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NCT03745989

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

Completed Phase 1 Results posted Last updated 27 July 2023
What this trial tests

Phase 1 trial testing MK-8353 in Solid Tumors in 30 participants. Completed in 19 March 2021.

Timeline
22 February 2019
Primary endpoint
19 March 2021
19 March 2021

Quick facts

Lead sponsorMerck Sharp & Dohme LLC
PhasePhase 1
StatusCompleted
Study typeINTERVENTIONAL
Allocationna
Designsequential
Maskingnone
Primary purposetreatment
Enrollment30
Start date22 February 2019
Primary completion19 March 2021
Estimated completion19 March 2021
Sites5 locations across Switzerland, Canada, United States

Drugs / interventions tested

Conditions studied

Sponsor

Merck Sharp & Dohme LLC — full company profile →

Who can join

18 and older, any sex, with Solid Tumors. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants Experiencing Dose Limiting Toxicities Primary · Cycle 1 (3-week Cycle) (Up to 3 weeks)

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.

GroupValue95% CI
MK-8353 50 mg + Selumetinib 25 mg0
MK-8353 100 mg + Selumetinib 50 mg1
MK-8353 150 mg + Selumetinib 75 mg7
Number of Participants Experiencing Adverse Events Primary · ~90 days after last treatment dose (up to ~45 weeks)

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.

GroupValue95% CI
MK-8353 50 mg + Selumetinib 25 mg3
MK-8353 100 mg + Selumetinib 50 mg12
MK-8353 150 mg + Selumetinib 75 mg15
Number of Participants Discontinuing Study Treatment Due to AEs Primary · Up to ~33 weeks

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.

GroupValue95% CI
MK-8353 50 mg + Selumetinib 25 mg0
MK-8353 100 mg + Selumetinib 50 mg3
MK-8353 150 mg + Selumetinib 75 mg1
Area Under the Plasma Concentration-Time Curve for MK-8353 From Time 0 to 12 Hours Secondary · 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

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.

MK-8353, Cycle 1, Day 1
GroupValue95% CI
MK-8353 50 mg + Selumetinib 25 mg14.3± 62.7
MK-8353 100 mg + Selumetinib 50 mg9.66± 50.7
MK-8353 150 mg + Selumetinib 75 mg13.7± 32.8
MK-8353, Cycle 1, Day 4
GroupValue95% CI
MK-8353 50 mg + Selumetinib 25 mg16.7± 365.7
MK-8353 100 mg + Selumetinib 50 mg19.0± 36.9
MK-8353 150 mg + Selumetinib 75 mg20.9± 60.6
AUC0-12 for Selumetinib Secondary · 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

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

Selumetinib, Cycle 1, Day 1
GroupValue95% CI
MK-8353 50 mg + Selumetinib 25 mg2.99± 27.2
MK-8353 100 mg + Selumetinib 50 mg5.20± 63.2
MK-8353 150 mg + Selumetinib 75 mg10.9± 49.1
Selumetinib, Cycle 1, Day 4
GroupValue95% CI
MK-8353 50 mg + Selumetinib 25 mg3.80± 24.6
MK-8353 100 mg + Selumetinib 50 mg6.28± 75.3
MK-8353 150 mg + Selumetinib 75 mg12.7± 31.5
Minimum Observed Plasma Concentration for MK-8353 Secondary · 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

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."

MK-8353, Cycle 1, Day 1
GroupValue95% CI
MK-8353 50 mg + Selumetinib 25 mgNA± NA
MK-8353 100 mg + Selumetinib 50 mgNA± NA
MK-8353 150 mg + Selumetinib 75 mgNA± NA
MK-8353, Cycle 1 Day 4
GroupValue95% CI
MK-8353 50 mg + Selumetinib 25 mg0.695± 222.6
MK-8353 100 mg + Selumetinib 50 mg1.10± 50.6
MK-8353 150 mg + Selumetinib 75 mg1.47± 455.5
MK-8353, Cycle 2 Day 1
GroupValue95% CI
MK-8353 50 mg + Selumetinib 25 mg0.0361± 173.2
MK-8353 100 mg + Selumetinib 50 mg0.0313± 191.0
MK-8353 150 mg + Selumetinib 75 mg0.0166± 189.7
MK-8353, Cycle 2 Day 4
GroupValue95% CI
MK-8353 50 mg + Selumetinib 25 mg0.598± 172.6
MK-8353 100 mg + Selumetinib 50 mg0.995± 90.7
MK-8353 150 mg + Selumetinib 75 mg1.47± 84.8
Cmin for Selumetinib Secondary · 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

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."

Selumetinib, Cycle 1, Day 1
GroupValue95% CI
MK-8353 50 mg + Selumetinib 25 mgNA± NA
MK-8353 100 mg + Selumetinib 50 mgNA± NA
MK-8353 150 mg + Selumetinib 75 mgNA± NA
Selumetinib, Cycle 1, Day 4
GroupValue95% CI
MK-8353 50 mg + Selumetinib 25 mg0.101± 35.1
MK-8353 100 mg + Selumetinib 50 mg0.265± 38.9
MK-8353 150 mg + Selumetinib 75 mg0.456± 160.1
Selumetinib, Cycle 2, Day 1
GroupValue95% CI
MK-8353 50 mg + Selumetinib 25 mgNA± NA
MK-8353 100 mg + Selumetinib 50 mg0.00202± 232.9
MK-8353 150 mg + Selumetinib 75 mg0.00124± 215.7
Selumetinib, Cycle 2, Day 4
GroupValue95% CI
MK-8353 50 mg + Selumetinib 25 mg0.127± 74.6
MK-8353 100 mg + Selumetinib 50 mg0.174± 80.3
MK-8353 150 mg + Selumetinib 75 mg0.257± 47.5
Maximum Observed Plasma Concentration for MK-8353 Secondary · 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

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.

MK-8353, Cycle 1, Day 1
GroupValue95% CI
MK-8353 50 mg + Selumetinib 25 mg1.24± 138.4
MK-8353 100 mg + Selumetinib 50 mg1.65± 60.9
MK-8353 150 mg + Selumetinib 75 mg2.95± 62.3
MK-8353, Cycle 1, Day 4
GroupValue95% CI
MK-8353 50 mg + Selumetinib 25 mg1.87± 149.4
MK-8353 100 mg + Selumetinib 50 mg2.53± 51.5
MK-8353 150 mg + Selumetinib 75 mg3.61± 80.9
Cmax for Selumetinib Secondary · 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

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.

Selumetinib, Cycle 1,Day 1
GroupValue95% CI
MK-8353 50 mg + Selumetinib 25 mg1.01± 29.7
MK-8353 100 mg + Selumetinib 50 mg1.96± 91.1
MK-8353 150 mg + Selumetinib 75 mg3.37± 57.1
Selumetinib, Cycle 1, Day 4
GroupValue95% CI
MK-8353 50 mg + Selumetinib 25 mg1.04± 13.3
MK-8353 100 mg + Selumetinib 50 mg1.44± 123.6
MK-8353 150 mg + Selumetinib 75 mg2.37± 107.5

Adverse events — posted to ClinicalTrials.gov

Time frame: Non-serious adverse events (NSAEs): Up to ~45 weeks; Serious adverse events (SAEs): Up to ~45 weeks. All-cause mortality: Up to 24 months. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

MK-8353 50 mg + Selumetinib 25 mg
Serious: 0/3 (0%)
Deaths: 3/3
MK-8353 100 mg + Selumetinib 50 mg
Serious: 3/12 (25%)
Deaths: 8/12
MK-8353 150 mg + Selumetinib 75 mg
Serious: 4/15 (27%)
Deaths: 6/15

Serious adverse events (11 terms)

ReactionSystemMK-8353 50 mg + Selumetini…MK-8353 100 mg + Selumetin…MK-8353 150 mg + Selumetin…
VomitingGastrointestinal disorders
PneumoniaInfections and infestations
AnaemiaBlood and lymphatic system disorders
AscitesGastrointestinal disorders
DiarrhoeaGastrointestinal disorders
Duodenal obstructionGastrointestinal disorders
Large intestinal obstructionGastrointestinal disorders
Abdominal infectionInfections and infestations
SepsisInfections and infestations
DyspnoeaRespiratory, thoracic and mediastinal disorders
Pneumonia aspirationRespiratory, thoracic and mediastinal disorders
Other adverse events (103 terms — click to expand)

ReactionSystemMK-8353 50 mg + Selumetini…MK-8353 100 mg + Selumetin…MK-8353 150 mg + Selumetin…
DiarrhoeaGastrointestinal disorders
FatigueGeneral disorders
NauseaGastrointestinal disorders
Dermatitis acneiformSkin and subcutaneous tissue disorders
Abdominal painGastrointestinal disorders
ConstipationGastrointestinal disorders
VomitingGastrointestinal disorders
Blood creatine phosphokinase increasedInvestigations
Decreased appetiteMetabolism and nutrition disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
Alanine aminotransferase increasedInvestigations
Aspartate aminotransferase increasedInvestigations
CoughRespiratory, thoracic and mediastinal disorders
AnaemiaBlood and lymphatic system disorders
Retinal detachmentEye disorders
Vision blurredEye disorders
Visual impairmentEye disorders
Abdominal distensionGastrointestinal disorders
Dry mouthGastrointestinal disorders
DyspepsiaGastrointestinal disorders
Oedema peripheralGeneral disorders
DehydrationMetabolism and nutrition disorders
HypomagnesaemiaMetabolism and nutrition disorders
HypophosphataemiaMetabolism and nutrition disorders
ArthralgiaMusculoskeletal and connective tissue disorders
MyalgiaMusculoskeletal and connective tissue disorders
SciaticaNervous system disorders
InsomniaPsychiatric disorders
Dry skinSkin and subcutaneous tissue disorders
PruritusSkin and subcutaneous tissue disorders
LymphopeniaBlood and lymphatic system disorders
Atrial fibrillationCardiac disorders
External ear inflammationEar and labyrinth disorders
Dry eyeEye disorders
Eye irritationEye disorders
GlaucomaEye disorders
KeratitisEye disorders
Macular oedemaEye disorders
Periorbital oedemaEye disorders
RetinopathyEye disorders

Most-reported serious reactions: Vomiting, Pneumonia, Anaemia, Ascites, Diarrhoea, Duodenal obstruction, Large intestinal obstruction, Abdominal infection.

Data from ClinicalTrials.gov NCT03745989 adverse events section.

Sponsor's own description

This is a multicenter, worldwide, open-label study of MK-8353 in combination with selumetinib in participants with histologically or cytologically confirmed diagnosis of advanced solid tumor. This study will evaluate the safety, tolerability, and exploratory efficacy of MK-8353 in combination with selumetinib.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. RAS-targeted therapies: is the undruggable drugged?
    Moore AR, Rosenberg SC, McCormick F, Malek S. · · 2020 · cited 832× · PMID 32528145 · DOI 10.1038/s41573-020-0068-6
  2. The MAPK and AMPK signalings: interplay and implication in targeted cancer therapy.
    Yuan J, Dong X, Yap J, Hu J. · · 2020 · cited 388× · PMID 32807225 · DOI 10.1186/s13045-020-00949-4
  3. Targeting RAS-RAF-MEK-ERK signaling pathway in human cancer: Current status in clinical trials.
    Song Y, Bi Z, Liu Y, Qin F, et al · · 2023 · cited 129× · PMID 37013062 · DOI 10.1016/j.gendis.2022.05.006
  4. Oncogenic KRAS blockade therapy: renewed enthusiasm and persistent challenges.
    Tang D, Kroemer G, Kang R. · · 2021 · cited 65× · PMID 34607583 · DOI 10.1186/s12943-021-01422-7
  5. Development of small molecule extracellular signal-regulated kinases (ERKs) inhibitors for cancer therapy.
    Pan X, Pei J, Wang A, Shuai W, et al · · 2022 · cited 49× · PMID 35646548 · DOI 10.1016/j.apsb.2021.12.022
  6. Signaling pathways in liver cancer: pathogenesis and targeted therapy.
    Xue Y, Ruan Y, Wang Y, Xiao P, et al · · 2024 · cited 43× · PMID 38816668 · DOI 10.1186/s43556-024-00184-0
  7. <i>KRAS</i> mutation: The booster of pancreatic ductal adenocarcinoma transformation and progression.
    Zhang Z, Zhang H, Liao X, Tsai HI. · · 2023 · cited 31× · PMID 37152291 · DOI 10.3389/fcell.2023.1147676
  8. Targeting ERK beyond the boundaries of the kinase active site in melanoma.
    Sammons RM, Ghose R, Tsai KY, Dalby KN. · · 2019 · cited 29× · PMID 31190430 · DOI 10.1002/mc.23047

Verify or expand the search:

Other trials of MK-8353

Trials testing the same drug.

Other recruiting trials for Solid Tumors

Currently open trials in the same condition.

Other Merck Sharp & Dohme LLC trials

Trials by the same sponsor.

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Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT03745989.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing