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Advanced/Metastatic Solid TumorsPhase 1NCT03833427

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

A Phase 1 study testing Selumetinib and Pembrolizumab in people with Advanced/Metastatic Solid Tumors, run by Merck Sharp & Dohme LLC at 6 sites in 2 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Advanced/Metastatic Solid Tumors
What is being tested?
Selumetinib and Pembrolizumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
32 participants
Where
6 sitesin 2 countries
Study dates
18 Mar 2019to 28 Jun 2022
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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.
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  • 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.

Trial locations and contacts

6 sites in 2 countries.

6 sites in 2 countries

United States4 sites

  • City of Hope National Medical Center ( Site 0004)

    Duarte, California, 91010

  • START Midwest ( Site 0001)

    Grand Rapids, Michigan, 49546

  • John Theurer Cancer Center ( Site 0002)

    Hackensack, New Jersey, 07601

  • South Texas Accelerated Research Therapeutics, LLC (START) ( Site 0003)

    San Antonio, Texas, 78229

Other trials in United States

Canada2 sites

  • CHU de Quebec Universite de Laval ( Site 0013)

    Québec, Quebec, G1R 2J6

  • Princess Margaret Cancer Centre ( Site 0014)

    Toronto, Ontario, M5G 1Z5

Other trials in Canada

About this study

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.

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.

Being tested
Selumetinib, Pembrolizumab
Keywords
programmed cell death 1 (PD-1, PD1), programmed cell death ligand 1 (PD-L1, PDL1)
Medical subject headings
Parkinson Disease 4, Autosomal Dominant Lewy Body

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • SelumetinibDrug

    Also called MK-5618

    Selumetinib oral capsules administered BID at escalating dose levels. Selumetinib administered only in weeks 1\&2 of each 3-week treatment cycle.

  • PembrolizumabDrug

    Also called KEYTRUDA®, MK-3475

    Pembrolizumab administered by IV infusion at 200 mg Q3W, given on cycle day 1 of each 3-week treatment cycle.

Study groups in NCT03833427
Study groupRoleWhat they receive
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.
Receives: Drug: Selumetinib; Drug: 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.
Receives: Drug: Selumetinib; Drug: 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.
Receives: Drug: Selumetinib; Drug: 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.
Receives: Drug: Selumetinib; Drug: 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.
Receives: Drug: Selumetinib; Drug: 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.
Receives: Drug: Selumetinib; Drug: 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.
Receives: Drug: Selumetinib; Drug: Pembrolizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants Experiencing Dose-Limiting Toxicities (DLTs)

    DLT was defined as toxicities that: 1) were possibly, probably, or definitely related to study therapy, excluding toxicities clearly not related to the drug, such as disease progression, environmental factors, unrelated trauma; and 2) met pre-defined severity criteria. For each arm, the number of participants experiencing DLTs were assessed.

    Measured: Up to 21 days

  2. Number of Participants Who Experienced Adverse Event (AE)

    An AE was any unfavorable and unintended sign, symptom, or disease (new or exacerbated) in a clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. For each arm, the number of participants experiencing an AE will be assessed.

    Measured: Up to ~28 months

  3. Number of Participants Discontinuing Study Treatment Due to an Adverse Event

    An AE was any unfavorable and unintended sign, symptom, or disease (new or exacerbated) in a clinical study participant, temporally associated withthe use of study treatment, whether or not considered related to the study treatment. For each arm, the number of participants discontinuing study treatment due to an AE was assessed.

    Measured: Up to ~28 months

Secondary outcomes (3)

  1. Area Under the Concentration-Time Curve (AUC) of Selumetinib.

    Plasma selumetinib concentration was quantified for each arm to determine AUC, defined as the area under the concentration-time curve for selumetinib. AUC(0-last) is area under the concentration-time curve from dosing (time 0) to the time of the last measured concentration. AUC (0-12) is area under the concentration-time curve from dosing (time 0) to 12 hours.

    Measured: Pre-dose, 1, 2, 4, 6, between 8 and 12 hours post dose on Day 1; Time 0 pre-dose at Cycle 2 Day 1, Cycle 2 Day 14, Cycle 5 Day 1 and Cycle 5 Day 14.

  2. Maximum Observed Plasma Concentration (Cmax) of Selumetinib

    Plasma selumetinib concentration was quantified for each arm to determine Cmax, defined as the maximum observed concentration of selumetinib in plasma.

    Measured: Pre-dose, 1, 2, 4, 6, between 8 and 12 hours post dose on Day 1; Time 0 pre-dose at Cycle 2 Day 1, Cycle 2 Day 14, Cycle 5 Day 1 and Cycle 5 Day 14.

  3. Minimum Observed Plasma Concentration (Cmin) of Selumetinib

    Plasma selumetinib concentration was quantified for each arm to determine Cmin, defined as the minimum observed concentration of selumetinib in plasma.

    Measured: Pre-dose, 1, 2, 4, 6, between 8 and 12 hours post dose on Day 1; Time 0 pre-dose at Cycle 2 Day 1, Cycle 2 Day 14, Cycle 5 Day 1 and Cycle 5 Day 14.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Feb 2019
  2. Study start18 Mar 2019
  3. Primary completion28 Jun 2022
  4. Study completion28 Jun 2022

Why it stopped: Business Reasons

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
32 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03833427
Sponsor's protocol ID
5618-001
Other IDs
MK-5618-001
Status last verified
Nov 2024
First submitted
6 Feb 2019
Last updated
7 Nov 2024
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Publications

  • Chenard-Poirier M, Hansen AR, Gutierrez ME, Rasco D, Xing Y, Chen LC, Zhou H, Webber AL, Freshwater T, Sharma MR. A phase 1 trial of the MEK inhibitor selumetinib in combination with pembrolizumab for advanced or metastatic solid tumors. Invest New Drugs. 2024 Jun;42(3):241-251. doi: 10.1007/s10637-024-01428-0. Epub 2024 Mar 14.

    PubMed 38483782

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Selumetinib and Pembrolizumab in people with Advanced/Metastatic Solid Tumors, run by Merck Sharp & Dohme LLC at 6 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 7 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 30 Oct 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants Experiencing Dose-Limiting Toxicities (DLTs) (time frame: Up to 21 days). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03833427, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Nov 2024.

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