable Disease (irSD) is the failure to meet criteria for irCR or irPR (in absence of irPD), Progressive Disease (irPD) is at least 25% increase in tumor burden relative to nadir. Estimation based on the Kaplan-Meier curve.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 113 participants
• Primary outcome timeframe: 20 weeks
• Results posted on: 2020-02-06

Participant Flow

Participant milestones

Measure	Cohort A: MSI Positive Colorectal Cancer MK-3475: MK-3475 10 mg/kg every 14 days	Cohort B: MSI Negative Colorectal Cancer MK-3475: MK-3475 10 mg/kg every 14 days	Cohort C: MSI Positive Non-Colorectal Cancer MK-3475: MK-3475 10 mg/kg every 14 days
Overall Study STARTED	41	25	47
Overall Study Stages 1 and 2	24	25	21
Overall Study COMPLETED	18	0	16
Overall Study NOT COMPLETED	23	25	31

Reasons for withdrawal

Measure	Cohort A: MSI Positive Colorectal Cancer MK-3475: MK-3475 10 mg/kg every 14 days	Cohort B: MSI Negative Colorectal Cancer MK-3475: MK-3475 10 mg/kg every 14 days	Cohort C: MSI Positive Non-Colorectal Cancer MK-3475: MK-3475 10 mg/kg every 14 days
Overall Study Disease Progression-clinical/radiologic	11	24	16
Overall Study Death (unrelated)	3	0	2
Overall Study Drug-related Toxicity	5	1	6
Overall Study Patient Decision	3	0	6
Overall Study Physician Decision	1	0	1

Baseline Characteristics

Study of MK-3475 in Patients With Microsatellite Unstable (MSI) Tumors (Cohorts A, B and C)

Baseline characteristics by cohort

Measure	Cohort A: MSI Positive Colorectal Cancer n=41 Participants MK-3475: MK-3475 10 mg/kg every 14 days	Cohort B: MSI Negative Colorectal Cancer n=25 Participants MK-3475: MK-3475 10 mg/kg every 14 days	Cohort C: MSI Positive Non-Colorectal Cancer n=47 Participants MK-3475: MK-3475 10 mg/kg every 14 days	Total n=113 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	31 Participants n=5 Participants	15 Participants n=7 Participants	30 Participants n=5 Participants	76 Participants n=4 Participants
Age, Categorical >=65 years	10 Participants n=5 Participants	10 Participants n=7 Participants	17 Participants n=5 Participants	37 Participants n=4 Participants
Sex: Female, Male Female	19 Participants n=5 Participants	9 Participants n=7 Participants	23 Participants n=5 Participants	51 Participants n=4 Participants
Sex: Female, Male Male	22 Participants n=5 Participants	16 Participants n=7 Participants	24 Participants n=5 Participants	62 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	4 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	39 Participants n=5 Participants	25 Participants n=7 Participants	44 Participants n=5 Participants	108 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	3 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	6 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	3 Participants n=5 Participants	3 Participants n=7 Participants	1 Participants n=5 Participants	7 Participants n=4 Participants
Race (NIH/OMB) White	34 Participants n=5 Participants	21 Participants n=7 Participants	44 Participants n=5 Participants	99 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants

PRIMARY outcome

Timeframe: 20 weeks

Population: It was a pre-specified objective to complete this objective in Cohort A and B only. Per protocol during stages 1 and 2, the study enrollment goal was 25 for Cohort A and B. However, only 24 subjects were enrolled in Cohort A. Additional subjects for this study were enrolled during the second expansion portion of this protocol.

For Cohorts A and B: irPFS rate is defined as the percentage of patients with disease progression (irPD or relapse from irCR as assessed using irRC criteria) or death due to any cause at 20 weeks. Per irRC criteria, Complete Response (irCR) is the disappearance of all target lesions, Partial Response (irPR) is a decrease in tumor burden by 50% or greater by a consecutive assessment at least 4 weeks after first documentation, Stable Disease (irSD) is the failure to meet criteria for irCR or irPR (in absence of irPD), Progressive Disease (irPD) is at least 25% increase in tumor burden relative to nadir. Estimation based on the Kaplan-Meier curve.

Outcome measures

Measure	Cohort A: MSI Positive Colorectal Cancer n=24 Participants MK-3475: MK-3475 10 mg/kg every 14 days	Cohort B: MSI Negative Colorectal Cancer n=25 Participants MK-3475: MK-3475 10 mg/kg every 14 days	Cohort C: MSI Positive Non-Colorectal Cancer MK-3475: MK-3475 10 mg/kg every 14 days
Immune-related Progression Free Survival (irPFS) at 20 Weeks in MSI Positive and Negative Colorectal Adenocarcinoma Participants Using Immune Related Response Criteria (irRC) During Stages 1 and 2	88 percentage of participants Interval 75.0 to 100.0	12 percentage of participants Interval 4.0 to 36.0	—

PRIMARY outcome

Timeframe: 28 months

Population: It was a pre-specified objective to complete this objective in Cohort A and B only. Per protocol during stages 1 and 2, the study enrollment goal was 25 for Cohort A and B. However, only 24 subjects were enrolled in Cohort A. Additional subjects for this study were enrolled during the second expansion portion of this protocol.

For Cohorts A and B: Immune-related Objective Response Rate (irORR) is defined as the percentage of patients achieving a complete response (irCR) or partial response (irPR) based on irRC criteria. Per irRC criteria, Complete Response (irCR) is the disappearance of all target lesions, Partial Response (irPR) is a decrease in tumor burden by 50% or greater by a consecutive assessment at least 4 weeks after first documentation.

Outcome measures

Measure	Cohort A: MSI Positive Colorectal Cancer n=24 Participants MK-3475: MK-3475 10 mg/kg every 14 days	Cohort B: MSI Negative Colorectal Cancer n=25 Participants MK-3475: MK-3475 10 mg/kg every 14 days	Cohort C: MSI Positive Non-Colorectal Cancer MK-3475: MK-3475 10 mg/kg every 14 days
Immune-related Objective Response Rate in MSI Positive and Negative Colorectal Adenocarcinoma Participants Using Immune Related Response Criteria (irRC) During Stages 1 and 2	67 percentage of participants Interval 45.0 to 84.0	0 percentage of participants Interval 0.0 to 14.0	—

PRIMARY outcome

Timeframe: 20 weeks

Population: It was a pre-specified objective to complete this objective in Cohort C only. Per protocol during stages 1 and 2, the study enrollment goal was 21 for Cohort C. Additional subjects for this study were enrolled during the second expansion portion of this protocol.

For Cohort C: irPFS rate is defined as the percentage of patients with disease progression (irPD or relapse from irCR as assessed using irRC criteria) or death due to any cause at 20 weeks. Per irRC criteria, Complete Response (irCR) is the disappearance of all target lesions, Partial Response (irPR) is a decrease in tumor burden by 50% or greater by a consecutive assessment at least 4 weeks after first documentation, Stable Disease (irSD) is the failure to meet criteria for irCR or irPR (in absence of irPD), Progressive Disease (irPD) is at least 25% increase in tumor burden relative to nadir. Estimation based on the Kaplan-Meier curve.

Outcome measures

Measure	Cohort A: MSI Positive Colorectal Cancer n=21 Participants MK-3475: MK-3475 10 mg/kg every 14 days	Cohort B: MSI Negative Colorectal Cancer MK-3475: MK-3475 10 mg/kg every 14 days	Cohort C: MSI Positive Non-Colorectal Cancer MK-3475: MK-3475 10 mg/kg every 14 days
Immune-related Progression Free Survival (irPFS) at 20 Weeks in MSI Positive Non-colorectal Adenocarcinoma Participants Using Immune Related Response Criteria (irRC) During Stages 1 and 2	67 percentage of participants Interval 49.0 to 90.0	—	—

PRIMARY outcome

Timeframe: 28 months

Population: It was a pre-specified objective to complete this objective in Cohort A and C only.

For Cohorts A and C: Objective Response Rate (ORR) is defined as the percentage 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	Cohort A: MSI Positive Colorectal Cancer n=41 Participants MK-3475: MK-3475 10 mg/kg every 14 days	Cohort B: MSI Negative Colorectal Cancer n=47 Participants MK-3475: MK-3475 10 mg/kg every 14 days	Cohort C: MSI Positive Non-Colorectal Cancer MK-3475: MK-3475 10 mg/kg every 14 days
Objective Response Rate in MSI Positive Solid Tumor Malignancies Using Response Evaluation Criteria in Solid Tumors (RECIST 1.1)	54 percentage of participants Interval 37.0 to 69.0	55 percentage of participants Interval 40.0 to 70.0	—

PRIMARY outcome

Timeframe: 20 weeks

Population: It was a pre-specified objective to complete this objective in Cohort A and C only.

For Cohorts A and C: PFS is defined as the percentage of patients with disease progression (PD or relapse from CR as assessed using RECIST 1.1 criteria) or death due to any cause at 20 weeks. 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	Cohort A: MSI Positive Colorectal Cancer n=41 Participants MK-3475: MK-3475 10 mg/kg every 14 days	Cohort B: MSI Negative Colorectal Cancer n=47 Participants MK-3475: MK-3475 10 mg/kg every 14 days	Cohort C: MSI Positive Non-Colorectal Cancer MK-3475: MK-3475 10 mg/kg every 14 days
Progression Free Survival (PFS) at 20 Weeks in MSI Positive Solid Tumor Malignancies Using Response Evaluation Criteria in Solid Tumors (RECIST 1.1)	75 percentage of participants Interval 63.0 to 90.0	68 percentage of participants Interval 56.0 to 83.0	—

SECONDARY outcome

Timeframe: 4 years

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	Cohort A: MSI Positive Colorectal Cancer n=41 Participants MK-3475: MK-3475 10 mg/kg every 14 days	Cohort B: MSI Negative Colorectal Cancer n=25 Participants MK-3475: MK-3475 10 mg/kg every 14 days	Cohort C: MSI Positive Non-Colorectal Cancer n=47 Participants MK-3475: MK-3475 10 mg/kg every 14 days
Overall Survival (OS)	NA Weeks Interval 151.86 to NA means that the median overall survival and upper bound confidence interval was not reached.	36.71 Weeks Interval 21.29 to 69.43	148.86 Weeks Interval 94.71 to NA means that the upper bound confidence interval was not reached.

SECONDARY outcome

Timeframe: 28 weeks

irPFS rate is defined as the percentage of patients with disease progression (irPD or relapse from irCR as assessed using irRC criteria) or death due to any cause at 28 weeks. Per irRC criteria, Complete Response (irCR) is the disappearance of all target lesions, Partial Response (irPR) is a decrease in tumor burden by 50% or greater by a consecutive assessment at least 4 weeks after first documentation, Stable Disease (irSD) is the failure to meet criteria for irCR or irPR (in absence of irPD), Progressive Disease (irPD) is at least 25% increase in tumor burden relative to nadir. Estimation based on the Kaplan-Meier curve.

Outcome measures

Measure	Cohort A: MSI Positive Colorectal Cancer n=41 Participants MK-3475: MK-3475 10 mg/kg every 14 days	Cohort B: MSI Negative Colorectal Cancer n=25 Participants MK-3475: MK-3475 10 mg/kg every 14 days	Cohort C: MSI Positive Non-Colorectal Cancer n=47 Participants MK-3475: MK-3475 10 mg/kg every 14 days
Immune-related Progression Free Survival (irPFS) at 28 Weeks in MSI Positive and Negative Solid Tumor Malignancies Using Immune Related Response Criteria (irRC)	70 percentage of participants Interval 58.0 to 86.0	12 percentage of participants Interval 4.0 to 36.0	64 percentage of participants Interval 51.0 to 80.0

SECONDARY outcome

Timeframe: 28 months

ORR is defined as the percentage 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	Cohort A: MSI Positive Colorectal Cancer n=41 Participants MK-3475: MK-3475 10 mg/kg every 14 days	Cohort B: MSI Negative Colorectal Cancer n=25 Participants MK-3475: MK-3475 10 mg/kg every 14 days	Cohort C: MSI Positive Non-Colorectal Cancer n=47 Participants MK-3475: MK-3475 10 mg/kg every 14 days
Objective Response Rate (ORR) in MSI Positive and Negative Solid Tumor Malignancies Using Response Evaluation Criteria in Solid Tumors (RECIST 1.1)	54 percentage of participants Interval 37.0 to 69.0	0 percentage of participants Interval 0.0 to 14.0	55 percentage of participants Interval 40.0 to 70.0

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	Cohort A: MSI Positive Colorectal Cancer n=41 Participants MK-3475: MK-3475 10 mg/kg every 14 days	Cohort B: MSI Negative Colorectal Cancer n=25 Participants MK-3475: MK-3475 10 mg/kg every 14 days	Cohort C: MSI Positive Non-Colorectal Cancer n=47 Participants MK-3475: MK-3475 10 mg/kg every 14 days
Number of Patients Experiencing a Grade 3 or Above Treatment-related Toxicity	12 Participants	0 Participants	13 Participants

SECONDARY outcome

Timeframe: 28 weeks

PFS is defined as the percentage of patients with disease progression (PD or relapse from CR as assessed using RECIST 1.1 criteria) or death due to any cause at 28 weeks. 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	Cohort A: MSI Positive Colorectal Cancer n=41 Participants MK-3475: MK-3475 10 mg/kg every 14 days	Cohort B: MSI Negative Colorectal Cancer n=25 Participants MK-3475: MK-3475 10 mg/kg every 14 days	Cohort C: MSI Positive Non-Colorectal Cancer n=47 Participants MK-3475: MK-3475 10 mg/kg every 14 days
Progression Free Survival (PFS) at 28 Weeks in MSI Positive and Negative Solid Tumor Malignancies Using Response Evaluation Criteria in Solid Tumors (RECIST 1.1)	70 percentage of participants Interval 57.0 to 86.0	16 percentage of participants Interval 6.0 to 41.0	64 percentage of participants Interval 51.0 to 79.0

SECONDARY outcome

Timeframe: 28 months

Disease Control Rate (DCR) is defined as the percentage 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	Cohort A: MSI Positive Colorectal Cancer n=41 Participants MK-3475: MK-3475 10 mg/kg every 14 days	Cohort B: MSI Negative Colorectal Cancer n=25 Participants MK-3475: MK-3475 10 mg/kg every 14 days	Cohort C: MSI Positive Non-Colorectal Cancer n=47 Participants MK-3475: MK-3475 10 mg/kg every 14 days
Disease Control Rate in MSI Positive and Negative Solid Tumor Malignancies Using Response Evaluation Criteria in Solid Tumors (RECIST 1.1)	80 percentage of participants Interval 65.0 to 91.0	16 percentage of participants Interval 5.0 to 36.0	70 percentage of participants Interval 55.0 to 83.0

SECONDARY outcome

Timeframe: 28 months

ORR was used to determine whether MSI is a marker that predicts treatment response. This is the same data presented in outcome measure number 8 (ORR, to test against null of 5%).

Outcome measures

Measure	Cohort A: MSI Positive Colorectal Cancer n=41 Participants MK-3475: MK-3475 10 mg/kg every 14 days	Cohort B: MSI Negative Colorectal Cancer n=25 Participants MK-3475: MK-3475 10 mg/kg every 14 days	Cohort C: MSI Positive Non-Colorectal Cancer n=47 Participants MK-3475: MK-3475 10 mg/kg every 14 days
Does MSI as a Marker Predict Treatment Response	54 percentage of participants Interval 37.0 to 69.0	0 percentage of participants Interval 0.0 to 14.0	55 percentage of participants Interval 40.0 to 70.0

Adverse Events

Cohort A: MSI Positive Colorectal Cancer

Serious events: 4 serious events

Other events: 41 other events

Deaths: 3 deaths

Cohort B: MSI Negative Colorectal Cancer

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Cohort C: MSI Positive Non-Colorectal Cancer

Serious events: 7 serious events

Other events: 47 other events

Deaths: 2 deaths

Serious adverse events

Measure	Cohort A: MSI Positive Colorectal Cancer n=41 participants at risk MK-3475: MK-3475 10 mg/kg every 14 days	Cohort B: MSI Negative Colorectal Cancer n=25 participants at risk MK-3475: MK-3475 10 mg/kg every 14 days	Cohort C: MSI Positive Non-Colorectal Cancer n=47 participants at risk MK-3475: MK-3475 10 mg/kg every 14 days
Renal and urinary disorders Acute kidney injury	2.4% 1/41 • Number of events 1 • 2 years 4 months Study treatment was administered for up to 2 years. Adverse events were accessed through 90 days after the last dose of study treatment.	0.00% 0/25 • 2 years 4 months Study treatment was administered for up to 2 years. Adverse events were accessed through 90 days after the last dose of study treatment.	0.00% 0/47 • 2 years 4 months Study treatment was administered for up to 2 years. Adverse events were accessed through 90 days after the last dose of study treatment.
Musculoskeletal and connective tissue disorders Arthritis	2.4% 1/41 • Number of events 1 • 2 years 4 months Study treatment was administered for up to 2 years. Adverse events were accessed through 90 days after the last dose of study treatment.	0.00% 0/25 • 2 years 4 months Study treatment was administered for up to 2 years. Adverse events were accessed through 90 days after the last dose of study treatment.	0.00% 0/47 • 2 years 4 months Study treatment was administered for up to 2 years. Adverse events were accessed through 90 days after the last dose of study treatment.
Gastrointestinal disorders Pancreatitis	2.4% 1/41 • Number of events 1 • 2 years 4 months Study treatment was administered for up to 2 years. Adverse events were accessed through 90 days after the last dose of study treatment.	0.00% 0/25 • 2 years 4 months Study treatment was administered for up to 2 years. Adverse events were accessed through 90 days after the last dose of study treatment.	2.1% 1/47 • Number of events 1 • 2 years 4 months Study treatment was administered for up to 2 years. Adverse events were accessed through 90 days after the last dose of study treatment.
Gastrointestinal disorders Diarrhea	0.00% 0/41 • 2 years 4 months Study treatment was administered for up to 2 years. Adverse events were accessed through 90 days after the last dose of study treatment.	0.00% 0/25 • 2 years 4 months Study treatment was administered for up to 2 years. Adverse events were accessed through 90 days after the last dose of study treatment.	2.1% 1/47 • Number of events 1 • 2 years 4 months Study treatment was administered for up to 2 years. Adverse events were accessed through 90 days after the last dose of study treatment.
Gastrointestinal disorders Colitis	0.00% 0/41 • 2 years 4 months Study treatment was administered for up to 2 years. Adverse events were accessed through 90 days after the last dose of study treatment.	0.00% 0/25 • 2 years 4 months Study treatment was administered for up to 2 years. Adverse events were accessed through 90 days after the last dose of study treatment.	2.1% 1/47 • Number of events 1 • 2 years 4 months Study treatment was administered for up to 2 years. Adverse events were accessed through 90 days after the last dose of study treatment.
Cardiac disorders Myocarditis	2.4% 1/41 • Number of events 1 • 2 years 4 months Study treatment was administered for up to 2 years. Adverse events were accessed through 90 days after the last dose of study treatment.	0.00% 0/25 • 2 years 4 months Study treatment was administered for up to 2 years. Adverse events were accessed through 90 days after the last dose of study treatment.	2.1% 1/47 • Number of events 1 • 2 years 4 months Study treatment was administered for up to 2 years. Adverse events were accessed through 90 days after the last dose of study treatment.
Metabolism and nutrition disorders Diabetic ketoacidosis	0.00% 0/41 • 2 years 4 months Study treatment was administered for up to 2 years. Adverse events were accessed through 90 days after the last dose of study treatment.	0.00% 0/25 • 2 years 4 months Study treatment was administered for up to 2 years. Adverse events were accessed through 90 days after the last dose of study treatment.	4.3% 2/47 • Number of events 2 • 2 years 4 months Study treatment was administered for up to 2 years. Adverse events were accessed through 90 days after the last dose of study treatment.
Product Issues Infusion reaction	2.4% 1/41 • Number of events 1 • 2 years 4 months Study treatment was administered for up to 2 years. Adverse events were accessed through 90 days after the last dose of study treatment.	0.00% 0/25 • 2 years 4 months Study treatment was administered for up to 2 years. Adverse events were accessed through 90 days after the last dose of study treatment.	0.00% 0/47 • 2 years 4 months Study treatment was administered for up to 2 years. Adverse events were accessed through 90 days after the last dose of study treatment.
Nervous system disorders Neuropathy	0.00% 0/41 • 2 years 4 months Study treatment was administered for up to 2 years. Adverse events were accessed through 90 days after the last dose of study treatment.	0.00% 0/25 • 2 years 4 months Study treatment was administered for up to 2 years. Adverse events were accessed through 90 days after the last dose of study treatment.	2.1% 1/47 • Number of events 1 • 2 years 4 months Study treatment was administered for up to 2 years. Adverse events were accessed through 90 days after the last dose of study treatment.
Infections and infestations Cellulitis	2.4% 1/41 • Number of events 1 • 2 years 4 months Study treatment was administered for up to 2 years. Adverse events were accessed through 90 days after the last dose of study treatment.	0.00% 0/25 • 2 years 4 months Study treatment was administered for up to 2 years. Adverse events were accessed through 90 days after the last dose of study treatment.	0.00% 0/47 • 2 years 4 months Study treatment was administered for up to 2 years. Adverse events were accessed through 90 days after the last dose of study treatment.
Hepatobiliary disorders Alanine aminotransferase Increased (ALT)	0.00% 0/41 • 2 years 4 months Study treatment was administered for up to 2 years. Adverse events were accessed through 90 days after the last dose of study treatment.	0.00% 0/25 • 2 years 4 months Study treatment was administered for up to 2 years. Adverse events were accessed through 90 days after the last dose of study treatment.	2.1% 1/47 • Number of events 1 • 2 years 4 months Study treatment was administered for up to 2 years. Adverse events were accessed through 90 days after the last dose of study treatment.
Hepatobiliary disorders Aspartate aminotransferase increased (AST)	0.00% 0/41 • 2 years 4 months Study treatment was administered for up to 2 years. Adverse events were accessed through 90 days after the last dose of study treatment.	0.00% 0/25 • 2 years 4 months Study treatment was administered for up to 2 years. Adverse events were accessed through 90 days after the last dose of study treatment.	2.1% 1/47 • Number of events 1 • 2 years 4 months Study treatment was administered for up to 2 years. Adverse events were accessed through 90 days after the last dose of study treatment.
Hepatobiliary disorders Alkaline Phosphate elevated	0.00% 0/41 • 2 years 4 months Study treatment was administered for up to 2 years. Adverse events were accessed through 90 days after the last dose of study treatment.	0.00% 0/25 • 2 years 4 months Study treatment was administered for up to 2 years. Adverse events were accessed through 90 days after the last dose of study treatment.	2.1% 1/47 • Number of events 1 • 2 years 4 months Study treatment was administered for up to 2 years. Adverse events were accessed through 90 days after the last dose of study treatment.
Blood and lymphatic system disorders hemolytic anemia	0.00% 0/41 • 2 years 4 months Study treatment was administered for up to 2 years. Adverse events were accessed through 90 days after the last dose of study treatment.	0.00% 0/25 • 2 years 4 months Study treatment was administered for up to 2 years. Adverse events were accessed through 90 days after the last dose of study treatment.	2.1% 1/47 • Number of events 1 • 2 years 4 months Study treatment was administered for up to 2 years. Adverse events were accessed through 90 days after the last dose of study treatment.

Other adverse events

Measure	Cohort A: MSI Positive Colorectal Cancer n=41 participants at risk MK-3475: MK-3475 10 mg/kg every 14 days	Cohort B: MSI Negative Colorectal Cancer n=25 participants at risk MK-3475: MK-3475 10 mg/kg every 14 days	Cohort C: MSI Positive Non-Colorectal Cancer n=47 participants at risk MK-3475: MK-3475 10 mg/kg every 14 days
Blood and lymphatic system disorders Anemia	7.3% 3/41 • Number of events 3 • 2 years 4 months Study treatment was administered for up to 2 years. Adverse events were accessed through 90 days after the last dose of study treatment.	0.00% 0/25 • 2 years 4 months Study treatment was administered for up to 2 years. Adverse events were accessed through 90 days after the last dose of study treatment.	8.5% 4/47 • Number of events 4 • 2 years 4 months Study treatment was administered for up to 2 years. Adverse events were accessed through 90 days after the last dose of study treatment.
Endocrine disorders Hypothyroidism/thyroiditis	14.6% 6/41 • Number of events 6 • 2 years 4 months Study treatment was administered for up to 2 years. Adverse events were accessed through 90 days after the last dose of study treatment.	0.00% 0/25 • 2 years 4 months Study treatment was administered for up to 2 years. Adverse events were accessed through 90 days after the last dose of study treatment.	27.7% 13/47 • Number of events 13 • 2 years 4 months Study treatment was administered for up to 2 years. Adverse events were accessed through 90 days after the last dose of study treatment.
Gastrointestinal disorders Diarrhea	24.4% 10/41 • Number of events 10 • 2 years 4 months Study treatment was administered for up to 2 years. Adverse events were accessed through 90 days after the last dose of study treatment.	0.00% 0/25 • 2 years 4 months Study treatment was administered for up to 2 years. Adverse events were accessed through 90 days after the last dose of study treatment.	19.1% 9/47 • Number of events 9 • 2 years 4 months Study treatment was administered for up to 2 years. Adverse events were accessed through 90 days after the last dose of study treatment.
Gastrointestinal disorders Nausea	12.2% 5/41 • Number of events 5 • 2 years 4 months Study treatment was administered for up to 2 years. Adverse events were accessed through 90 days after the last dose of study treatment.	0.00% 0/25 • 2 years 4 months Study treatment was administered for up to 2 years. Adverse events were accessed through 90 days after the last dose of study treatment.	17.0% 8/47 • Number of events 8 • 2 years 4 months Study treatment was administered for up to 2 years. Adverse events were accessed through 90 days after the last dose of study treatment.
General disorders Fatigue	19.5% 8/41 • Number of events 8 • 2 years 4 months Study treatment was administered for up to 2 years. Adverse events were accessed through 90 days after the last dose of study treatment.	4.0% 1/25 • Number of events 1 • 2 years 4 months Study treatment was administered for up to 2 years. Adverse events were accessed through 90 days after the last dose of study treatment.	27.7% 13/47 • Number of events 13 • 2 years 4 months Study treatment was administered for up to 2 years. Adverse events were accessed through 90 days after the last dose of study treatment.
Investigations Alanine aminotransferase Increased (ALT)	7.3% 3/41 • Number of events 3 • 2 years 4 months Study treatment was administered for up to 2 years. Adverse events were accessed through 90 days after the last dose of study treatment.	0.00% 0/25 • 2 years 4 months Study treatment was administered for up to 2 years. Adverse events were accessed through 90 days after the last dose of study treatment.	6.4% 3/47 • Number of events 3 • 2 years 4 months Study treatment was administered for up to 2 years. Adverse events were accessed through 90 days after the last dose of study treatment.
Investigations Aspartate aminotransferase increased (AST)	9.8% 4/41 • Number of events 4 • 2 years 4 months Study treatment was administered for up to 2 years. Adverse events were accessed through 90 days after the last dose of study treatment.	0.00% 0/25 • 2 years 4 months Study treatment was administered for up to 2 years. Adverse events were accessed through 90 days after the last dose of study treatment.	10.6% 5/47 • Number of events 5 • 2 years 4 months Study treatment was administered for up to 2 years. Adverse events were accessed through 90 days after the last dose of study treatment.
Investigations Lymphocyte count decreased	4.9% 2/41 • Number of events 2 • 2 years 4 months Study treatment was administered for up to 2 years. Adverse events were accessed through 90 days after the last dose of study treatment.	0.00% 0/25 • 2 years 4 months Study treatment was administered for up to 2 years. Adverse events were accessed through 90 days after the last dose of study treatment.	10.6% 5/47 • Number of events 5 • 2 years 4 months Study treatment was administered for up to 2 years. Adverse events were accessed through 90 days after the last dose of study treatment.
Investigations White blood cell decreased	7.3% 3/41 • Number of events 3 • 2 years 4 months Study treatment was administered for up to 2 years. Adverse events were accessed through 90 days after the last dose of study treatment.	0.00% 0/25 • 2 years 4 months Study treatment was administered for up to 2 years. Adverse events were accessed through 90 days after the last dose of study treatment.	6.4% 3/47 • Number of events 3 • 2 years 4 months Study treatment was administered for up to 2 years. Adverse events were accessed through 90 days after the last dose of study treatment.
Musculoskeletal and connective tissue disorders Arthralgia	17.1% 7/41 • Number of events 7 • 2 years 4 months Study treatment was administered for up to 2 years. Adverse events were accessed through 90 days after the last dose of study treatment.	0.00% 0/25 • 2 years 4 months Study treatment was administered for up to 2 years. Adverse events were accessed through 90 days after the last dose of study treatment.	8.5% 4/47 • Number of events 4 • 2 years 4 months Study treatment was administered for up to 2 years. Adverse events were accessed through 90 days after the last dose of study treatment.
Nervous system disorders Neuropathy	2.4% 1/41 • Number of events 1 • 2 years 4 months Study treatment was administered for up to 2 years. Adverse events were accessed through 90 days after the last dose of study treatment.	0.00% 0/25 • 2 years 4 months Study treatment was administered for up to 2 years. Adverse events were accessed through 90 days after the last dose of study treatment.	10.6% 5/47 • Number of events 5 • 2 years 4 months Study treatment was administered for up to 2 years. Adverse events were accessed through 90 days after the last dose of study treatment.
Skin and subcutaneous tissue disorders Pruritus	14.6% 6/41 • Number of events 6 • 2 years 4 months Study treatment was administered for up to 2 years. Adverse events were accessed through 90 days after the last dose of study treatment.	0.00% 0/25 • 2 years 4 months Study treatment was administered for up to 2 years. Adverse events were accessed through 90 days after the last dose of study treatment.	27.7% 13/47 • Number of events 13 • 2 years 4 months Study treatment was administered for up to 2 years. Adverse events were accessed through 90 days after the last dose of study treatment.
Skin and subcutaneous tissue disorders Rash	24.4% 10/41 • Number of events 10 • 2 years 4 months Study treatment was administered for up to 2 years. Adverse events were accessed through 90 days after the last dose of study treatment.	8.0% 2/25 • Number of events 2 • 2 years 4 months Study treatment was administered for up to 2 years. Adverse events were accessed through 90 days after the last dose of study treatment.	31.9% 15/47 • Number of events 15 • 2 years 4 months Study treatment was administered for up to 2 years. Adverse events were accessed through 90 days after the last dose of study treatment.

Additional Information

Dung Le, MD

The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Phone: 443-287-0002

Email: dle@jhmi.edu

Results disclosure agreements

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