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

NCT03833427 | Terminated Phase 1 Results FDA Drug

• 2 other identifiers: 5618-001MK-5618-001
• Study Type: interventional
• Target: 32
• Locations: 2 countries
• Sites: 6

Brief 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.

Conditions

Advanced/Metastatic Solid Tumors

Keywords

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

Outcome Measures

Primary Outcomes (3)

• 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.

  Up to 21 days

• 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.

  Up to ~28 months

• 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.

  Up to ~28 months

Secondary Outcomes (3)

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

  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.

• Maximum Observed Plasma Concentration (Cmax) of Selumetinib

  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.

• Minimum Observed Plasma Concentration (Cmin) of Selumetinib

  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.

Study Arms (7)

Selumetinib at Dose Level 1 + Pembrolizumab

EXPERIMENTAL

Participants 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.

Drug: Selumetinib; Drug: Pembrolizumab

Selumetinib at Dose Level 2 + Pembrolizumab

EXPERIMENTAL

Participants 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.

Drug: Selumetinib; Drug: Pembrolizumab

Selumetinib at Dose Level 3 + Pembrolizumab

EXPERIMENTAL

Participants 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.

Drug: Selumetinib; Drug: Pembrolizumab

Selumetinib at Dose Level 4 + Pembrolizumab

EXPERIMENTAL

Participants 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.

Drug: Selumetinib; Drug: Pembrolizumab

Selumetinib at Dose Level 5 + Pembrolizumab

EXPERIMENTAL

Participants 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.

Drug: Selumetinib; Drug: Pembrolizumab

Selumetinib at Dose Level 6 + Pembrolizumab

EXPERIMENTAL

Participants 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.

Drug: Selumetinib; Drug: Pembrolizumab

Selumetinib at Dose Level 7 + Pembrolizumab

EXPERIMENTAL

Participants 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.

Drug: Selumetinib; Drug: Pembrolizumab

Interventions

Selumetinib DRUG

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

Also known as: MK-5618

Selumetinib at Dose Level 1 + Pembrolizumab; Selumetinib at Dose Level 2 + Pembrolizumab; Selumetinib at Dose Level 3 + Pembrolizumab; Selumetinib at Dose Level 4 + Pembrolizumab; Selumetinib at Dose Level 5 + Pembrolizumab; Selumetinib at Dose Level 6 + Pembrolizumab; Selumetinib at Dose Level 7 + Pembrolizumab

Pembrolizumab DRUG

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

Also known as: KEYTRUDA®, MK-3475

Selumetinib at Dose Level 1 + Pembrolizumab; Selumetinib at Dose Level 2 + Pembrolizumab; Selumetinib at Dose Level 3 + Pembrolizumab; Selumetinib at Dose Level 4 + Pembrolizumab; Selumetinib at Dose Level 5 + Pembrolizumab; Selumetinib at Dose Level 6 + Pembrolizumab; Selumetinib at Dose Level 7 + Pembrolizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (6)

City of Hope National Medical Center ( Site 0004)

Duarte, California, 91010, United States

Location

START Midwest ( Site 0001)

Grand Rapids, Michigan, 49546, United States

Location

John Theurer Cancer Center ( Site 0002)

Hackensack, New Jersey, 07601, United States

Location

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

San Antonio, Texas, 78229, United States

Location

Princess Margaret Cancer Centre ( Site 0014)

Toronto, Ontario, M5G 1Z5, Canada

Location

CHU de Quebec Universite de Laval ( Site 0013)

Québec, Quebec, G1R 2J6, Canada

Location

Related Publications (1)

• 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.

  PMID: 38483782 RESULT

Related Links

• Merck Oncology Clinical Trials Information

MeSH Terms

Conditions

Parkinson Disease 4, Autosomal Dominant Lewy Body

Interventions

AZD 6244; pembrolizumab

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme LLC

ClinicalTrialsDisclosure@msd.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 6, 2019
• First Posted: February 7, 2019
• Study Start: March 18, 2019
• Primary Completion: June 28, 2022
• Study Completion: June 28, 2022
• Last Updated: November 7, 2024
• Results First Posted: October 30, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will share

Locations

CA (2); US (4)