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

NCT ID: NCT03745989

Last Updated: 2023-07-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-02-22
• Study Completion Date: 2021-03-19

Brief Summary

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.

Detailed Description

As specified by Phase 1 protocol-flexible language, modifications to the dose or dosing regimen can be made to achieve the scientific goals of the trial objectives and/or ensure appropriate safety of the trial participants. The proposed doses may be adjusted based on evaluation of safety, tolerability, and pharmacokinetic data.

Conditions

Solid Tumors

Study Design

• Allocation Method: NA
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

MK-8353 and Selumetinib Dose Escalation

Participants will receive a combination MK-8353 and selumetinib for 4 days on and 3 days off until disease progression or discontinuation. MK-8353 will be escalated sequentially from 50 mg to 250 mg based on pharmacokinetic and safety data. Selumetinib will be escalated sequentially from 25 mg to 75 mg based on pharmacokinetic and safety data. Doses may be adjusted downward sequentially based on tolerability

Group Type: EXPERIMENTAL

MK-8353

Intervention Type: DRUG

Participants will receive MK-8353 orally twice daily (BID), escalated sequentially from 50 mg to 250 mg.

Selumetinib

Intervention Type: DRUG

Participants will receive selumetinib orally BID, escalated sequentially from 25 mg to 75 mg.

Interventions

MK-8353

Participants will receive MK-8353 orally twice daily (BID), escalated sequentially from 50 mg to 250 mg.

Intervention Type: DRUG

Selumetinib

Participants will receive selumetinib orally BID, escalated sequentially from 25 mg to 75 mg.

Intervention Type: DRUG

Other Intervention Names

MK-5618

Eligibility Criteria

Inclusion Criteria

• 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 rat sarcoma virus (RAS)/rapidly accelerated fibrosarcoma (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 review.
• 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.

Exclusion Criteria

• 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 meningitis.
• 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) deoxyribonucleic acid (DNA) or Hepatitis C Antibody or ribonucleic acid (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 muscular atrophy).
• 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., dabrafenib, vemurafenib).
• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

Locations

Florida Cancer Specialists ( Site 7000)

Sarasota, Florida, United States

Next Oncology ( Site 0001)

San Antonio, Texas, United States

BC Cancer-Vancouver Center ( Site 0011)

Vancouver, British Columbia, Canada

Princess Margaret Cancer Centre ( Site 0012)

Toronto, Ontario, Canada

Istituto Oncologica della Svizzera Italiana (IOSI) ( Site 0020)

Bellinzona, Canton Ticino, Switzerland

Countries

United States; Canada; Switzerland

References

Stathis A, Tolcher AW, Wang JS, Renouf DJ, Chen LC, Suttner LH, Freshwater T, Webber AL, Nayak T, Siu LL. Results of an open-label phase 1b study of the ERK inhibitor MK-8353 plus the MEK inhibitor selumetinib in patients with advanced or metastatic solid tumors. Invest New Drugs. 2023 Jun;41(3):380-390. doi: 10.1007/s10637-022-01326-3. Epub 2023 Apr 11.

Reference Type: RESULT

PMID: 37040046 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

http://merckoncologyclinicaltrials.com

Merck Oncology Clinical Trials Information

Other Identifiers

MK-8353-014

Identifier Type: OTHER

Identifier Source: secondary_id

8353-014

Identifier Type: -

Identifier Source: org_study_id