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 preliminary efficacy of MK-8353
in combination with selumetinib.
- Have a histologically- or cytologically-documented, locally-advanced or metastatic
solid tumor by pathology report and have received, or been intolerant to, all
treatment known to confer clinical benefit.
- Provide an archival or newly obtained tumor tissue sample and blood samples for
assessment of proto-oncogene RAS/RAF mutation and for biomarker analysis.
- Have at least 1 measurable lesion as defined by Response Evaluation Criteria in Solid
Tumors Version 1.1 (RECIST 1.1) on imaging studies (computed tomography [CT] or
magnetic resonance imaging [MRI]) as assessed by the investigator/local radiology
- Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG)
Performance Scale. (Obtain within 7 days prior to first dose of study treatment.)
- Have the ability to swallow and retain oral medication.
- Demonstrate adequate organ function.
- Male participants must agree to use an acceptable contraception during the treatment
period and for at least 120 days after the last dose of study intervention and refrain
from donating sperm during this period.
- Female participants must not be pregnant, not breastfeeding, and either not a woman of
childbearing potential (WOCBP) or a WOCBP who agrees to follow the study's
contraceptive guidance during the treatment period and for at least 120 days, after
the last dose of study intervention.
- Have had chemotherapy, definitive radiation, or biological cancer therapy within 4
weeks (2 weeks for palliative radiation) prior to the first dose of study treatment,
or has not recovered to National Cancer Institute Common Terminology Criteria for
Adverse Events (CTCAE) Grade 1 or better from any AEs that were due to cancer
therapeutics administered more than 4 weeks earlier (this includes participants with
previous immunomodulatory therapy with residual immune-related AEs).
- Have clinically active central nervous system metastases and/or carcinomatous
- Have an active infection requiring therapy.
- Have known human immunodeficiency virus (HIV) and/or Hepatitis B or C infections, or
known to be positive for Hepatitis B antigen (HBsAg)/ Hepatitis B virus (HBV) DNA or
Hepatitis C Antibody or RNA.
- Have clinically significant cardiovascular disease as defined by study criteria.
- Have a history of thromboembolic or cerebrovascular events within 6 months prior to
treatment start, including transient ischemic attacks (TIAs), cerebrovascular
accidents (CVAs), deep vein thrombosis, or pulmonary embolism.
- Have neuromuscular disorders associated with an elevated creatine kinase (e.g.,
inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal
- Have one or more study-defined ophthalmological findings/conditions.
- Have a known history of Gilbert's Syndrome.
- Have a history or current evidence of a gastrointestinal (GI) condition (e.g.,
inflammatory bowel disease, Crohn's disease, ulcerative colitis) or impaired liver
function or diseases that in the opinion of the investigator may significantly alter
the absorption or metabolism of oral medications.
- Have a known psychiatric or substance abuse disorder, or any other cognitive disorder
that would interfere with the participant's ability to cooperate with the requirements
of the study.
- Is pregnant or breastfeeding, or expecting to conceive or father children within the
projected duration of the study, starting with the Screening Visit through 120 days
after the last dose of study treatment.
- Received prior therapy with a mitogen activated protein kinase (MEK) inhibitor (e.g.,
cobimetinib, trametinib), or an extracellular signal-regulated kinase (ERK) inhibitor
(e.g., MK-8353, GCD-0994, ulixertinib), or a proto-oncogene BRAF inhibitor (e.g.,
- Is currently participating and receiving study treatment in a study of an
investigational agent or has participated and received study treatment in a study of
an investigational agent or has used an investigational device within 28 days of
administration of selumetinib.
- Have a history of allergic reactions attributed to compounds of similar chemical or
biologic composition to agents and/or excipients used in the study.
- A WOCBP who has a positive urine pregnancy test within 24 hours before the first dose
of study treatment