Study of MK-8353 in Combination With Pembrolizumab (MK-3475) in Participants With Advanced Malignancies (MK-8353-013)

A Phase Ib Study to Evaluate the Safety and Tolerability of MK-8353 in Combination With Pembrolizumab in Patients With Advanced Malignancies

Status

Terminated

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02972034

Enrollment

111

Registered

2016-11-23

Start date

2017-01-13

Completion date

2022-12-02

Last updated

2024-11-21

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Colorectal Cancer, Neoplasms

Brief summary

This study will evaluate the safety, tolerability and preliminary efficacy of MK-8353 when administered in combination with pembrolizumab (MK-3475). There are two parts in this study: Part 1 will be dose escalation and confirmation, and Part 2 will be a cohort expansion. In Part 1, the recommended phase II dose (RP2D) of MK-8353 in combination with a fixed dose of pembrolizumab in participants with advanced malignancies will be identified and confirmed. Participants will be initially enrolled to receive MK-8353 at 350 mg twice a day (BID) in combination with pembrolizumab at a fixed dose of 200 mg on Day 1 of each 3-week cycle (Q3W) for up to 24 months of treatment. In Part 2, participants with advanced colorectal cancer (CRC) that is microsatellite stable (i.e., non-microsatellite instability-high/deficient mismatch repair \[non-MSI-H/dMMR\]) who received at least one and up to five prior lines of therapy will be enrolled at the RP2D in the expansion cohort to further evaluate safety and efficacy.

Interventions

DRUGMK-8353

PO capsule

BIOLOGICALPembrolizumab

IV infusion

Study design

Allocation

NON_RANDOMIZED

Intervention model

SEQUENTIAL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

* Part 1: Has a histologically- or cytologically-documented, locally-advanced or metastatic solid malignancy and has received ≥1 and \<6 prior line of cancer treatment regimen(s). * Part 2: Has a histologically-confirmed adenocarcinoma originating from the colon or rectum (Stage 4 American Joint Committee on Cancer \[AJCC\] 7th edition) that is microsatellite stable (i.e., non-MSI-H/dMMR). Appendiceal cancer is included AND Has experienced disease progression or was intolerant to at least 1 and up to 5 systemic chemotherapy regimen(s) for metastatic CRC that must have included fluroropyrimidines and irinotecan or oxaliplatin, ± anti-vascular endothelial growth factor (VEGF) or anti-epidermal growth factor receptor (EGFR)(if indicated by RAS mutational status). * Provides an archival or newly obtained tumor tissue sample and blood samples for biomarker analysis. * Has ≥1 measurable lesion as defined by RECIST 1.1 on imaging studies. * Has a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale. * Has adequate organ function * Female participants of childbearing potential who are willing to use either 2 adequate barrier methods, or to abstain from heterosexual activity throughout the study. * Male participants of childbearing potential must agree to use an adequate method of contraception.

Exclusion criteria

* Has disease that is suitable for local treatment administered with curative intent. * Part 1: Has received prior therapy with cancer vaccines, or compounds targeting PD-1 (including Merck pembrolizumab \[MK-3475\]), programmed cell death ligand 1 (PD-L1), PD-L2, cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), or Mitogen-activated protein kinase (MAPK)/Extracellular signal-regulated Kinase (MEK). * Part 2: Has received prior therapy with cancer vaccines, or compounds targeting PD-1 (including Merck pembrolizumab \[MK-3475\]), PD-L1, PD-L2, CTLA-4, lymphocyte-activation gene 3 (LAG-3), CD-137, OX-40 (tumor necrosis factor receptor superfamily, member 4 \[TNFRSF4\], also known as CD134), cluster of differentiation 40 (CD-40), glucocorticoid-induced TNFR-related protein (GITR), serine/threonine-protein kinase B-Raf (BRAF), MEK or other molecules in the MAPK pathway. * Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks prior to the first dose of study drug. * Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in doses exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug. * Has had a prior anticancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or has not recovered (i.e. ≤ Grade 1 or at Baseline) from adverse events (AEs) due to agents administered more than 4 weeks earlier. * Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 14 days prior to study Day 1 or who has not recovered (i.e., ≤Grade 1 or at baseline) from AEs due to a previously administered agent. * Has received transfusion of blood products (including platelets or red blood cells) or administration of colony stimulating factors within 4 weeks prior to study Day 1. * Has a known additional malignancy that is progressing or requires active treatment. * Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. * Has active autoimmune disease that has required systemic treatment in past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). * Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis. * Has a history of interstitial lung disease. * Has an active infection requiring systemic therapy. * Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study. * Has a known history of Human Immunodeficiency Virus (HIV). * Has known active Hepatitis B or Hepatitis C. * Has received a live-virus vaccination within 30 days of planned treatment start. * Has had an allogenic tissue/solid organ transplant.

Design outcomes

Primary

Measure	Time frame	Description
Number of Participants Who Experienced an Adverse Event (AE)	Up to 27 months	Number of participants who experienced an AE was defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study therapy and irrespective of causality to study treatment
Number of Participants Who Discontinued Study Drug Due to an Adverse Event (AE)	Up to 24 months	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 who discontinued treatment due to an AE was assessed.
Number of Participants Who Experienced Dose-Limiting Toxicity (DLT)	Cycle 1 (Arms A, B & C: Up to 21 days)	DLT was defined as a treatment-related adverse event (AE) including the following: Grade (Gr) 4 nonhematologic toxicity (not laboratory), Gr 4 hematologic toxicity lasting ≥7 days, except thrombocytopenia or Gr 4 thrombocytopenia of any duration or Gr 3 thrombocytopenia associated with clinically significant bleeding, Gr 3 non-hematological AE with the exception of fatigue lasting \>3 days despite optimal supportive care, any Gr 3 or Gr 4 nonhematologic laboratory value if medical intervention is required to treat the subject, or abnormality leads to hospitalization or abnormality persists for \>1 week, Gr 3 or Gr 4 febrile neutropenia, prolonged delay (\>2 weeks) in initiating Cycle 2 due to treatment-related toxicity, any treatment-related toxicity that causes the subject to discontinue treatment during Cycle 1, missing \>25% of MK-8353 doses as a result of drug-related AE(s) during the first cycle, Gr 5 toxicity.

Secondary

Measure	Time frame	Description
Objective Response Rate (ORR) Based on Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by the Investigator	Up to 24 months	ORR was defined as the percentage of the participants in the analysis population who have a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters). The ORR per RECIST 1.1 as assessed by Investigator was presented.
Percent Change in Carbohydrate Antigen (CA19-9)	Cycle 1-7 Day 1, and end of treatment/ safety follow-up (30 days after the last dose). Each cycle was 21 days.	CA19-9 was the tumour biomarker used to test cancer. Disease progression is indicated by CA19-9 tumor marker elevation
Percent Change in Cancer Antigen 125 (CA-125)	Cycle 1-8 Day 1, and end of treatment/ safety follow-up (30 days after the last dose). Each cycle was 21 days.	CA-125 was the tumour biomarker used to test cancer. Disease progression is indicated by CA-125 tumor marker elevation.
Percent Change in Carcinoembryonic Antigen (CEA)	Cycle 1-9 Day 1, and end of treatment/ safety follow-up (30 days after the last dose). Each cycle was 21 days	CEA was the tumour biomarker used to test cancer. Disease progression is indicated by CEA tumor marker elevation.

Countries

Canada, United States

Participant flow

Pre-assignment details

This study was planned to have two parts. Part 1 was dose escalation and confirmation, and Part 2 was a cohort expansion. The cohort expansion phase (Part 2) was not initiated due to Sponsor's business decision.

Participants by arm

Arm	Count
Arm A: MK-8353 50 mg + Pembrolizumab Participants received MK-8353 50 mg orally (PO) two times each day (BID) on Days 1 through 21 of each 21-day cycle PLUS pembrolizumab (pembro) 200 mg intravenously (IV) on Day 1 of each 21-day cycle for up to 35 cycles.	14
Arm A: MK-8353 100 mg + Pembrolizumab Participants received MK-8353 100 mg orally (PO) two times each day (BID) on Days 1 through 21 of each 21-day cycle PLUS pembrolizumab (pembro) 200 mg intravenously (IV) on Day 1 of each 21-day cycle for up to 35 cycles.	1
Arm A: MK-8353 50 + 100 mg + Pembrolizumab Participants received MK-8353 50 mg plus 100 mg orally (PO) two times each day (BID) on Days 1 through 21 of each 21-day cycle PLUS pembrolizumab (pembro) 200 mg intravenously (IV) on Day 1 of each 21-day cycle for up to 35 cycles.	3
Arm A: MK-8353 350 mg + Pembrolizumab Participants received MK-8353 350 mg orally (PO) two times each day (BID) on Days 1 through 21 of each 21-day cycle PLUS pembrolizumab (pembro) 200 mg intravenously (IV) on Day 1 of each 21-day cycle for up to 35 cycles.	4
Arm B: MK-8353 50 mg + Pembrolizumab Participants received MK-8353 PO 50 mg once each day (QD) on Days 1 through 21 of each 21-day cycle PLUS pembrolizumab 200 mg IV on Day 1 of each 21-day cycle for up to 35 cycles.	4
Arm B: MK-8353 100 mg + Pembrolizumab Participants received MK-8353 PO 100 mg once each day (QD) on Days 1 through 21 of each 21-day cycle PLUS pembrolizumab 200 mg IV on Day 1 of each 21-day cycle for up to 35 cycles.	3
Arm B: MK-8353 150 mg + Pembrolizumab Participants received MK-8353 PO 150 mg once each day (QD) on Days 1 through 21 of each 21-day cycle PLUS pembrolizumab 200 mg IV on Day 1 of each 21-day cycle for up to 35 cycles.	4
Arm B: MK-8353 200 mg + Pembrolizumab Participants received MK-8353 PO 200 mg once each day (QD) on Days 1 through 21 of each 21-day cycle PLUS pembrolizumab 200 mg IV on Day 1 of each 21-day cycle for up to 35 cycles.	7
Arm B: MK-8353 300 mg + Pembrolizumab Participants received MK-8353 PO 300 mg once each day (QD) on Days 1 through 21 of each 21-day cycle PLUS pembrolizumab 200 mg IV on Day 1 of each 21-day cycle for up to 35 cycles.	10
Arm B: MK-8353 400 mg + Pembrolizumab Participants received MK-8353 PO 400 mg once each day (QD) on Days 1 through 21 of each 21-day cycle PLUS pembrolizumab 200 mg IV on Day 1 of each 21-day cycle for up to 35 cycles.	14
Arm B: MK-8353 600 mg + Pembrolizumab Participants received MK-8353 PO 600 mg once each day (QD) on Days 1 through 21 of each 21-day cycle PLUS pembrolizumab 200 mg IV on Day 1 of each 21-day cycle for up to 35 cycles.	8
Arm C: MK-8353 100 mg + Pembrolizumab Participants received MK-8353 100 mg PO QD on Days 1 to 7, Days 15 to 21 and Days 29 to 35 PLUS pembrolizumab 200 mg IV on Day 1 and Day 22 of each 42-day period (based on 2 cycles of 21 days) for up to 35 cycles.	3
Arm C: MK-8353 150 mg + Pembrolizumab Participants received MK-8353 150 mg PO QD on Days 1 to 7, Days 15 to 21 and Days 29 to 35 PLUS pembrolizumab 200 mg IV on Day 1 and Day 22 of each 42-day period (based on 2 cycles of 21 days) for up to 35 cycles.	14
Arm C: MK-8353 200 mg + Pembrolizumab Participants received MK-8353 200 mg PO QD on Days 1 to 7, Days 15 to 21 and Days 29 to 35 PLUS pembrolizumab 200 mg IV on Day 1 and Day 22 of each 42-day period (based on 2 cycles of 21 days) for up to 35 cycles.	11
Arm C: MK-8353 300 mg + Pembrolizumab Participants received MK-8353 300 mg PO QD on Days 1 to 7, Days 15 to 21 and Days 29 to 35 PLUS pembrolizumab 200 mg IV on Day 1 and Day 22 of each 42-day period (based on 2 cycles of 21 days) for up to 35 cycles.	11
Total	111

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG003	FG004	FG005	FG006	FG007	FG008	FG009	FG010	FG011	FG012	FG013	FG014
Overall Study	Death	11	1	3	3	2	2	3	4	8	11	3	2	11	10	9
Overall Study	Lost to Follow-up	0	0	0	0	1	0	0	1	0	0	0	0	0	0	1
Overall Study	Physician Decision	0	0	0	0	0	0	0	1	0	0	1	0	0	0	0
Overall Study	Screen Failure	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Overall Study	Sponsor Decision	0	0	0	1	0	0	1	1	1	2	2	0	1	0	1
Overall Study	Withdrawal by Subject	3	0	0	0	1	1	0	0	1	1	2	1	1	1	0

Baseline characteristics

Characteristic	Total	Arm C: MK-8353 300 mg + Pembrolizumab	Arm C: MK-8353 200 mg + Pembrolizumab	Arm C: MK-8353 150 mg + Pembrolizumab	Arm C: MK-8353 100 mg + Pembrolizumab	Arm B: MK-8353 600 mg + Pembrolizumab	Arm B: MK-8353 400 mg + Pembrolizumab	Arm B: MK-8353 300 mg + Pembrolizumab	Arm B: MK-8353 200 mg + Pembrolizumab	Arm B: MK-8353 150 mg + Pembrolizumab	Arm B: MK-8353 100 mg + Pembrolizumab	Arm B: MK-8353 50 mg + Pembrolizumab	Arm A: MK-8353 350 mg + Pembrolizumab	Arm A: MK-8353 50 + 100 mg + Pembrolizumab	Arm A: MK-8353 100 mg + Pembrolizumab	Arm A: MK-8353 50 mg + Pembrolizumab
Age, Continuous	58.3 Years STANDARD_DEVIATION 10.4	57.6 Years STANDARD_DEVIATION 12.8	64.1 Years STANDARD_DEVIATION 8.2	53.0 Years STANDARD_DEVIATION 8.9	58.0 Years STANDARD_DEVIATION 19.3	62.1 Years STANDARD_DEVIATION 11.6	59.5 Years STANDARD_DEVIATION 8.1	61.1 Years STANDARD_DEVIATION 10.3	63.1 Years STANDARD_DEVIATION 8.5	57.5 Years STANDARD_DEVIATION 6.2	60.0 Years STANDARD_DEVIATION 14.5	57.5 Years STANDARD_DEVIATION 11.1	46.0 Years STANDARD_DEVIATION 8.7	59.7 Years STANDARD_DEVIATION 13	51.0 Years	54.8 Years STANDARD_DEVIATION 10.1
Eastern Cooperative Oncology Group (ECOG) Performance Status ECOG = 0	41 Participants	6 Participants	3 Participants	6 Participants	2 Participants	1 Participants	7 Participants	2 Participants	4 Participants	0 Participants	1 Participants	2 Participants	2 Participants	0 Participants	0 Participants	5 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status ECOG = 1	69 Participants	5 Participants	8 Participants	7 Participants	1 Participants	7 Participants	7 Participants	8 Participants	3 Participants	4 Participants	2 Participants	2 Participants	2 Participants	3 Participants	1 Participants	9 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status Missing	1 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	94 Participants	9 Participants	11 Participants	12 Participants	3 Participants	8 Participants	12 Participants	8 Participants	4 Participants	2 Participants	3 Participants	3 Participants	4 Participants	2 Participants	1 Participants	12 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	17 Participants	2 Participants	0 Participants	2 Participants	0 Participants	0 Participants	2 Participants	2 Participants	3 Participants	2 Participants	0 Participants	1 Participants	0 Participants	1 Participants	0 Participants	2 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	9 Participants	2 Participants	3 Participants	1 Participants	0 Participants	1 Participants	0 Participants	1 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Black or African American	3 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	1 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	4 Participants	2 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) White	95 Participants	7 Participants	8 Participants	12 Participants	3 Participants	6 Participants	13 Participants	9 Participants	5 Participants	3 Participants	3 Participants	4 Participants	4 Participants	3 Participants	1 Participants	14 Participants
Sex: Female, Male Female	49 Participants	7 Participants	2 Participants	8 Participants	3 Participants	5 Participants	5 Participants	2 Participants	4 Participants	2 Participants	0 Participants	2 Participants	1 Participants	2 Participants	1 Participants	5 Participants
Sex: Female, Male Male	62 Participants	4 Participants	9 Participants	6 Participants	0 Participants	3 Participants	9 Participants	8 Participants	3 Participants	2 Participants	3 Participants	2 Participants	3 Participants	1 Participants	0 Participants	9 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk	EG004 affected / at risk	EG005 affected / at risk	EG006 affected / at risk	EG007 affected / at risk	EG008 affected / at risk	EG009 affected / at risk	EG010 affected / at risk	EG011 affected / at risk	EG012 affected / at risk	EG013 affected / at risk	EG014 affected / at risk
deaths Total, all-cause mortality	13 / 14	1 / 1	3 / 3	3 / 4	3 / 4	2 / 3	3 / 4	4 / 7	8 / 10	11 / 14	5 / 8	3 / 3	11 / 14	10 / 11	9 / 11
other Total, other adverse events	14 / 14	1 / 1	3 / 3	4 / 4	4 / 4	3 / 3	4 / 4	7 / 7	10 / 10	14 / 14	8 / 8	3 / 3	13 / 13	11 / 11	10 / 11
serious Total, serious adverse events	6 / 14	1 / 1	0 / 3	3 / 4	1 / 4	1 / 3	2 / 4	1 / 7	3 / 10	3 / 14	5 / 8	1 / 3	5 / 13	4 / 11	4 / 11

Outcome results

Primary

Number of Participants Who Discontinued Study Drug Due to an Adverse Event (AE)

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 who discontinued treatment due to an AE was assessed.

Time frame: Up to 24 months

Population: The analysis population consisted of all participants who received at least 1 dose of study treatment.

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Arm A: MK-8353 50 mg + Pembrolizumab	Number of Participants Who Discontinued Study Drug Due to an Adverse Event (AE)	1 Participants
Arm A: MK-8353 100 mg + Pembrolizumab	Number of Participants Who Discontinued Study Drug Due to an Adverse Event (AE)	1 Participants
Arm A: MK-8353 50 + 100 mg + Pembrolizumab	Number of Participants Who Discontinued Study Drug Due to an Adverse Event (AE)	0 Participants
Arm A: MK-8353 350 mg + Pembrolizumab	Number of Participants Who Discontinued Study Drug Due to an Adverse Event (AE)	2 Participants
Arm B: MK-8353 50 mg + Pembrolizumab	Number of Participants Who Discontinued Study Drug Due to an Adverse Event (AE)	0 Participants
Arm B: MK-8353 100 mg + Pembrolizumab	Number of Participants Who Discontinued Study Drug Due to an Adverse Event (AE)	0 Participants
Arm B: MK-8353 150 mg + Pembrolizumab	Number of Participants Who Discontinued Study Drug Due to an Adverse Event (AE)	0 Participants
Arm B: MK-8353 200 mg + Pembrolizumab	Number of Participants Who Discontinued Study Drug Due to an Adverse Event (AE)	1 Participants
Arm B: MK-8353 300 mg + Pembrolizumab	Number of Participants Who Discontinued Study Drug Due to an Adverse Event (AE)	2 Participants
Arm B: MK-8353 400 mg + Pembrolizumab	Number of Participants Who Discontinued Study Drug Due to an Adverse Event (AE)	4 Participants
Arm B: MK-8353 600 mg + Pembrolizumab	Number of Participants Who Discontinued Study Drug Due to an Adverse Event (AE)	2 Participants
Arm C: MK-8353 100 mg + Pembrolizumab	Number of Participants Who Discontinued Study Drug Due to an Adverse Event (AE)	0 Participants
Arm C: MK-8353 150 mg + Pembrolizumab	Number of Participants Who Discontinued Study Drug Due to an Adverse Event (AE)	3 Participants
Arm C: MK-8353 200 mg + Pembrolizumab	Number of Participants Who Discontinued Study Drug Due to an Adverse Event (AE)	2 Participants
Arm C: MK-8353 300 mg + Pembrolizumab	Number of Participants Who Discontinued Study Drug Due to an Adverse Event (AE)	0 Participants

Primary

Number of Participants Who Experienced an Adverse Event (AE)

Number of participants who experienced an AE was defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study therapy and irrespective of causality to study treatment

Time frame: Up to 27 months

Population: The analysis population consisted of all participants who received at least 1 dose of study treatment.

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Arm A: MK-8353 50 mg + Pembrolizumab	Number of Participants Who Experienced an Adverse Event (AE)	14 Participants
Arm A: MK-8353 100 mg + Pembrolizumab	Number of Participants Who Experienced an Adverse Event (AE)	1 Participants
Arm A: MK-8353 50 + 100 mg + Pembrolizumab	Number of Participants Who Experienced an Adverse Event (AE)	3 Participants
Arm A: MK-8353 350 mg + Pembrolizumab	Number of Participants Who Experienced an Adverse Event (AE)	4 Participants
Arm B: MK-8353 50 mg + Pembrolizumab	Number of Participants Who Experienced an Adverse Event (AE)	4 Participants
Arm B: MK-8353 100 mg + Pembrolizumab	Number of Participants Who Experienced an Adverse Event (AE)	3 Participants
Arm B: MK-8353 150 mg + Pembrolizumab	Number of Participants Who Experienced an Adverse Event (AE)	4 Participants
Arm B: MK-8353 200 mg + Pembrolizumab	Number of Participants Who Experienced an Adverse Event (AE)	7 Participants
Arm B: MK-8353 300 mg + Pembrolizumab	Number of Participants Who Experienced an Adverse Event (AE)	10 Participants
Arm B: MK-8353 400 mg + Pembrolizumab	Number of Participants Who Experienced an Adverse Event (AE)	14 Participants
Arm B: MK-8353 600 mg + Pembrolizumab	Number of Participants Who Experienced an Adverse Event (AE)	8 Participants
Arm C: MK-8353 100 mg + Pembrolizumab	Number of Participants Who Experienced an Adverse Event (AE)	3 Participants
Arm C: MK-8353 150 mg + Pembrolizumab	Number of Participants Who Experienced an Adverse Event (AE)	13 Participants
Arm C: MK-8353 200 mg + Pembrolizumab	Number of Participants Who Experienced an Adverse Event (AE)	11 Participants
Arm C: MK-8353 300 mg + Pembrolizumab	Number of Participants Who Experienced an Adverse Event (AE)	11 Participants

Primary

Number of Participants Who Experienced Dose-Limiting Toxicity (DLT)

DLT was defined as a treatment-related adverse event (AE) including the following: Grade (Gr) 4 nonhematologic toxicity (not laboratory), Gr 4 hematologic toxicity lasting ≥7 days, except thrombocytopenia or Gr 4 thrombocytopenia of any duration or Gr 3 thrombocytopenia associated with clinically significant bleeding, Gr 3 non-hematological AE with the exception of fatigue lasting \>3 days despite optimal supportive care, any Gr 3 or Gr 4 nonhematologic laboratory value if medical intervention is required to treat the subject, or abnormality leads to hospitalization or abnormality persists for \>1 week, Gr 3 or Gr 4 febrile neutropenia, prolonged delay (\>2 weeks) in initiating Cycle 2 due to treatment-related toxicity, any treatment-related toxicity that causes the subject to discontinue treatment during Cycle 1, missing \>25% of MK-8353 doses as a result of drug-related AE(s) during the first cycle, Gr 5 toxicity.

Time frame: Cycle 1 (Arms A, B & C: Up to 21 days)

Population: The DLT evaluable population consisted of all participants who completed the first cycle of study treatment or who discontinued from the study due to a drug-related AE.

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Arm A: MK-8353 50 mg + Pembrolizumab	Number of Participants Who Experienced Dose-Limiting Toxicity (DLT)	0 Participants
Arm A: MK-8353 100 mg + Pembrolizumab	Number of Participants Who Experienced Dose-Limiting Toxicity (DLT)	1 Participants
Arm A: MK-8353 50 + 100 mg + Pembrolizumab	Number of Participants Who Experienced Dose-Limiting Toxicity (DLT)	2 Participants
Arm A: MK-8353 350 mg + Pembrolizumab	Number of Participants Who Experienced Dose-Limiting Toxicity (DLT)	3 Participants
Arm B: MK-8353 50 mg + Pembrolizumab	Number of Participants Who Experienced Dose-Limiting Toxicity (DLT)	0 Participants
Arm B: MK-8353 100 mg + Pembrolizumab	Number of Participants Who Experienced Dose-Limiting Toxicity (DLT)	0 Participants
Arm B: MK-8353 150 mg + Pembrolizumab	Number of Participants Who Experienced Dose-Limiting Toxicity (DLT)	0 Participants
Arm B: MK-8353 200 mg + Pembrolizumab	Number of Participants Who Experienced Dose-Limiting Toxicity (DLT)	1 Participants
Arm B: MK-8353 300 mg + Pembrolizumab	Number of Participants Who Experienced Dose-Limiting Toxicity (DLT)	0 Participants
Arm B: MK-8353 400 mg + Pembrolizumab	Number of Participants Who Experienced Dose-Limiting Toxicity (DLT)	4 Participants
Arm B: MK-8353 600 mg + Pembrolizumab	Number of Participants Who Experienced Dose-Limiting Toxicity (DLT)	3 Participants
Arm C: MK-8353 100 mg + Pembrolizumab	Number of Participants Who Experienced Dose-Limiting Toxicity (DLT)	0 Participants
Arm C: MK-8353 150 mg + Pembrolizumab	Number of Participants Who Experienced Dose-Limiting Toxicity (DLT)	2 Participants
Arm C: MK-8353 200 mg + Pembrolizumab	Number of Participants Who Experienced Dose-Limiting Toxicity (DLT)	1 Participants
Arm C: MK-8353 300 mg + Pembrolizumab	Number of Participants Who Experienced Dose-Limiting Toxicity (DLT)	2 Participants

Secondary

Objective Response Rate (ORR) Based on Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by the Investigator

ORR was defined as the percentage of the participants in the analysis population who have a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters). The ORR per RECIST 1.1 as assessed by Investigator was presented.

Time frame: Up to 24 months

Population: Analysis population consisted of all participants who had a baseline scan with measurable disease by investigator assessment and who were administered a dose of the study treatment.

Arm	Measure	Value (NUMBER)
Arm A: MK-8353 50 mg + Pembrolizumab	Objective Response Rate (ORR) Based on Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by the Investigator	0.0 Percentage of Participants
Arm A: MK-8353 100 mg + Pembrolizumab	Objective Response Rate (ORR) Based on Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by the Investigator	0.0 Percentage of Participants
Arm A: MK-8353 50 + 100 mg + Pembrolizumab	Objective Response Rate (ORR) Based on Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by the Investigator	0.0 Percentage of Participants
Arm A: MK-8353 350 mg + Pembrolizumab	Objective Response Rate (ORR) Based on Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by the Investigator	0.0 Percentage of Participants
Arm B: MK-8353 50 mg + Pembrolizumab	Objective Response Rate (ORR) Based on Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by the Investigator	0.0 Percentage of Participants
Arm B: MK-8353 100 mg + Pembrolizumab	Objective Response Rate (ORR) Based on Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by the Investigator	0.0 Percentage of Participants
Arm B: MK-8353 150 mg + Pembrolizumab	Objective Response Rate (ORR) Based on Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by the Investigator	0.0 Percentage of Participants
Arm B: MK-8353 200 mg + Pembrolizumab	Objective Response Rate (ORR) Based on Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by the Investigator	0.0 Percentage of Participants
Arm B: MK-8353 300 mg + Pembrolizumab	Objective Response Rate (ORR) Based on Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by the Investigator	20.0 Percentage of Participants
Arm B: MK-8353 400 mg + Pembrolizumab	Objective Response Rate (ORR) Based on Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by the Investigator	21.4 Percentage of Participants
Arm B: MK-8353 600 mg + Pembrolizumab	Objective Response Rate (ORR) Based on Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by the Investigator	25.0 Percentage of Participants
Arm C: MK-8353 100 mg + Pembrolizumab	Objective Response Rate (ORR) Based on Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by the Investigator	0.0 Percentage of Participants
Arm C: MK-8353 150 mg + Pembrolizumab	Objective Response Rate (ORR) Based on Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by the Investigator	7.7 Percentage of Participants
Arm C: MK-8353 200 mg + Pembrolizumab	Objective Response Rate (ORR) Based on Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by the Investigator	0.0 Percentage of Participants
Arm C: MK-8353 300 mg + Pembrolizumab	Objective Response Rate (ORR) Based on Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by the Investigator	0.0 Percentage of Participants

Secondary

Percent Change in Cancer Antigen 125 (CA-125)

CA-125 was the tumour biomarker used to test cancer. Disease progression is indicated by CA-125 tumor marker elevation.

Time frame: Cycle 1-8 Day 1, and end of treatment/ safety follow-up (30 days after the last dose). Each cycle was 21 days.

Population: Analysis population consisted of all participants who had a baseline scan with measurable disease by investigator assessment, CA-125 data available for each timepoint and who were administered a dose of the study treatment.

Arm	Measure	Group	Value (MEAN)
Arm A: MK-8353 50 mg + Pembrolizumab	Percent Change in Cancer Antigen 125 (CA-125)	End of treatment/ Safety Follow-up	118.18 Percent Change
Arm A: MK-8353 50 mg + Pembrolizumab	Percent Change in Cancer Antigen 125 (CA-125)	Day 1 Cycle 6	50.0 Percent Change
Arm A: MK-8353 50 mg + Pembrolizumab	Percent Change in Cancer Antigen 125 (CA-125)	Day 1 Cycle 3	42.69 Percent Change
Arm A: MK-8353 50 mg + Pembrolizumab	Percent Change in Cancer Antigen 125 (CA-125)	Day 1 Cycle 5	153.25 Percent Change
Arm A: MK-8353 50 mg + Pembrolizumab	Percent Change in Cancer Antigen 125 (CA-125)	Day 1 Cycle 4	103.10 Percent Change
Arm A: MK-8353 50 mg + Pembrolizumab	Percent Change in Cancer Antigen 125 (CA-125)	Day 1 Cycle 2	15.47 Percent Change
Arm A: MK-8353 50 mg + Pembrolizumab	Percent Change in Cancer Antigen 125 (CA-125)	Day 1 Cycle 8	3.3 Percent Change
Arm A: MK-8353 50 mg + Pembrolizumab	Percent Change in Cancer Antigen 125 (CA-125)	Day 1 Cycle 7	36.7 Percent Change
Arm A: MK-8353 50 + 100 mg + Pembrolizumab	Percent Change in Cancer Antigen 125 (CA-125)	End of treatment/ Safety Follow-up	101.7 Percent Change
Arm A: MK-8353 50 + 100 mg + Pembrolizumab	Percent Change in Cancer Antigen 125 (CA-125)	Day 1 Cycle 2	17.2 Percent Change
Arm A: MK-8353 50 + 100 mg + Pembrolizumab	Percent Change in Cancer Antigen 125 (CA-125)	Day 1 Cycle 3	33.0 Percent Change
Arm B: MK-8353 50 mg + Pembrolizumab	Percent Change in Cancer Antigen 125 (CA-125)	Day 1 Cycle 4	-13.3 Percent Change
Arm B: MK-8353 50 mg + Pembrolizumab	Percent Change in Cancer Antigen 125 (CA-125)	Day 1 Cycle 2	-13.3 Percent Change
Arm B: MK-8353 50 mg + Pembrolizumab	Percent Change in Cancer Antigen 125 (CA-125)	Day 1 Cycle 6	-6.7 Percent Change
Arm B: MK-8353 50 mg + Pembrolizumab	Percent Change in Cancer Antigen 125 (CA-125)	Day 1 Cycle 3	-13.3 Percent Change
Arm B: MK-8353 50 mg + Pembrolizumab	Percent Change in Cancer Antigen 125 (CA-125)	Day 1 Cycle 5	-13.3 Percent Change
Arm B: MK-8353 100 mg + Pembrolizumab	Percent Change in Cancer Antigen 125 (CA-125)	Day 1 Cycle 2	68.3 Percent Change
Arm B: MK-8353 100 mg + Pembrolizumab	Percent Change in Cancer Antigen 125 (CA-125)	End of treatment/ Safety Follow-up	329.3 Percent Change
Arm B: MK-8353 150 mg + Pembrolizumab	Percent Change in Cancer Antigen 125 (CA-125)	Day 1 Cycle 3	-31.21 Percent Change
Arm B: MK-8353 150 mg + Pembrolizumab	Percent Change in Cancer Antigen 125 (CA-125)	End of treatment/ Safety Follow-up	2.69 Percent Change
Arm B: MK-8353 150 mg + Pembrolizumab	Percent Change in Cancer Antigen 125 (CA-125)	Day 1 Cycle 5	-76.8 Percent Change
Arm B: MK-8353 150 mg + Pembrolizumab	Percent Change in Cancer Antigen 125 (CA-125)	Day 1 Cycle 4	-24.19 Percent Change
Arm B: MK-8353 150 mg + Pembrolizumab	Percent Change in Cancer Antigen 125 (CA-125)	Day 1 Cycle 6	-75.0 Percent Change
Arm B: MK-8353 150 mg + Pembrolizumab	Percent Change in Cancer Antigen 125 (CA-125)	Day 1 Cycle 2	83.75 Percent Change
Arm B: MK-8353 200 mg + Pembrolizumab	Percent Change in Cancer Antigen 125 (CA-125)	Day 1 Cycle 4	42.26 Percent Change
Arm B: MK-8353 200 mg + Pembrolizumab	Percent Change in Cancer Antigen 125 (CA-125)	Day 1 Cycle 2	39.85 Percent Change
Arm B: MK-8353 200 mg + Pembrolizumab	Percent Change in Cancer Antigen 125 (CA-125)	Day 1 Cycle 3	80.55 Percent Change
Arm B: MK-8353 200 mg + Pembrolizumab	Percent Change in Cancer Antigen 125 (CA-125)	Day 1 Cycle 5	22.2 Percent Change
Arm B: MK-8353 200 mg + Pembrolizumab	Percent Change in Cancer Antigen 125 (CA-125)	End of treatment/ Safety Follow-up	256.48 Percent Change
Arm B: MK-8353 300 mg + Pembrolizumab	Percent Change in Cancer Antigen 125 (CA-125)	End of treatment/ Safety Follow-up	38.6 Percent Change
Arm B: MK-8353 400 mg + Pembrolizumab	Percent Change in Cancer Antigen 125 (CA-125)	End of treatment/ Safety Follow-up	695.94 Percent Change
Arm B: MK-8353 600 mg + Pembrolizumab	Percent Change in Cancer Antigen 125 (CA-125)	Day 1 Cycle 5	-88.89 Percent Change
Arm B: MK-8353 600 mg + Pembrolizumab	Percent Change in Cancer Antigen 125 (CA-125)	Day 1 Cycle 8	-90.9 Percent Change
Arm B: MK-8353 600 mg + Pembrolizumab	Percent Change in Cancer Antigen 125 (CA-125)	Day 1 Cycle 2	11.00 Percent Change
Arm B: MK-8353 600 mg + Pembrolizumab	Percent Change in Cancer Antigen 125 (CA-125)	End of treatment/ Safety Follow-up	-30.24 Percent Change
Arm B: MK-8353 600 mg + Pembrolizumab	Percent Change in Cancer Antigen 125 (CA-125)	Day 1 Cycle 3	262.56 Percent Change
Arm B: MK-8353 600 mg + Pembrolizumab	Percent Change in Cancer Antigen 125 (CA-125)	Day 1 Cycle 6	-88.89 Percent Change
Arm B: MK-8353 600 mg + Pembrolizumab	Percent Change in Cancer Antigen 125 (CA-125)	Day 1 Cycle 7	-89.9 Percent Change
Arm C: MK-8353 100 mg + Pembrolizumab	Percent Change in Cancer Antigen 125 (CA-125)	Day 1 Cycle 3	300.3 Percent Change
Arm C: MK-8353 100 mg + Pembrolizumab	Percent Change in Cancer Antigen 125 (CA-125)	Day 1 Cycle 2	367.6 Percent Change
Arm C: MK-8353 100 mg + Pembrolizumab	Percent Change in Cancer Antigen 125 (CA-125)	Day 1 Cycle 4	359.1 Percent Change
Arm C: MK-8353 100 mg + Pembrolizumab	Percent Change in Cancer Antigen 125 (CA-125)	Day 1 Cycle 5	451.9 Percent Change
Arm C: MK-8353 150 mg + Pembrolizumab	Percent Change in Cancer Antigen 125 (CA-125)	Day 1 Cycle 3	-78.8 Percent Change
Arm C: MK-8353 150 mg + Pembrolizumab	Percent Change in Cancer Antigen 125 (CA-125)	Day 1 Cycle 4	-78.8 Percent Change
Arm C: MK-8353 150 mg + Pembrolizumab	Percent Change in Cancer Antigen 125 (CA-125)	Day 1 Cycle 5	-82.4 Percent Change
Arm C: MK-8353 150 mg + Pembrolizumab	Percent Change in Cancer Antigen 125 (CA-125)	Day 1 Cycle 2	-60.00 Percent Change
Arm C: MK-8353 150 mg + Pembrolizumab	Percent Change in Cancer Antigen 125 (CA-125)	Day 1 Cycle 6	-87.1 Percent Change
Arm C: MK-8353 150 mg + Pembrolizumab	Percent Change in Cancer Antigen 125 (CA-125)	Day 1 Cycle 7	-84.7 Percent Change
Arm C: MK-8353 300 mg + Pembrolizumab	Percent Change in Cancer Antigen 125 (CA-125)	End of treatment/ Safety Follow-up	87.88 Percent Change
Arm C: MK-8353 300 mg + Pembrolizumab	Percent Change in Cancer Antigen 125 (CA-125)	Day 1 Cycle 8	-16.7 Percent Change
Arm C: MK-8353 300 mg + Pembrolizumab	Percent Change in Cancer Antigen 125 (CA-125)	Day 1 Cycle 7	-16.7 Percent Change
Arm C: MK-8353 300 mg + Pembrolizumab	Percent Change in Cancer Antigen 125 (CA-125)	Day 1 Cycle 6	-25.0 Percent Change
Arm C: MK-8353 300 mg + Pembrolizumab	Percent Change in Cancer Antigen 125 (CA-125)	Day 1 Cycle 2	36.36 Percent Change
Arm C: MK-8353 300 mg + Pembrolizumab	Percent Change in Cancer Antigen 125 (CA-125)	Day 1 Cycle 4	-10.05 Percent Change
Arm C: MK-8353 300 mg + Pembrolizumab	Percent Change in Cancer Antigen 125 (CA-125)	Day 1 Cycle 3	-5.10 Percent Change

Secondary

Percent Change in Carbohydrate Antigen (CA19-9)

CA19-9 was the tumour biomarker used to test cancer. Disease progression is indicated by CA19-9 tumor marker elevation

Time frame: Cycle 1-7 Day 1, and end of treatment/ safety follow-up (30 days after the last dose). Each cycle was 21 days.

Population: Analysis population consisted of all participants who had a baseline scan with measurable disease by investigator assessment, CA19-9 data available for each timepoint and who were administered a dose of the study treatment.

Arm	Measure	Group	Value (MEAN)
Arm A: MK-8353 50 mg + Pembrolizumab	Percent Change in Carbohydrate Antigen (CA19-9)	Day 1 Cycle 6	16.7 Percent Change
Arm A: MK-8353 50 mg + Pembrolizumab	Percent Change in Carbohydrate Antigen (CA19-9)	Day 1 Cycle 5	113.10 Percent Change
Arm A: MK-8353 50 mg + Pembrolizumab	Percent Change in Carbohydrate Antigen (CA19-9)	Day 1 Cycle 2	36.10 Percent Change
Arm A: MK-8353 50 mg + Pembrolizumab	Percent Change in Carbohydrate Antigen (CA19-9)	Day 1 Cycle 3	44.52 Percent Change
Arm A: MK-8353 50 mg + Pembrolizumab	Percent Change in Carbohydrate Antigen (CA19-9)	Day 1 Cycle 4	40.48 Percent Change
Arm A: MK-8353 50 mg + Pembrolizumab	Percent Change in Carbohydrate Antigen (CA19-9)	End of treatment/ Safety Follow-up	89.29 Percent Change
Arm A: MK-8353 50 mg + Pembrolizumab	Percent Change in Carbohydrate Antigen (CA19-9)	Day 1 Cycle 7	33.33 Percent Change
Arm A: MK-8353 50 + 100 mg + Pembrolizumab	Percent Change in Carbohydrate Antigen (CA19-9)	Day 1 Cycle 3	-23.1 Percent Change
Arm A: MK-8353 50 + 100 mg + Pembrolizumab	Percent Change in Carbohydrate Antigen (CA19-9)	Day 1 Cycle 2	-2.06 Percent Change
Arm B: MK-8353 50 mg + Pembrolizumab	Percent Change in Carbohydrate Antigen (CA19-9)	Day 1 Cycle 2	12.2 Percent Change
Arm B: MK-8353 50 mg + Pembrolizumab	Percent Change in Carbohydrate Antigen (CA19-9)	Day 1 Cycle 4	168.9 Percent Change
Arm B: MK-8353 50 mg + Pembrolizumab	Percent Change in Carbohydrate Antigen (CA19-9)	Day 1 Cycle 5	168.9 Percent Change
Arm B: MK-8353 50 mg + Pembrolizumab	Percent Change in Carbohydrate Antigen (CA19-9)	Day 1 Cycle 6	202.7 Percent Change
Arm B: MK-8353 50 mg + Pembrolizumab	Percent Change in Carbohydrate Antigen (CA19-9)	Day 1 Cycle 3	71.6 Percent Change
Arm B: MK-8353 100 mg + Pembrolizumab	Percent Change in Carbohydrate Antigen (CA19-9)	Day 1 Cycle 2	51.34 Percent Change
Arm B: MK-8353 100 mg + Pembrolizumab	Percent Change in Carbohydrate Antigen (CA19-9)	Day 1 Cycle 5	81.3 Percent Change
Arm B: MK-8353 100 mg + Pembrolizumab	Percent Change in Carbohydrate Antigen (CA19-9)	Day 1 Cycle 4	199.1 Percent Change
Arm B: MK-8353 100 mg + Pembrolizumab	Percent Change in Carbohydrate Antigen (CA19-9)	End of treatment/ Safety Follow-up	-99.5 Percent Change
Arm B: MK-8353 100 mg + Pembrolizumab	Percent Change in Carbohydrate Antigen (CA19-9)	Day 1 Cycle 3	63.4 Percent Change
Arm B: MK-8353 150 mg + Pembrolizumab	Percent Change in Carbohydrate Antigen (CA19-9)	Day 1 Cycle 4	-73.9 Percent Change
Arm B: MK-8353 150 mg + Pembrolizumab	Percent Change in Carbohydrate Antigen (CA19-9)	Day 1 Cycle 2	-73.9 Percent Change
Arm B: MK-8353 150 mg + Pembrolizumab	Percent Change in Carbohydrate Antigen (CA19-9)	End of treatment/ Safety Follow-up	-71.7 Percent Change
Arm B: MK-8353 150 mg + Pembrolizumab	Percent Change in Carbohydrate Antigen (CA19-9)	Day 1 Cycle 6	-73.9 Percent Change
Arm B: MK-8353 150 mg + Pembrolizumab	Percent Change in Carbohydrate Antigen (CA19-9)	Day 1 Cycle 3	78.3 Percent Change
Arm B: MK-8353 150 mg + Pembrolizumab	Percent Change in Carbohydrate Antigen (CA19-9)	Day 1 Cycle 5	-78.3 Percent Change
Arm B: MK-8353 200 mg + Pembrolizumab	Percent Change in Carbohydrate Antigen (CA19-9)	Day 1 Cycle 4	43.06 Percent Change
Arm B: MK-8353 200 mg + Pembrolizumab	Percent Change in Carbohydrate Antigen (CA19-9)	Day 1 Cycle 2	19.93 Percent Change
Arm B: MK-8353 200 mg + Pembrolizumab	Percent Change in Carbohydrate Antigen (CA19-9)	Day 1 Cycle 3	1.39 Percent Change
Arm B: MK-8353 200 mg + Pembrolizumab	Percent Change in Carbohydrate Antigen (CA19-9)	Day 1 Cycle 5	206.3 Percent Change
Arm B: MK-8353 300 mg + Pembrolizumab	Percent Change in Carbohydrate Antigen (CA19-9)	Day 1 Cycle 4	-91.1 Percent Change
Arm B: MK-8353 300 mg + Pembrolizumab	Percent Change in Carbohydrate Antigen (CA19-9)	Day 1 Cycle 2	64.28 Percent Change
Arm B: MK-8353 300 mg + Pembrolizumab	Percent Change in Carbohydrate Antigen (CA19-9)	End of treatment/ Safety Follow-up	1078.56 Percent Change
Arm B: MK-8353 300 mg + Pembrolizumab	Percent Change in Carbohydrate Antigen (CA19-9)	Day 1 Cycle 5	1346.4 Percent Change
Arm B: MK-8353 300 mg + Pembrolizumab	Percent Change in Carbohydrate Antigen (CA19-9)	Day 1 Cycle 3	189.69 Percent Change
Arm B: MK-8353 400 mg + Pembrolizumab	Percent Change in Carbohydrate Antigen (CA19-9)	End of treatment/ Safety Follow-up	-4.70 Percent Change
Arm B: MK-8353 400 mg + Pembrolizumab	Percent Change in Carbohydrate Antigen (CA19-9)	Day 1 Cycle 2	0.9 Percent Change
Arm B: MK-8353 600 mg + Pembrolizumab	Percent Change in Carbohydrate Antigen (CA19-9)	Day 1 Cycle 7	-99.1 Percent Change
Arm B: MK-8353 600 mg + Pembrolizumab	Percent Change in Carbohydrate Antigen (CA19-9)	Day 1 Cycle 2	-8.23 Percent Change
Arm B: MK-8353 600 mg + Pembrolizumab	Percent Change in Carbohydrate Antigen (CA19-9)	End of treatment/ Safety Follow-up	850.28 Percent Change
Arm B: MK-8353 600 mg + Pembrolizumab	Percent Change in Carbohydrate Antigen (CA19-9)	Day 1 Cycle 4	-98.8 Percent Change
Arm B: MK-8353 600 mg + Pembrolizumab	Percent Change in Carbohydrate Antigen (CA19-9)	Day 1 Cycle 3	514.26 Percent Change
Arm B: MK-8353 600 mg + Pembrolizumab	Percent Change in Carbohydrate Antigen (CA19-9)	Day 1 Cycle 5	-99.0 Percent Change
Arm C: MK-8353 100 mg + Pembrolizumab	Percent Change in Carbohydrate Antigen (CA19-9)	Day 1 Cycle 3	25.0 Percent Change
Arm C: MK-8353 100 mg + Pembrolizumab	Percent Change in Carbohydrate Antigen (CA19-9)	Day 1 Cycle 5	150.0 Percent Change
Arm C: MK-8353 100 mg + Pembrolizumab	Percent Change in Carbohydrate Antigen (CA19-9)	Day 1 Cycle 4	75.0 Percent Change
Arm C: MK-8353 100 mg + Pembrolizumab	Percent Change in Carbohydrate Antigen (CA19-9)	Day 1 Cycle 6	25.00 Percent Change
Arm C: MK-8353 100 mg + Pembrolizumab	Percent Change in Carbohydrate Antigen (CA19-9)	Day 1 Cycle 2	12.5 Percent Change
Arm C: MK-8353 150 mg + Pembrolizumab	Percent Change in Carbohydrate Antigen (CA19-9)	Day 1 Cycle 4	29.24 Percent Change
Arm C: MK-8353 150 mg + Pembrolizumab	Percent Change in Carbohydrate Antigen (CA19-9)	Day 1 Cycle 6	-10.5 Percent Change
Arm C: MK-8353 150 mg + Pembrolizumab	Percent Change in Carbohydrate Antigen (CA19-9)	Day 1 Cycle 2	100.88 Percent Change
Arm C: MK-8353 150 mg + Pembrolizumab	Percent Change in Carbohydrate Antigen (CA19-9)	Day 1 Cycle 7	50.0 Percent Change
Arm C: MK-8353 150 mg + Pembrolizumab	Percent Change in Carbohydrate Antigen (CA19-9)	Day 1 Cycle 3	119.07 Percent Change
Arm C: MK-8353 150 mg + Pembrolizumab	Percent Change in Carbohydrate Antigen (CA19-9)	Day 1 Cycle 5	50.0 Percent Change
Arm C: MK-8353 150 mg + Pembrolizumab	Percent Change in Carbohydrate Antigen (CA19-9)	End of treatment/ Safety Follow-up	538.54 Percent Change
Arm C: MK-8353 200 mg + Pembrolizumab	Percent Change in Carbohydrate Antigen (CA19-9)	Day 1 Cycle 3	-15.8 Percent Change
Arm C: MK-8353 200 mg + Pembrolizumab	Percent Change in Carbohydrate Antigen (CA19-9)	Day 1 Cycle 4	10.5 Percent Change
Arm C: MK-8353 200 mg + Pembrolizumab	Percent Change in Carbohydrate Antigen (CA19-9)	Day 1 Cycle 5	-5.3 Percent Change
Arm C: MK-8353 200 mg + Pembrolizumab	Percent Change in Carbohydrate Antigen (CA19-9)	Day 1 Cycle 2	-5.3 Percent Change
Arm C: MK-8353 200 mg + Pembrolizumab	Percent Change in Carbohydrate Antigen (CA19-9)	End of treatment/ Safety Follow-up	54.42 Percent Change
Arm C: MK-8353 300 mg + Pembrolizumab	Percent Change in Carbohydrate Antigen (CA19-9)	End of treatment/ Safety Follow-up	11152.37 Percent Change
Arm C: MK-8353 300 mg + Pembrolizumab	Percent Change in Carbohydrate Antigen (CA19-9)	Day 1 Cycle 4	450.7 Percent Change
Arm C: MK-8353 300 mg + Pembrolizumab	Percent Change in Carbohydrate Antigen (CA19-9)	Day 1 Cycle 3	799.42 Percent Change
Arm C: MK-8353 300 mg + Pembrolizumab	Percent Change in Carbohydrate Antigen (CA19-9)	Day 1 Cycle 2	240.00 Percent Change

Secondary

Percent Change in Carcinoembryonic Antigen (CEA)

CEA was the tumour biomarker used to test cancer. Disease progression is indicated by CEA tumor marker elevation.

Time frame: Cycle 1-9 Day 1, and end of treatment/ safety follow-up (30 days after the last dose). Each cycle was 21 days

Population: Analysis population consisted of all participants who had a baseline scan with measurable disease by investigator assessment, CEA data available for each timepoint and who were administered a dose of the study treatment.

Arm	Measure	Group	Value (MEAN)
Arm A: MK-8353 50 mg + Pembrolizumab	Percent Change in Carcinoembryonic Antigen (CEA)	Day 1 Cycle 2	2.08 Percent Change
Arm A: MK-8353 50 mg + Pembrolizumab	Percent Change in Carcinoembryonic Antigen (CEA)	Day 1 Cycle 4	-1.84 Percent Change
Arm A: MK-8353 50 mg + Pembrolizumab	Percent Change in Carcinoembryonic Antigen (CEA)	Day 1 Cycle 6	2.88 Percent Change
Arm A: MK-8353 50 mg + Pembrolizumab	Percent Change in Carcinoembryonic Antigen (CEA)	End of treatment/ Safety Follow-up	46.99 Percent Change
Arm A: MK-8353 50 mg + Pembrolizumab	Percent Change in Carcinoembryonic Antigen (CEA)	Day 1 Cycle 9	28.6 Percent Change
Arm A: MK-8353 50 mg + Pembrolizumab	Percent Change in Carcinoembryonic Antigen (CEA)	Day 1 Cycle 8	27.01 Percent Change
Arm A: MK-8353 50 mg + Pembrolizumab	Percent Change in Carcinoembryonic Antigen (CEA)	Day 1 Cycle 7	29.64 Percent Change
Arm A: MK-8353 50 mg + Pembrolizumab	Percent Change in Carcinoembryonic Antigen (CEA)	Day 1 Cycle 5	-8.08 Percent Change
Arm A: MK-8353 50 mg + Pembrolizumab	Percent Change in Carcinoembryonic Antigen (CEA)	Day 1 Cycle 3	45.35 Percent Change
Arm A: MK-8353 100 mg + Pembrolizumab	Percent Change in Carcinoembryonic Antigen (CEA)	End of treatment/ Safety Follow-up	200.00 Percent Change
Arm A: MK-8353 50 + 100 mg + Pembrolizumab	Percent Change in Carcinoembryonic Antigen (CEA)	Day 1 Cycle 3	5.6 Percent Change
Arm A: MK-8353 50 + 100 mg + Pembrolizumab	Percent Change in Carcinoembryonic Antigen (CEA)	Day 1 Cycle 2	8.3 Percent Change
Arm A: MK-8353 50 + 100 mg + Pembrolizumab	Percent Change in Carcinoembryonic Antigen (CEA)	End of treatment/ Safety Follow-up	-2.8 Percent Change
Arm A: MK-8353 350 mg + Pembrolizumab	Percent Change in Carcinoembryonic Antigen (CEA)	Day 1 Cycle 2	-0.27 Percent Change
Arm A: MK-8353 350 mg + Pembrolizumab	Percent Change in Carcinoembryonic Antigen (CEA)	Day 1 Cycle 5	66.67 Percent Change
Arm A: MK-8353 350 mg + Pembrolizumab	Percent Change in Carcinoembryonic Antigen (CEA)	End of treatment/ Safety Follow-up	-79.1 Percent Change
Arm A: MK-8353 350 mg + Pembrolizumab	Percent Change in Carcinoembryonic Antigen (CEA)	Day 1 Cycle 6	61.1 Percent Change
Arm A: MK-8353 350 mg + Pembrolizumab	Percent Change in Carcinoembryonic Antigen (CEA)	Day 1 Cycle 4	50.0 Percent Change
Arm B: MK-8353 50 mg + Pembrolizumab	Percent Change in Carcinoembryonic Antigen (CEA)	End of treatment/ Safety Follow-up	232.8 Percent Change
Arm B: MK-8353 50 mg + Pembrolizumab	Percent Change in Carcinoembryonic Antigen (CEA)	Day 1 Cycle 2	54.41 Percent Change
Arm B: MK-8353 50 mg + Pembrolizumab	Percent Change in Carcinoembryonic Antigen (CEA)	Day 1 Cycle 3	113.63 Percent Change
Arm B: MK-8353 50 mg + Pembrolizumab	Percent Change in Carcinoembryonic Antigen (CEA)	Day 1 Cycle 4	199.86 Percent Change
Arm B: MK-8353 50 mg + Pembrolizumab	Percent Change in Carcinoembryonic Antigen (CEA)	Day 1 Cycle 5	197.72 Percent Change
Arm B: MK-8353 50 mg + Pembrolizumab	Percent Change in Carcinoembryonic Antigen (CEA)	Day 1 Cycle 6	445.2 Percent Change
Arm B: MK-8353 100 mg + Pembrolizumab	Percent Change in Carcinoembryonic Antigen (CEA)	End of treatment/ Safety Follow-up	108.3 Percent Change
Arm B: MK-8353 100 mg + Pembrolizumab	Percent Change in Carcinoembryonic Antigen (CEA)	Day 1 Cycle 2	-6.72 Percent Change
Arm B: MK-8353 150 mg + Pembrolizumab	Percent Change in Carcinoembryonic Antigen (CEA)	Day 1 Cycle 5	-96.5 Percent Change
Arm B: MK-8353 150 mg + Pembrolizumab	Percent Change in Carcinoembryonic Antigen (CEA)	Day 1 Cycle 2	-80.1 Percent Change
Arm B: MK-8353 150 mg + Pembrolizumab	Percent Change in Carcinoembryonic Antigen (CEA)	Day 1 Cycle 4	-95.1 Percent Change
Arm B: MK-8353 150 mg + Pembrolizumab	Percent Change in Carcinoembryonic Antigen (CEA)	Day 1 Cycle 6	-96.6 Percent Change
Arm B: MK-8353 150 mg + Pembrolizumab	Percent Change in Carcinoembryonic Antigen (CEA)	Day 1 Cycle 3	-93.9 Percent Change
Arm B: MK-8353 150 mg + Pembrolizumab	Percent Change in Carcinoembryonic Antigen (CEA)	End of treatment/ Safety Follow-up	-93.7 Percent Change
Arm B: MK-8353 200 mg + Pembrolizumab	Percent Change in Carcinoembryonic Antigen (CEA)	Day 1 Cycle 2	-13.8 Percent Change
Arm B: MK-8353 200 mg + Pembrolizumab	Percent Change in Carcinoembryonic Antigen (CEA)	Day 1 Cycle 5	106.6 Percent Change
Arm B: MK-8353 200 mg + Pembrolizumab	Percent Change in Carcinoembryonic Antigen (CEA)	Day 1 Cycle 4	19.07 Percent Change
Arm B: MK-8353 200 mg + Pembrolizumab	Percent Change in Carcinoembryonic Antigen (CEA)	Day 1 Cycle 3	4.86 Percent Change
Arm B: MK-8353 300 mg + Pembrolizumab	Percent Change in Carcinoembryonic Antigen (CEA)	Day 1 Cycle 3	9.0 Percent Change
Arm B: MK-8353 300 mg + Pembrolizumab	Percent Change in Carcinoembryonic Antigen (CEA)	Day 1 Cycle 4	-38.1 Percent Change
Arm B: MK-8353 300 mg + Pembrolizumab	Percent Change in Carcinoembryonic Antigen (CEA)	Day 1 Cycle 2	21.6 Percent Change
Arm B: MK-8353 300 mg + Pembrolizumab	Percent Change in Carcinoembryonic Antigen (CEA)	Day 1 Cycle 5	-44.2 Percent Change
Arm B: MK-8353 300 mg + Pembrolizumab	Percent Change in Carcinoembryonic Antigen (CEA)	End of treatment/ Safety Follow-up	84.85 Percent Change
Arm B: MK-8353 400 mg + Pembrolizumab	Percent Change in Carcinoembryonic Antigen (CEA)	Day 1 Cycle 6	29.4 Percent Change
Arm B: MK-8353 400 mg + Pembrolizumab	Percent Change in Carcinoembryonic Antigen (CEA)	Day 1 Cycle 8	0.00 Percent Change
Arm B: MK-8353 400 mg + Pembrolizumab	Percent Change in Carcinoembryonic Antigen (CEA)	Day 1 Cycle 4	17.6 Percent Change
Arm B: MK-8353 400 mg + Pembrolizumab	Percent Change in Carcinoembryonic Antigen (CEA)	End of treatment/ Safety Follow-up	-7.67 Percent Change
Arm B: MK-8353 400 mg + Pembrolizumab	Percent Change in Carcinoembryonic Antigen (CEA)	Day 1 Cycle 9	23.5 Percent Change
Arm B: MK-8353 400 mg + Pembrolizumab	Percent Change in Carcinoembryonic Antigen (CEA)	Day 1 Cycle 2	46.01 Percent Change
Arm B: MK-8353 600 mg + Pembrolizumab	Percent Change in Carcinoembryonic Antigen (CEA)	Day 1 Cycle 2	18.68 Percent Change
Arm B: MK-8353 600 mg + Pembrolizumab	Percent Change in Carcinoembryonic Antigen (CEA)	End of treatment/ Safety Follow-up	56.51 Percent Change
Arm B: MK-8353 600 mg + Pembrolizumab	Percent Change in Carcinoembryonic Antigen (CEA)	Day 1 Cycle 3	66.7 Percent Change
Arm C: MK-8353 100 mg + Pembrolizumab	Percent Change in Carcinoembryonic Antigen (CEA)	Day 1 Cycle 2	7.75 Percent Change
Arm C: MK-8353 100 mg + Pembrolizumab	Percent Change in Carcinoembryonic Antigen (CEA)	Day 1 Cycle 4	178.49 Percent Change
Arm C: MK-8353 100 mg + Pembrolizumab	Percent Change in Carcinoembryonic Antigen (CEA)	Day 1 Cycle 5	50.00 Percent Change
Arm C: MK-8353 100 mg + Pembrolizumab	Percent Change in Carcinoembryonic Antigen (CEA)	Day 1 Cycle 3	35.17 Percent Change
Arm C: MK-8353 150 mg + Pembrolizumab	Percent Change in Carcinoembryonic Antigen (CEA)	Day 1 Cycle 7	70.0 Percent Change
Arm C: MK-8353 150 mg + Pembrolizumab	Percent Change in Carcinoembryonic Antigen (CEA)	Day 1 Cycle 6	24.7 Percent Change
Arm C: MK-8353 150 mg + Pembrolizumab	Percent Change in Carcinoembryonic Antigen (CEA)	Day 1 Cycle 2	47.43 Percent Change
Arm C: MK-8353 150 mg + Pembrolizumab	Percent Change in Carcinoembryonic Antigen (CEA)	Day 1 Cycle 5	42.31 Percent Change
Arm C: MK-8353 150 mg + Pembrolizumab	Percent Change in Carcinoembryonic Antigen (CEA)	Day 1 Cycle 3	129.52 Percent Change
Arm C: MK-8353 150 mg + Pembrolizumab	Percent Change in Carcinoembryonic Antigen (CEA)	Day 1 Cycle 4	36.58 Percent Change
Arm C: MK-8353 150 mg + Pembrolizumab	Percent Change in Carcinoembryonic Antigen (CEA)	End of treatment/ Safety Follow-up	58.14 Percent Change
Arm C: MK-8353 200 mg + Pembrolizumab	Percent Change in Carcinoembryonic Antigen (CEA)	Day 1 Cycle 3	23.8 Percent Change
Arm C: MK-8353 200 mg + Pembrolizumab	Percent Change in Carcinoembryonic Antigen (CEA)	Day 1 Cycle 4	-51.1 Percent Change
Arm C: MK-8353 200 mg + Pembrolizumab	Percent Change in Carcinoembryonic Antigen (CEA)	Day 1 Cycle 5	-67.8 Percent Change
Arm C: MK-8353 200 mg + Pembrolizumab	Percent Change in Carcinoembryonic Antigen (CEA)	End of treatment/ Safety Follow-up	42.64 Percent Change
Arm C: MK-8353 200 mg + Pembrolizumab	Percent Change in Carcinoembryonic Antigen (CEA)	Day 1 Cycle 6	-35.8 Percent Change
Arm C: MK-8353 200 mg + Pembrolizumab	Percent Change in Carcinoembryonic Antigen (CEA)	Day 1 Cycle 2	58.20 Percent Change
Arm C: MK-8353 300 mg + Pembrolizumab	Percent Change in Carcinoembryonic Antigen (CEA)	Day 1 Cycle 3	129.98 Percent Change
Arm C: MK-8353 300 mg + Pembrolizumab	Percent Change in Carcinoembryonic Antigen (CEA)	Day 1 Cycle 2	62.24 Percent Change
Arm C: MK-8353 300 mg + Pembrolizumab	Percent Change in Carcinoembryonic Antigen (CEA)	Day 1 Cycle 4	315.8 Percent Change
Arm C: MK-8353 300 mg + Pembrolizumab	Percent Change in Carcinoembryonic Antigen (CEA)	End of treatment/ Safety Follow-up	416.18 Percent Change

Source: ClinicalTrials.gov · Data processed: Feb 5, 2026

Study of MK-8353 in Combination With Pembrolizumab (MK-3475) in Participants With Advanced Malignancies (MK-8353-013)

Conditions

Brief summary

Related papers

Interventions

Sponsors

Study design

Eligibility

Inclusion criteria

Exclusion criteria

Design outcomes

Primary

Secondary

Countries

Participant flow

Pre-assignment details

Participants by arm

Withdrawals & dropouts

Baseline characteristics

Adverse events

Outcome results

Number of Participants Who Discontinued Study Drug Due to an Adverse Event (AE)

Number of Participants Who Experienced an Adverse Event (AE)

Number of Participants Who Experienced Dose-Limiting Toxicity (DLT)

Objective Response Rate (ORR) Based on Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by the Investigator

Percent Change in Cancer Antigen 125 (CA-125)

Percent Change in Carbohydrate Antigen (CA19-9)

Percent Change in Carcinoembryonic Antigen (CEA)