Trial Outcomes & Findings for Study of MK-8353 + Selumetinib in Advanced/Metastatic Solid Tumors (MK-8353-014) (NCT NCT03745989)

Last Updated: 2023-07-27

Results Overview

A dose limiting toxicity (DLT) is defined as any hematologic or non-hematologic toxicity ≥Grade 3 per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. The occurrence of any of the designated toxicities during Cycle 1 (3-week cycle) were considered a DLT, if assessed by the investigator to be possibly, probably, or definitely related to study treatment administration. The number of participants experiencing DLTs was assessed.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

30 participants

Primary outcome timeframe

Cycle 1 (3-week Cycle) (Up to 3 weeks)

Results posted on

2023-07-27

Participant Flow

Participant milestones

Participant milestones
Measure	MK-8353 50 mg + Selumetinib 25 mg Participants received 50 mg twice daily (BID) of MK-8353 and 25 mg selumetinib orally with 4 days on and 3 days off until disease progression or discontinuation.	MK-8353 100 mg + Selumetinib 50 mg Participants received 100 mg BID of MK-8353 and 50 mg selumetinib orally with 4 days on and 3 days off until disease progression or discontinuation.	MK-8353 150 mg + Selumetinib 75 mg Participants received 150 mg BID of MK-8353 and 75 mg selumetinib orally with 4 days on and 3 days off until disease progression or discontinuation.
Overall Study STARTED	3	12	15
Overall Study COMPLETED	0	0	0
Overall Study NOT COMPLETED	3	12	15

Reasons for withdrawal

Reasons for withdrawal
Measure	MK-8353 50 mg + Selumetinib 25 mg Participants received 50 mg twice daily (BID) of MK-8353 and 25 mg selumetinib orally with 4 days on and 3 days off until disease progression or discontinuation.	MK-8353 100 mg + Selumetinib 50 mg Participants received 100 mg BID of MK-8353 and 50 mg selumetinib orally with 4 days on and 3 days off until disease progression or discontinuation.	MK-8353 150 mg + Selumetinib 75 mg Participants received 150 mg BID of MK-8353 and 75 mg selumetinib orally with 4 days on and 3 days off until disease progression or discontinuation.
Overall Study Death	3	7	4
Overall Study Lost to Follow-up	0	2	0
Overall Study Sponsor Decision	0	2	8
Overall Study Withdrawal by Subject	0	1	3

Baseline Characteristics

Study of MK-8353 + Selumetinib in Advanced/Metastatic Solid Tumors (MK-8353-014)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	MK-8353 50 mg + Selumetinib 25 mg n=3 Participants Participants received 50 mg twice daily (BID) of MK-8353 and 25 mg selumetinib orally with 4 days on and 3 days off until disease progression or discontinuation.	MK-8353 100 mg + Selumetinib 50 mg n=12 Participants Participants received 100 mg BID of MK-8353 and 50 mg selumetinib orally with 4 days on and 3 days off until disease progression or discontinuation.	MK-8353 150 mg + Selumetinib 75 mg n=15 Participants Participants received 150 mg BID of MK-8353 and 75 mg selumetinib orally with 4 days on and 3 days off until disease progression or discontinuation.	Total n=30 Participants Total of all reporting groups
Age, Continuous	57.0 Years STANDARD_DEVIATION 8.2 • n=5 Participants	58.6 Years STANDARD_DEVIATION 13.3 • n=7 Participants	60.2 Years STANDARD_DEVIATION 16.1 • n=5 Participants	59.2 Years STANDARD_DEVIATION 14.1 • n=4 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	7 Participants n=7 Participants	7 Participants n=5 Participants	14 Participants n=4 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	5 Participants n=7 Participants	8 Participants n=5 Participants	16 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	2 Participants n=5 Participants	12 Participants n=7 Participants	15 Participants n=5 Participants	29 Participants n=4 Participants
Ethnicity (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
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	1 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	3 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	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) White	2 Participants n=5 Participants	11 Participants n=7 Participants	13 Participants n=5 Participants	26 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	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants

PRIMARY outcome

Timeframe: Cycle 1 (3-week Cycle) (Up to 3 weeks)

Population: The analysis population included all participants who received at least 1 dose of study treatment who met the criteria for DLT evaluability (finished Cycle 1 without a DLT or experienced a DLT in Cycle 1).

Outcome measures

Outcome measures
Measure	MK-8353 50 mg + Selumetinib 25 mg n=3 Participants Participants received 50 mg twice daily (BID) of MK-8353 and 25 mg selumetinib orally with 4 days on and 3 days off until disease progression or discontinuation.	MK-8353 100 mg + Selumetinib 50 mg n=11 Participants Participants received 100 mg BID of MK-8353 and 50 mg selumetinib orally with 4 days on and 3 days off until disease progression or discontinuation.	MK-8353 150 mg + Selumetinib 75 mg n=14 Participants Participants received 150 mg BID of MK-8353 and 75 mg selumetinib orally with 4 days on and 3 days off until disease progression or discontinuation.
Number of Participants Experiencing Dose Limiting Toxicities	0 Participants	1 Participants	7 Participants

PRIMARY outcome

Timeframe: ~90 days after last treatment dose (up to ~45 weeks)

Population: The analysis population included all participants who received at least one dose of study treatment.

An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants experiencing AEs was assessed.

Outcome measures

Outcome measures
Measure	MK-8353 50 mg + Selumetinib 25 mg n=3 Participants Participants received 50 mg twice daily (BID) of MK-8353 and 25 mg selumetinib orally with 4 days on and 3 days off until disease progression or discontinuation.	MK-8353 100 mg + Selumetinib 50 mg n=12 Participants Participants received 100 mg BID of MK-8353 and 50 mg selumetinib orally with 4 days on and 3 days off until disease progression or discontinuation.	MK-8353 150 mg + Selumetinib 75 mg n=15 Participants Participants received 150 mg BID of MK-8353 and 75 mg selumetinib orally with 4 days on and 3 days off until disease progression or discontinuation.
Number of Participants Experiencing Adverse Events	3 Participants	12 Participants	15 Participants

PRIMARY outcome

Timeframe: Up to ~33 weeks

Population: The analysis population included all participants who received at least one dose of study treatment.

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants discontinuing study treatment due to AEs was assessed.

Outcome measures

Outcome measures
Measure	MK-8353 50 mg + Selumetinib 25 mg n=3 Participants Participants received 50 mg twice daily (BID) of MK-8353 and 25 mg selumetinib orally with 4 days on and 3 days off until disease progression or discontinuation.	MK-8353 100 mg + Selumetinib 50 mg n=12 Participants Participants received 100 mg BID of MK-8353 and 50 mg selumetinib orally with 4 days on and 3 days off until disease progression or discontinuation.	MK-8353 150 mg + Selumetinib 75 mg n=15 Participants Participants received 150 mg BID of MK-8353 and 75 mg selumetinib orally with 4 days on and 3 days off until disease progression or discontinuation.
Number of Participants Discontinuing Study Treatment Due to AEs	0 Participants	3 Participants	1 Participants

SECONDARY outcome

Timeframe: Study Days 1 and 4 of Cycle 1 (3-week cycle) at pre-dose and at 1, 2, 4, 6 hours, and between 8 and 12 hours post-dose

Population: The analysis population included all participants who were compliant with the study procedures and had available MK-8353 AUC data from at least 1 treatment.

Blood samples were collected to determine the area under the curve from time 0 to 12 hours (AUC0-12). AUC is a measure of the amount of drug in the blood over time.

Outcome measures

Outcome measures
Measure	MK-8353 50 mg + Selumetinib 25 mg n=2 Participants Participants received 50 mg twice daily (BID) of MK-8353 and 25 mg selumetinib orally with 4 days on and 3 days off until disease progression or discontinuation.	MK-8353 100 mg + Selumetinib 50 mg n=9 Participants Participants received 100 mg BID of MK-8353 and 50 mg selumetinib orally with 4 days on and 3 days off until disease progression or discontinuation.	MK-8353 150 mg + Selumetinib 75 mg n=10 Participants Participants received 150 mg BID of MK-8353 and 75 mg selumetinib orally with 4 days on and 3 days off until disease progression or discontinuation.
Area Under the Plasma Concentration-Time Curve for MK-8353 From Time 0 to 12 Hours MK-8353, Cycle 1, Day 1	14.3 hr*μmol/liter Geometric Coefficient of Variation 62.7	9.66 hr*μmol/liter Geometric Coefficient of Variation 50.7	13.7 hr*μmol/liter Geometric Coefficient of Variation 32.8
Area Under the Plasma Concentration-Time Curve for MK-8353 From Time 0 to 12 Hours MK-8353, Cycle 1, Day 4	16.7 hr*μmol/liter Geometric Coefficient of Variation 365.7	19.0 hr*μmol/liter Geometric Coefficient of Variation 36.9	20.9 hr*μmol/liter Geometric Coefficient of Variation 60.6

SECONDARY outcome

Timeframe: Study Days 1 and 4 of Cycle 1 (3-week cycle) at pre-dose and at 1, 2, 4, 6 hours, and between 8 and 12 hours post-dose

Population: The analysis population included all participants who were compliant with the study procedures and had available selumetinib AUC data from at least 1 treatment.

Blood samples were collected to determine the AUC0-12. AUC is a measure of the amount of drug in the blood over time.

Outcome measures

Outcome measures
Measure	MK-8353 50 mg + Selumetinib 25 mg n=3 Participants Participants received 50 mg twice daily (BID) of MK-8353 and 25 mg selumetinib orally with 4 days on and 3 days off until disease progression or discontinuation.	MK-8353 100 mg + Selumetinib 50 mg n=12 Participants Participants received 100 mg BID of MK-8353 and 50 mg selumetinib orally with 4 days on and 3 days off until disease progression or discontinuation.	MK-8353 150 mg + Selumetinib 75 mg n=12 Participants Participants received 150 mg BID of MK-8353 and 75 mg selumetinib orally with 4 days on and 3 days off until disease progression or discontinuation.
AUC0-12 for Selumetinib Selumetinib, Cycle 1, Day 1	2.99 hr*μmol/liter Geometric Coefficient of Variation 27.2	5.20 hr*μmol/liter Geometric Coefficient of Variation 63.2	10.9 hr*μmol/liter Geometric Coefficient of Variation 49.1
AUC0-12 for Selumetinib Selumetinib, Cycle 1, Day 4	3.80 hr*μmol/liter Geometric Coefficient of Variation 24.6	6.28 hr*μmol/liter Geometric Coefficient of Variation 75.3	12.7 hr*μmol/liter Geometric Coefficient of Variation 31.5

SECONDARY outcome

Timeframe: Study Days 1 and 4 of Cycles 1 and 2 (3-week cycles). For Cycle 1, pre-dose and at 1, 2, 4, 6 hours, and between 8 and 12 hours post-dose; and for Cycle 2 pre-dose, and at 1 and 4 hours post-dose

Population: The analysis population included all participants who were compliant with the study procedures and had available MK-8353 Cmin data from at least 1 treatment.

Blood samples were collected to determine the minimum observed plasma concentration (Cmin) which is the minimum amount of drug in the plasma after the dose is given. In cases where Cmin values were below the limit of quantification (BLOQ), arithmetic mean (percent coefficient of variation \[%CV\]) was reported instead of geometric mean (percent geometric coefficient of variation \[%GCV\]), since geometric mean (%GCV) was not calculable. In cases where all Cmin values were BLOQ, mean was not calculable and indicated as "NA."

Outcome measures

Outcome measures
Measure	MK-8353 50 mg + Selumetinib 25 mg n=3 Participants Participants received 50 mg twice daily (BID) of MK-8353 and 25 mg selumetinib orally with 4 days on and 3 days off until disease progression or discontinuation.	MK-8353 100 mg + Selumetinib 50 mg n=10 Participants Participants received 100 mg BID of MK-8353 and 50 mg selumetinib orally with 4 days on and 3 days off until disease progression or discontinuation.	MK-8353 150 mg + Selumetinib 75 mg n=13 Participants Participants received 150 mg BID of MK-8353 and 75 mg selumetinib orally with 4 days on and 3 days off until disease progression or discontinuation.
Minimum Observed Plasma Concentration for MK-8353 MK-8353, Cycle 1, Day 1	NA μmol/liter Geometric Coefficient of Variation NA NA=All Cmin values of MK-8353 plasma concentrations were BLOQ at Cycle 1 Day 1 and Geometric Mean (%GCV) was not calculable.	NA μmol/liter Geometric Coefficient of Variation NA NA=All Cmin values of MK-8353 plasma concentrations were BLOQ at Cycle 1 Day 1 and Geometric Mean (%GCV) was not calculable.	NA μmol/liter Geometric Coefficient of Variation NA NA=All Cmin values of MK-8353 plasma concentrations were BLOQ at Cycle 1 Day 1 and Geometric Mean (%GCV) was not calculable.
Minimum Observed Plasma Concentration for MK-8353 MK-8353, Cycle 1 Day 4	0.695 μmol/liter Geometric Coefficient of Variation 222.6	1.10 μmol/liter Geometric Coefficient of Variation 50.6	1.47 μmol/liter Geometric Coefficient of Variation 455.5
Minimum Observed Plasma Concentration for MK-8353 MK-8353, Cycle 2 Day 1	0.0361 μmol/liter Geometric Coefficient of Variation 173.2	0.0313 μmol/liter Geometric Coefficient of Variation 191.0	0.0166 μmol/liter Geometric Coefficient of Variation 189.7
Minimum Observed Plasma Concentration for MK-8353 MK-8353, Cycle 2 Day 4	0.598 μmol/liter Geometric Coefficient of Variation 172.6	0.995 μmol/liter Geometric Coefficient of Variation 90.7	1.47 μmol/liter Geometric Coefficient of Variation 84.8

SECONDARY outcome

Population: The analysis population included all participants who were compliant with the study procedures and had available selumetinib Cmin data from at least 1 treatment.

Blood samples were collected to determine the Cmin which is the minimum amount of drug in the plasma after the dose is given. In cases where Cmin values were BLOQ, arithmetic mean (%CV) was reported instead of geometric mean (%GCV), since geometric mean (%GCV) was not calculable. In cases where all Cmin values were BLOQ, mean was not calculable and indicated as "NA."

Outcome measures

Outcome measures
Measure	MK-8353 50 mg + Selumetinib 25 mg n=3 Participants Participants received 50 mg twice daily (BID) of MK-8353 and 25 mg selumetinib orally with 4 days on and 3 days off until disease progression or discontinuation.	MK-8353 100 mg + Selumetinib 50 mg n=10 Participants Participants received 100 mg BID of MK-8353 and 50 mg selumetinib orally with 4 days on and 3 days off until disease progression or discontinuation.	MK-8353 150 mg + Selumetinib 75 mg n=11 Participants Participants received 150 mg BID of MK-8353 and 75 mg selumetinib orally with 4 days on and 3 days off until disease progression or discontinuation.
Cmin for Selumetinib Selumetinib, Cycle 1, Day 1	NA μmol/liter Geometric Coefficient of Variation NA NA=All Cmin values of Selumetinib plasma concentrations were BLOQ at Cycle 1 Day 1 and Geometric Mean (%GCV) was not calculable.	NA μmol/liter Geometric Coefficient of Variation NA NA=All Cmin values of Selumetinib plasma concentrations were BLOQ at Cycle 1 Day 1 and Geometric Mean (%GCV) was not calculable.	NA μmol/liter Geometric Coefficient of Variation NA NA=All Cmin values of Selumetinib plasma concentrations were BLOQ at Cycle 1 Day 1 and Geometric Mean (%GCV) was not calculable.
Cmin for Selumetinib Selumetinib, Cycle 1, Day 4	0.101 μmol/liter Geometric Coefficient of Variation 35.1	0.265 μmol/liter Geometric Coefficient of Variation 38.9	0.456 μmol/liter Geometric Coefficient of Variation 160.1
Cmin for Selumetinib Selumetinib, Cycle 2, Day 1	NA μmol/liter Geometric Coefficient of Variation NA NA=All Cmin values of Selumetinib plasma concentrations were BLOQ at Cycle 2 Day 1 and Geometric Mean (%GCV) was not calculable.	0.00202 μmol/liter Geometric Coefficient of Variation 232.9	0.00124 μmol/liter Geometric Coefficient of Variation 215.7
Cmin for Selumetinib Selumetinib, Cycle 2, Day 4	0.127 μmol/liter Geometric Coefficient of Variation 74.6	0.174 μmol/liter Geometric Coefficient of Variation 80.3	0.257 μmol/liter Geometric Coefficient of Variation 47.5

SECONDARY outcome

Timeframe: Study Days 1 and 4 of Cycle 1 (3-week cycle) at pre-dose and at 1, 2, 4, 6 hours, and between 8 and 12 hours post-dose

Population: The analysis population included all participants who were compliant with the study procedures and had available MK-8353 Cmax data from at least 1 treatment.

Blood samples were collected to determine the maximum observed plasma concentration (Cmax) which is the measure of the maximum amount of drug in the plasma after the dose is given.

Outcome measures

Outcome measures
Measure	MK-8353 50 mg + Selumetinib 25 mg n=3 Participants Participants received 50 mg twice daily (BID) of MK-8353 and 25 mg selumetinib orally with 4 days on and 3 days off until disease progression or discontinuation.	MK-8353 100 mg + Selumetinib 50 mg n=12 Participants Participants received 100 mg BID of MK-8353 and 50 mg selumetinib orally with 4 days on and 3 days off until disease progression or discontinuation.	MK-8353 150 mg + Selumetinib 75 mg n=15 Participants Participants received 150 mg BID of MK-8353 and 75 mg selumetinib orally with 4 days on and 3 days off until disease progression or discontinuation.
Maximum Observed Plasma Concentration for MK-8353 MK-8353, Cycle 1, Day 1	1.24 μmol/liter Geometric Coefficient of Variation 138.4	1.65 μmol/liter Geometric Coefficient of Variation 60.9	2.95 μmol/liter Geometric Coefficient of Variation 62.3
Maximum Observed Plasma Concentration for MK-8353 MK-8353, Cycle 1, Day 4	1.87 μmol/liter Geometric Coefficient of Variation 149.4	2.53 μmol/liter Geometric Coefficient of Variation 51.5	3.61 μmol/liter Geometric Coefficient of Variation 80.9

SECONDARY outcome

Timeframe: Study Days 1 and 4 of Cycle 1 (3-week cycle) at pre-dose and at 1, 2, 4, 6 hours, and between 8 and 12 hours post-dose

Population: The analysis population included all participants who were compliant with the study procedures and had available selumetinib Cmax data from at least 1 treatment.

Blood samples were collected to determine the Cmax which is the measure of the maximum amount of drug in the plasma after the dose is given.

Outcome measures

Outcome measures
Measure	MK-8353 50 mg + Selumetinib 25 mg n=3 Participants Participants received 50 mg twice daily (BID) of MK-8353 and 25 mg selumetinib orally with 4 days on and 3 days off until disease progression or discontinuation.	MK-8353 100 mg + Selumetinib 50 mg n=12 Participants Participants received 100 mg BID of MK-8353 and 50 mg selumetinib orally with 4 days on and 3 days off until disease progression or discontinuation.	MK-8353 150 mg + Selumetinib 75 mg n=13 Participants Participants received 150 mg BID of MK-8353 and 75 mg selumetinib orally with 4 days on and 3 days off until disease progression or discontinuation.
Cmax for Selumetinib Selumetinib, Cycle 1,Day 1	1.01 μmol/liter Geometric Coefficient of Variation 29.7	1.96 μmol/liter Geometric Coefficient of Variation 91.1	3.37 μmol/liter Geometric Coefficient of Variation 57.1
Cmax for Selumetinib Selumetinib, Cycle 1, Day 4	1.04 μmol/liter Geometric Coefficient of Variation 13.3	1.44 μmol/liter Geometric Coefficient of Variation 123.6	2.37 μmol/liter Geometric Coefficient of Variation 107.5

Adverse Events

MK-8353 50 mg + Selumetinib 25 mg

Serious events: 0 serious events

Other events: 3 other events

Deaths: 3 deaths

MK-8353 100 mg + Selumetinib 50 mg

Serious events: 3 serious events

Other events: 11 other events

Deaths: 8 deaths

MK-8353 150 mg + Selumetinib 75 mg

Serious events: 4 serious events

Other events: 15 other events

Deaths: 6 deaths

Serious adverse events

Serious adverse events
Measure	MK-8353 50 mg + Selumetinib 25 mg n=3 participants at risk Participants received 50 mg twice daily (BID) of MK-8353 and 25 mg selumetinib orally with 4 days on and 3 days off until disease progression or discontinuation.	MK-8353 100 mg + Selumetinib 50 mg n=12 participants at risk Participants received 100 mg BID of MK-8353 and 50 mg selumetinib orally with 4 days on and 3 days off until disease progression or discontinuation.	MK-8353 150 mg + Selumetinib 75 mg n=15 participants at risk Participants received 150 mg BID of MK-8353 and 75 mg selumetinib orally with 4 days on and 3 days off until disease progression or discontinuation.
Blood and lymphatic system disorders Anaemia	0.00% 0/3 • Non-serious adverse events (NSAEs): Up to ~45 weeks; Serious adverse events (SAEs): Up to ~45 weeks. All-cause mortality: Up to 24 months NSAE, SAE, and all-cause mortality tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer was not considered an AE unless considered related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	8.3% 1/12 • Number of events 2 • Non-serious adverse events (NSAEs): Up to ~45 weeks; Serious adverse events (SAEs): Up to ~45 weeks. All-cause mortality: Up to 24 months NSAE, SAE, and all-cause mortality tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer was not considered an AE unless considered related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	0.00% 0/15 • Non-serious adverse events (NSAEs): Up to ~45 weeks; Serious adverse events (SAEs): Up to ~45 weeks. All-cause mortality: Up to 24 months NSAE, SAE, and all-cause mortality tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer was not considered an AE unless considered related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Gastrointestinal disorders Ascites	0.00% 0/3 • Non-serious adverse events (NSAEs): Up to ~45 weeks; Serious adverse events (SAEs): Up to ~45 weeks. All-cause mortality: Up to 24 months NSAE, SAE, and all-cause mortality tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer was not considered an AE unless considered related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	8.3% 1/12 • Number of events 1 • Non-serious adverse events (NSAEs): Up to ~45 weeks; Serious adverse events (SAEs): Up to ~45 weeks. All-cause mortality: Up to 24 months NSAE, SAE, and all-cause mortality tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer was not considered an AE unless considered related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	0.00% 0/15 • Non-serious adverse events (NSAEs): Up to ~45 weeks; Serious adverse events (SAEs): Up to ~45 weeks. All-cause mortality: Up to 24 months NSAE, SAE, and all-cause mortality tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer was not considered an AE unless considered related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Gastrointestinal disorders Diarrhoea	0.00% 0/3 • Non-serious adverse events (NSAEs): Up to ~45 weeks; Serious adverse events (SAEs): Up to ~45 weeks. All-cause mortality: Up to 24 months NSAE, SAE, and all-cause mortality tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer was not considered an AE unless considered related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	0.00% 0/12 • Non-serious adverse events (NSAEs): Up to ~45 weeks; Serious adverse events (SAEs): Up to ~45 weeks. All-cause mortality: Up to 24 months NSAE, SAE, and all-cause mortality tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer was not considered an AE unless considered related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	6.7% 1/15 • Number of events 1 • Non-serious adverse events (NSAEs): Up to ~45 weeks; Serious adverse events (SAEs): Up to ~45 weeks. All-cause mortality: Up to 24 months NSAE, SAE, and all-cause mortality tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer was not considered an AE unless considered related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Gastrointestinal disorders Duodenal obstruction	0.00% 0/3 • Non-serious adverse events (NSAEs): Up to ~45 weeks; Serious adverse events (SAEs): Up to ~45 weeks. All-cause mortality: Up to 24 months NSAE, SAE, and all-cause mortality tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer was not considered an AE unless considered related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	0.00% 0/12 • Non-serious adverse events (NSAEs): Up to ~45 weeks; Serious adverse events (SAEs): Up to ~45 weeks. All-cause mortality: Up to 24 months NSAE, SAE, and all-cause mortality tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer was not considered an AE unless considered related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	6.7% 1/15 • Number of events 1 • Non-serious adverse events (NSAEs): Up to ~45 weeks; Serious adverse events (SAEs): Up to ~45 weeks. All-cause mortality: Up to 24 months NSAE, SAE, and all-cause mortality tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer was not considered an AE unless considered related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Gastrointestinal disorders Large intestinal obstruction	0.00% 0/3 • Non-serious adverse events (NSAEs): Up to ~45 weeks; Serious adverse events (SAEs): Up to ~45 weeks. All-cause mortality: Up to 24 months NSAE, SAE, and all-cause mortality tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer was not considered an AE unless considered related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	0.00% 0/12 • Non-serious adverse events (NSAEs): Up to ~45 weeks; Serious adverse events (SAEs): Up to ~45 weeks. All-cause mortality: Up to 24 months NSAE, SAE, and all-cause mortality tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer was not considered an AE unless considered related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	6.7% 1/15 • Number of events 1 • Non-serious adverse events (NSAEs): Up to ~45 weeks; Serious adverse events (SAEs): Up to ~45 weeks. All-cause mortality: Up to 24 months NSAE, SAE, and all-cause mortality tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer was not considered an AE unless considered related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Gastrointestinal disorders Vomiting	0.00% 0/3 • Non-serious adverse events (NSAEs): Up to ~45 weeks; Serious adverse events (SAEs): Up to ~45 weeks. All-cause mortality: Up to 24 months NSAE, SAE, and all-cause mortality tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer was not considered an AE unless considered related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	0.00% 0/12 • Non-serious adverse events (NSAEs): Up to ~45 weeks; Serious adverse events (SAEs): Up to ~45 weeks. All-cause mortality: Up to 24 months NSAE, SAE, and all-cause mortality tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer was not considered an AE unless considered related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	13.3% 2/15 • Number of events 2 • Non-serious adverse events (NSAEs): Up to ~45 weeks; Serious adverse events (SAEs): Up to ~45 weeks. All-cause mortality: Up to 24 months NSAE, SAE, and all-cause mortality tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer was not considered an AE unless considered related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Infections and infestations Abdominal infection	0.00% 0/3 • Non-serious adverse events (NSAEs): Up to ~45 weeks; Serious adverse events (SAEs): Up to ~45 weeks. All-cause mortality: Up to 24 months NSAE, SAE, and all-cause mortality tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer was not considered an AE unless considered related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	0.00% 0/12 • Non-serious adverse events (NSAEs): Up to ~45 weeks; Serious adverse events (SAEs): Up to ~45 weeks. All-cause mortality: Up to 24 months NSAE, SAE, and all-cause mortality tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer was not considered an AE unless considered related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	6.7% 1/15 • Number of events 1 • Non-serious adverse events (NSAEs): Up to ~45 weeks; Serious adverse events (SAEs): Up to ~45 weeks. All-cause mortality: Up to 24 months NSAE, SAE, and all-cause mortality tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer was not considered an AE unless considered related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Infections and infestations Pneumonia	0.00% 0/3 • Non-serious adverse events (NSAEs): Up to ~45 weeks; Serious adverse events (SAEs): Up to ~45 weeks. All-cause mortality: Up to 24 months NSAE, SAE, and all-cause mortality tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer was not considered an AE unless considered related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	8.3% 1/12 • Number of events 1 • Non-serious adverse events (NSAEs): Up to ~45 weeks; Serious adverse events (SAEs): Up to ~45 weeks. All-cause mortality: Up to 24 months NSAE, SAE, and all-cause mortality tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer was not considered an AE unless considered related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	13.3% 2/15 • Number of events 2 • Non-serious adverse events (NSAEs): Up to ~45 weeks; Serious adverse events (SAEs): Up to ~45 weeks. All-cause mortality: Up to 24 months NSAE, SAE, and all-cause mortality tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer was not considered an AE unless considered related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Infections and infestations Sepsis	0.00% 0/3 • Non-serious adverse events (NSAEs): Up to ~45 weeks; Serious adverse events (SAEs): Up to ~45 weeks. All-cause mortality: Up to 24 months NSAE, SAE, and all-cause mortality tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer was not considered an AE unless considered related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	0.00% 0/12 • Non-serious adverse events (NSAEs): Up to ~45 weeks; Serious adverse events (SAEs): Up to ~45 weeks. All-cause mortality: Up to 24 months NSAE, SAE, and all-cause mortality tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer was not considered an AE unless considered related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	6.7% 1/15 • Number of events 1 • Non-serious adverse events (NSAEs): Up to ~45 weeks; Serious adverse events (SAEs): Up to ~45 weeks. All-cause mortality: Up to 24 months NSAE, SAE, and all-cause mortality tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer was not considered an AE unless considered related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/3 • Non-serious adverse events (NSAEs): Up to ~45 weeks; Serious adverse events (SAEs): Up to ~45 weeks. All-cause mortality: Up to 24 months NSAE, SAE, and all-cause mortality tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer was not considered an AE unless considered related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	0.00% 0/12 • Non-serious adverse events (NSAEs): Up to ~45 weeks; Serious adverse events (SAEs): Up to ~45 weeks. All-cause mortality: Up to 24 months NSAE, SAE, and all-cause mortality tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer was not considered an AE unless considered related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	6.7% 1/15 • Number of events 1 • Non-serious adverse events (NSAEs): Up to ~45 weeks; Serious adverse events (SAEs): Up to ~45 weeks. All-cause mortality: Up to 24 months NSAE, SAE, and all-cause mortality tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer was not considered an AE unless considered related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Respiratory, thoracic and mediastinal disorders Pneumonia aspiration	0.00% 0/3 • Non-serious adverse events (NSAEs): Up to ~45 weeks; Serious adverse events (SAEs): Up to ~45 weeks. All-cause mortality: Up to 24 months NSAE, SAE, and all-cause mortality tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer was not considered an AE unless considered related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	8.3% 1/12 • Number of events 1 • Non-serious adverse events (NSAEs): Up to ~45 weeks; Serious adverse events (SAEs): Up to ~45 weeks. All-cause mortality: Up to 24 months NSAE, SAE, and all-cause mortality tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer was not considered an AE unless considered related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	0.00% 0/15 • Non-serious adverse events (NSAEs): Up to ~45 weeks; Serious adverse events (SAEs): Up to ~45 weeks. All-cause mortality: Up to 24 months NSAE, SAE, and all-cause mortality tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer was not considered an AE unless considered related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.

Other adverse events

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp.

Phone: 1-800-672-6372

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee If publication activity is not directed by the Sponsor, the investigator agrees to submit all manuscripts or abstracts to the Sponsor before submission. This allows the Sponsor to protect proprietary information and to provide comments. Authorship will be determined by mutual agreement and in line with International Committee of Medical Journal Editors authorship requirements.
Publication restrictions are in place

Restriction type: OTHER