Clinical Trials /

Study of Selumetinib (MK-5618) in Combination With Pembrolizumab (MK-3475) in Participants With Advanced/Metastatic Solid Tumors (MK-5618-001)

NCT03833427

Description:

This study will examine the safety, pharmacokinetics, and efficacy of escalating doses of selumetinib (MK-5618) in combination with intravenous (IV) pembrolizumab (MK-3475) for participants with advanced / metastatic solid tumors.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Study of Selumetinib (MK-5618) in Combination With Pembrolizumab (MK-3475) in Participants With Advanced/Metastatic Solid Tumors (MK-5618-001)
  • Official Title: A Phase 1b Multi-center Clinical Study of Selumetinib (MK-5618) in Combination With Pembrolizumab (MK-3475) in Participants With Advanced/Metastatic Solid Tumors.

Clinical Trial IDs

  • ORG STUDY ID: 5618-001
  • SECONDARY ID: MK-5618-001
  • NCT ID: NCT03833427

Conditions

  • Advanced/Metastatic Solid Tumors

Interventions

DrugSynonymsArms
SelumetinibMK-5618Selumetinib at Dose Level 1 + Pembrolizumab
PembrolizumabKEYTRUDA®, MK-3475Selumetinib at Dose Level 1 + Pembrolizumab

Purpose

This study will examine the safety, pharmacokinetics, and efficacy of escalating doses of selumetinib (MK-5618) in combination with intravenous (IV) pembrolizumab (MK-3475) for participants with advanced / metastatic solid tumors.

Trial Arms

NameTypeDescriptionInterventions
Selumetinib at Dose Level 1 + PembrolizumabExperimentalParticipants receive 200 mg pembrolizumab (IV infusion; every three weeks [Q3W]) in combination with selumetinib at dose level 1 (dosed orally; twice daily [BID]) for up to 35 treatment cycles (cycle length: 3 weeks). During each 3-week cycle, selumetinib will be administered only for the first two weeks.
  • Selumetinib
  • Pembrolizumab
Selumetinib at Dose Level 2 + PembrolizumabExperimentalParticipants receive 200 mg pembrolizumab (IV infusion; Q3W) in combination with selumetinib at dose level 2 (dosed orally; BID) for up to 35 treatment cycles (cycle length: 3 weeks). During each 3-week cycle, selumetinib will be administered only for the first two weeks.
  • Selumetinib
  • Pembrolizumab
Selumetinib at Dose Level 3 + PembrolizumabExperimentalParticipants receive 200 mg pembrolizumab (IV infusion; Q3W) in combination with selumetinib at dose level 3 (dosed orally; BID) for up to 35 treatment cycles (cycle length: 3 weeks). During each 3-week cycle, selumetinib will be administered only for the first two weeks.
  • Selumetinib
  • Pembrolizumab
Selumetinib at Dose Level 4 + PembrolizumabExperimentalParticipants receive 200 mg pembrolizumab (IV infusion; Q3W) in combination with selumetinib at dose level 4 (dosed orally; BID) for up to 35 treatment cycles (cycle length: 3 weeks). During each 3-week cycle, selumetinib will be administered only for the first two weeks.
  • Selumetinib
  • Pembrolizumab
Selumetinib at Dose Level 5 + PembrolizumabExperimentalParticipants receive 200 mg pembrolizumab (IV infusion; Q3W) in combination with selumetinib at dose level 5 (dosed orally; BID) for up to 35 treatment cycles (cycle length: 3 weeks). During each 3-week cycle, selumetinib will be administered only for the first two weeks.
  • Selumetinib
  • Pembrolizumab
Selumetinib at Dose Level 6 + PembrolizumabExperimentalParticipants receive 200 mg pembrolizumab (IV infusion; Q3W) in combination with selumetinib at dose level 6 (dosed orally; BID) for up to 35 treatment cycles (cycle length: 3 weeks). During each 3-week cycle, selumetinib will be administered only for the first two weeks.
  • Selumetinib
  • Pembrolizumab
Selumetinib at Dose Level 7 + PembrolizumabExperimentalParticipants receive 200 mg pembrolizumab (IV infusion; Q3W) in combination with selumetinib at dose level 7 (dosed orally; BID) for up to 35 treatment cycles (cycle length: 3 weeks). During each 3-week cycle, selumetinib will be administered only for the first two weeks.
  • Selumetinib
  • Pembrolizumab

Eligibility Criteria

        Inclusion Criteria:

          -  Has a histologically or cytologically confirmed advanced or metastatic solid tumor by
             pathology report and have received, or been intolerant to, all treatment known to
             confer clinical benefit.

          -  Has measurable disease by Response Evaluation Criteria in Solid Tumors, Version 1.1
             (RECIST 1.1) as assessed by local site investigator/radiology. Target lesions situated
             in a previously irradiated area are considered measurable if progression has been
             demonstrated in such lesions.

          -  Has a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG)
             Performance Scale.

          -  Is able to swallow and retain oral medication and has no clinically significant
             gastrointestinal abnormalities that might alter absorption.

          -  Has adequate organ function.

          -  If male, agree to use a 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.

          -  If female, is not pregnant or breastfeeding, and is not a woman of childbearing
             potential (WOCBP). If a WOCBP, agree to follow the contraceptive guidance during the
             treatment period and for at least 120 days after the last dose of study intervention.

          -  For Human immunodeficiency virus (HIV) infected participants, must have well
             controlled HIV on a stable regimen of anti-retroviral therapy (ART). Participants on
             ART must have been without changes in drugs or dose modification for at least 4 weeks
             prior to study entry.

        Exclusion Criteria:

          -  Has 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 Common Toxicity 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). Participants receiving ongoing replacement hormone
             therapy for endocrine immune-related AEs will not be excluded from participation in
             this study.

          -  Has clinically active central nervous system metastases and/or carcinomatous
             meningitis.

          -  Has had a severe hypersensitivity reaction (≥ Grade 3) to treatment with a monoclonal
             antibody/component of the study treatment, and/or has a history of allergic reactions
             attributed to compounds of similar chemical or biologic composition to agents and/or
             excipients used in the study.

          -  Has an active infection requiring therapy.

          -  Has a history of (non-infectious) pneumonitis that required steroids or has current
             pneumonitis.

          -  Has an active autoimmune disease that has required systemic treatment in the past 2
             years except vitiligo or resolved childhood asthma/atopy. Replacement therapy, such as
             thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or
             pituitary insufficiency, is not considered a form of systemic treatment and is
             allowed. Use of non-systemic steroids is permitted.

          -  Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any
             other form of immunosuppressive therapy within 7 days prior to allocation.

          -  Has known Hepatitis B or C infection.

          -  For HIV infected participants, has a history of Kaposi's sarcoma and/or Multicentric
             Castleman's Disease.

          -  Has undergone major surgery and has not recovered adequately from any toxicity and/or
             complications from the intervention prior to starting study therapy.

          -  Has baseline peripheral neuropathy/paresthesia Grade 1.

          -  Has any medical, psychiatric, cognitive, or other condition that may compromise the
             participant's ability to understand the participant information, give informed
             consent, comply with the study protocol, or complete the study, in the opinion of the
             treating investigator.

          -  Participants with clinically significant cardiovascular disease as defined by the
             following: 1) Uncontrolled hypertension; 2) Left ventricular ejection fraction (LVEF)
             <55%; 3) Symptomatic heart failure (New York Heart Association (NYHA) Grade II to IV),
             prior or current cardiomyopathy, or severe valvular heart disease; 4) Uncontrolled
             angina; 5) Clinically significant cardiac arrhythmia and/or conduction abnormality ≤6
             months prior to start of study treatment; 6) Myocardial infarction or acute coronary
             syndrome ≤6 months prior to start of study treatment; 7) Mean QT interval calculated
             according to the Frederica method (QTcF) interval: Male >450 ms; Female >470 ms.

          -  Has a history of thromboembolic or cerebrovascular event(s) within 6 months prior to
             study enrollment, including transient ischemic attack, cerebrovascular accident, deep
             vein thrombosis, or pulmonary embolism.

          -  Has a neuromuscular disorder associated with an elevated creatine kinase (e.g.,
             inflammatory myopathy, muscular dystrophy, amyotrophic lateral sclerosis, spinal
             muscular atrophy.

          -  Has a history of, or current, retinal vein occlusion (RVO) or current risk factors for
             RVO (e.g., uncontrolled glaucoma, ocular hypertension, history of hyperviscosity, or
             hypercoagulability syndromes).

          -  Has retinal degenerative disease.

          -  Has a history or current evidence of any condition, therapy, or laboratory abnormality
             that might confound the results of the study, interfere with the participant's
             participation for the full duration of the study, make administration of the study
             treatments hazardous or make it difficult to monitor adverse effects such that it is
             not in the best interest of the participant to participate, in the opinion of the
             treating investigator.

          -  Has a known psychiatric or substance abuse 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.

          -  Has received a live-virus vaccine within 28 days of planned treatment start. Seasonal
             flu vaccines that do not contain live virus are permitted.

          -  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.

          -  Is a WOCBP who has a positive urine pregnancy test within 24 hours before the first
             dose of study treatment.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of Participants Experiencing Dose-Limiting Toxicities (DLTs)
Time Frame:Up to Day 21 of Cycle 1 (each cycle is 21 days)
Safety Issue:
Description:DLTs are defined as toxicities that: 1) are possibly, probably, or definitely related to study therapy; and 2) meet pre-defined severity criteria. For each arm, the number of participants experiencing DLTs will be assessed.

Secondary Outcome Measures

Measure:Area Under the Concentration-Time Curve (AUC) of Selumetinib
Time Frame:[Cycle 1]: At designated time points; up to 3 weeks (each cycle is 21 days)
Safety Issue:
Description:Plasma selumetinib concentration will be quantified for each arm to determine AUC, defined as the area under the concentration-time curve for selumetinib.
Measure:Maximum Observed Plasma Concentration (Cmax) of Selumetinib
Time Frame:[Cycle 1]: At designated time points; up to 3 weeks (each cycle is 21 days)
Safety Issue:
Description:Plasma selumetinib concentration will be quantified for each arm to determine Cmax, defined as the maximum observed concentration of selumetinib in plasma.
Measure:Minimum Observed Plasma Concentration (Cmin) of Selumetinib
Time Frame:[Cycles 1 to 5]: At designated time points; up to 15 weeks (each cycle is 21 days)
Safety Issue:
Description:Plasma selumetinib concentration will be quantified for each arm to determine Cmin, defined as the minimum observed concentration of selumetinib in plasma.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Merck Sharp & Dohme Corp.

Trial Keywords

  • programmed cell death 1 (PD-1, PD1)
  • programmed cell death ligand 1 (PD-L1, PDL1)

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