Study of MK-8353 in Combination With Pembrolizumab (MK-34... | NCT02972034

NCT02972034

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Derived Section

Miscellaneous Info Module

ID	Type	Description	Link
MK-8353-013	Other Identifier	Merck Protocol Number
2016-003478-42	EudraCT Number

Status Module

Sponsor/Collaborators Module

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
A: MK-8353 BID Continuous+Pembro	Experimental	Participants receive MK-8353 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.	Drug: MK-8353 Biological: Pembrolizumab
B: MK-8353 QD Continuous+Pembro	Experimental	Participants receive MK-8353 PO 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.	Drug: MK-8353 Biological: Pembrolizumab
C: MK-8353 QD 1 Week On/1 Week Off+Pembro	Experimental	Optional Arm: Participants receive MK-8353 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.	Drug: MK-8353 Biological: Pembrolizumab
D: MK-8353 QD Run-in→MK-8353 QD Continuous+Pembro	Experimental	Optional Arm: Participants undergo an MK-8353 PO QD run-in period from Day -14 to Day -1 prior to Cycle 1 during which they receive MK-8353 PO QD. After the run-in period, participants receive MK-8353 PO 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 36 cycles.	Drug: MK-8353

Interventions

Name	Type	Description	Arm Group Labels	Other Names
MK-8353	Drug	PO capsule	A: MK-8353 BID Continuous+Pembro B: MK-8353 QD Continuous+Pembro C: MK-8353 QD 1 Week On/1 Week Off+Pembro D: MK-8353 QD Run-in→MK-8353 QD Continuous+Pembro

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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	Up to 27 months
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.	Up to 24 months
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.	Cycle 1 (Arms A, B & C: Up to 21 days)

Secondary Outcomes

Measure	Description	Time Frame
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.

Eligibility Module

Eligibility Criteria

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.

Contacts/Locations Module

Name	Affiliation	Role
Medical Director	Merck Sharp & Dohme LLC	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Call for Information (Investigational Site 0002)		Grand Rapids	Michigan	49546	United States
Call for Information (Investigational Site 0001)

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
39276176	Result	Lakhani NJ, Burris H 3rd, Miller WH Jr, Huang M, Chen LC, Siu LL. A phase 1b study of the ERK inhibitor MK-8353 plus pembrolizumab in patients with advanced solid tumors. Invest New Drugs. 2024 Oct;42(5):581-589. doi: 10.1007/s10637-024-01461-z. Epub 2024 Sep 14.

Label	URL
Merck Oncology Clinical Trials Information	View source

IPD Sharing Statement Module

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.

Arm/Group Information

ID	Title	Description
FG000	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.
FG001	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.
FG002	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.
FG003	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.
FG004	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.
FG005	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.
FG006	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.
FG007	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.
FG008	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.
FG009	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.
FG010	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.
FG011	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.
FG012	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.
FG013	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.
FG014	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.

Periods

Title

Milestones

Reasons Not Completed

Overall Study

Type	Comment	Milestone Data
STARTED		FG00014 subjects FG0011 subjects FG0023 subjects FG0034 subjects FG0044 subjects FG0053 subjects FG0064 subjects FG0077 subjects FG00810 subjects FG00914 subjects FG0108 subjects FG0113 subjects FG01214 subjects FG01311 subjects FG01411 subjects
Treated		FG00014 subjects FG0011 subjects FG0023 subjects FG0034 subjects FG004
COMPLETED		FG0000 subjects FG0010 subjects FG0020 subjects FG0030 subjects FG004
NOT COMPLETED		FG00014 subjects FG0011 subjects FG0023 subjects FG0034 subjects FG004

Type	Comment	Reasons
Death		FG00011 subjects FG0011 subjects FG0023 subjects FG003

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	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.
BG001	Arm A: MK-8353 100 mg + Pembrolizumab

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Continuous			Mean

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

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

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

Posted

Count of Participants

Participants

Up to 27 months

ID	Title	Description
OG000	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.
OG001

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	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.

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 25.1	Systematic Assessment

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 25.1	Systematic Assessment

More Info Module

Certain Agreements

Title	Organization	Phone	Extension	Email
Senior Vice President, Global Clinical Development	Merck Sharp & Dohme LLC	1-800-672-6372		ClinicalTrialsDisclosure@merck.com

Uploaded Document Information

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_SAP	Yes	Yes	No	Study Protocol and Statistical Analysis Plan	Jun 28, 2021	Nov 22, 2023	Prot_SAP_000.pdf

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

ID	Term
D009369	Neoplasms
D015179	Colorectal Neoplasms

ID	Term
D007414	Intestinal Neoplasms
D005770	Gastrointestinal Neoplasms
D004067	Digestive System Neoplasms
D009371	Neoplasms by Site

Intervention Browse Module

ID	Term
C000632607	MK-8353
C582435	pembrolizumab

Masking Info

Biological: Pembrolizumab

EG0001 events1 affected14 at risk

EG0010 events0 affected1 at risk

EG0020 events0 affected3 at risk

EG0030 events0 affected4 at risk

EG0040 events0 affected4 at risk

EG0050 events0 affected3 at risk

EG0060 events0 affected4 at risk

EG0070 events0 affected7 at risk

EG0080 events0 affected10 at risk

EG0090 events0 affected14 at risk

EG0100 events0 affected8 at risk

EG0110 events0 affected3 at risk

EG0120 events0 affected13 at risk

EG0130 events0 affected11 at risk

EG0140 events0 affected11 at risk

EG0003 events2 affected14 at risk

EG0010 events0 affected1 at risk

EG0020 events0 affected3 at risk

EG0031 events1 affected4 at risk

EG0040 events0 affected4 at risk

EG0051 events1 affected3 at risk

EG0061 events1 affected4 at risk

EG0071 events1 affected7 at risk

EG0080 events0 affected10 at risk

EG0092 events2 affected14 at risk

EG0101 events1 affected8 at risk

EG0110 events0 affected3 at risk

EG0120 events0 affected13 at risk

EG0130 events0 affected11 at risk

EG0141 events1 affected11 at risk

OG0040.0(0.0 to 60.2)

OG0050.0(0.0 to 70.8)

OG0060.0(0.0 to 60.2)

OG0070.0(0.0 to 41.0)

OG00820.0(2.5 to 55.6)

OG00921.4(4.7 to 50.8)

OG01025.0(3.2 to 65.1)

OG0110.0(0.0 to 70.8)

OG0127.7(0.2 to 36.0)

OG0130.0(0.0 to 28.5)

OG0140.0(0.0 to 28.5)

OG00780.55(11.1 to 221.8)

OG010262.56(-87.9 to 613.0)

OG011300.3(300.3 to 300.3)

OG012-78.8(-78.8 to -78.8)

OG014-5.10(-23.5 to 13.3)

OG011359.1(359.1 to 359.1)

OG012-78.8(-78.8 to -78.8)

OG014-10.05(-11.8 to -8.3)

OG010-88.89(-88.89 to -88.89)

OG011451.9(451.9 to 451.9)

OG012-82.4(-82.4 to -82.4)

OG012-87.1(-87.1 to -87.1)

OG014-25.0(-25.0 to -25.0)

OG007256.48(157.1 to 355.8)

OG00838.6(38.6 to 38.6)

OG009695.94(164.3 to 1227.6)

OG010-30.24(-89.9 to 29.4)

OG01487.88(-11.8 to 376.9)

OG0074.86(-18.5 to 33.1)

OG0089.0(9.0 to 9.0)

OG01066.7(66.7 to 66.7)

OG01135.17(31.3 to 39.1)

OG012129.52(-10.5 to 525.0)

OG01323.8(23.8 to 23.8)

OG014129.98(-18.8 to 316.0)

OG00719.07(6.7 to 31.5)

OG008-38.1(-38.1 to -38.1)

OG00917.6(17.6 to 17.6)

OG011178.49(25.0 to 332.0)

OG01236.58(-10.5 to 91.7)

OG013-51.1(-51.1 to -51.1)

OG014315.8(315.8 to 315.8)

OG007106.6(106.6 to 106.6)

OG008-44.2(-44.2 to -44.2)

OG01150.00(50.00 to 50.00)

OG01242.31(-15.8 to 82.7)

OG013-67.8(-67.8 to -67.8)

OG00929.4(29.4 to 29.4)

OG01224.7(-21.1 to 70.0)

OG013-35.8(-35.8 to -35.8)

OG004232.8(232.8 to 232.8)

OG005108.3(108.3 to 108.3)

OG006-93.7(-93.7 to -93.7)

OG00884.85(52.7 to 117.0)

OG009-7.67(-17.6 to 9.1)

OG01056.51(-11.1 to 124.1)

OG01258.14(-7.3 to 141.7)

OG01342.64(-13.9 to 99.2)

OG014416.18(-6.3 to 1430.2)

OG00678.3(78.3 to 78.3)

OG0071.39(-22.2 to 25.0)

OG008189.69(-93.8 to 473.2)

OG010514.26(-98.0 to 1126.6)

OG01125.0(25.0 to 25.0)

OG012119.07(-30.6 to 362.8)

OG013-15.8(-15.8 to -15.8)

OG014799.42(-15.4 to 2153.9)

OG00743.06(11.1 to 75.0)

OG008-91.1(-91.1 to -91.1)

OG010-98.8(-98.8 to -98.8)

OG01175.0(75.0 to 75.0)

OG01229.24(25.0 to 33.5)

OG01310.5(10.5 to 10.5)

OG014450.7(450.7 to 450.7)

OG007206.3(206.3 to 206.3)

OG0081346.4(1346.4 to 1346.4)

OG010-99.0(-99.0 to -99.0)

OG011150.0(150.0 to 150.0)

OG01250.0(50.0 to 50.0)

OG013-5.3(-5.3 to -5.3)

OG012-10.5(-10.5 to -10.5)

OG009-4.70(-47.9 to 38.5)

OG010850.28(-99.5 to 3413.1)

OG012538.54(277.1 to 800.0)

OG01354.42(-2.5 to 139.5)

OG01411152.37(55.6 to 32853.8)