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Safety and Pharmacokinetics Study of MK-5890 as Monotherapy and in Combination With Pembrolizumab (MK-3475) in Adults With Advanced Solid Tumors (MK-5890-001)

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ClinicalTrials.gov Identifier: NCT03396445
Recruitment Status : Recruiting
First Posted : January 11, 2018
Last Update Posted : March 27, 2020
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Tracking Information
First Submitted Date  ICMJE January 4, 2018
First Posted Date  ICMJE January 11, 2018
Last Update Posted Date March 27, 2020
Actual Study Start Date  ICMJE February 18, 2018
Estimated Primary Completion Date October 6, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 23, 2019)
  • Arms 1 and 2: Dose-limiting Toxicities (DLTs) Graded Using National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 or Later [ Time Frame: Cycle 1 (Up to 21 days) ]
    A DLT is defined as any of the following toxicities, if assessed by the investigator to be related to study treatment:
    • Grade 4 nonhematologic toxicity;
    • Grade 4 hematologic toxicity lasting ≥7 days, except thrombocytopenia;
    • Grade 4 thrombocytopenia;
    • Grade 3 thrombocytopenia associated with bleeding that requires a platelet transfusion;
    • Nonhematologic adverse event (AE) Grade ≥3 in severity, with exceptions;
    • Grade 3 or 4 nonhematologic laboratory abnormality if: clinically significant medical intervention is required or if abnormality leads to hospitalization, persists for >1 week or results in drug-induced liver injury with exceptions;
    • Grade 3 or Grade 4 febrile neutropenia;
    • Prolonged delay (>2 weeks) in initiating Cycle 2 due to treatment-related toxicity;
    • Treatment-related toxicity resulting in participant study treatment discontinuation during Cycle 1;
    • Missing >25% of the MK-5890 dose during Cycle 1 resulting from treatment-related AE;
    • Grade 5 toxicity.
  • Arms 1 and 2: Number of Participants with Adverse Events (AEs) [ Time Frame: Up to 27 months ]
    An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants in Arms 1 and 2 who experience at least one AE will be presented.
  • Arms 1 and 2: Number of Study Treatment Discontinuations Due to an Adverse Event (AE) [ Time Frame: Up to 24 months ]
    The number of participants in Arms 1 and 2 who discontinue study treatment due to an AE will be presented.
Original Primary Outcome Measures  ICMJE
 (submitted: January 4, 2018)
  • Dose-limiting Toxicities (DLTs) Graded Using National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 or Later [ Time Frame: Cycle 1 (Up to 21 days) ]
    A DLT is defined as any of the following toxicities, if assessed by the investigator to be related to study treatment:
    • Grade 4 nonhematologic toxicity;
    • Grade 4 hematologic toxicity lasting ≥7 days, except thrombocytopenia;
    • Grade 4 thrombocytopenia;
    • Grade 3 thrombocytopenia associated with bleeding that requires a platelet transfusion;
    • Nonhematologic adverse event (AE) Grade ≥3 in severity, with exceptions;
    • Grade 3 or 4 nonhematologic laboratory abnormality if: clinically significant medical intervention is required or if abnormality leads to hospitalization, persists for >1 week or results in drug-induced liver injury with exceptions;
    • Grade 3 or Grade 4 febrile neutropenia;
    • Prolonged delay (>2 weeks) in initiating Cycle 2 due to treatment-related toxicity;
    • Treatment-related toxicity resulting in participant study treatment discontinuation during Cycle 1;
    • Missing >25% of the MK-5890 dose during Cycle 1 resulting from treatment-related AE;
    • Grade 5 toxicity.
  • Adverse Events (AEs) [ Time Frame: Up to 27 months ]
    An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants who experience at least one AE will be presented.
  • Study Treatment Discontinuations Due to an AE [ Time Frame: Up to 24 months ]
    The number of participants who discontinue study treatment due to an AE will be presented.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 23, 2019)
  • All Arms: Area Under the Concentration-Time Curve (AUC) of MK-5890 [ Time Frame: At designated time points (Up to 25 months) ]
    Blood samples will be obtained at designated time points for the assessment of MK-5890 AUC: Cycles 1-4: Day 1: Predose, (end of pembrolizumab infusion for participants receiving pembrolizumab), end of MK-5890 infusion, 2 hours post start of MK-5890 infusion, Days 2, 3, 5, 8 & 15: Once daily; Cycles 5, 6 & every 4 cycles thereafter: Day1: Predose; 30 days post last dose. Each cycle is 21 days. (Up to 25 months)
  • All Arms: Minimum Serum Concentration (Cmin) of MK-5890 [ Time Frame: At designated time points (Up to 25 months) ]
    Blood samples will be obtained at designated time points for the assessment of MK-5890 Cmin: Cycles 1-4: Day 1: Predose, (end of pembrolizumab infusion for participants receiving pembrolizumab), end of MK-5890 infusion, 2 hours post start of MK-5890 infusion, Days 2, 3, 5, 8 & 15: Once daily; Cycles 5, 6 & every 4 cycles thereafter: Day1: Predose; 30 days post last dose. Each cycle is 21 days. (Up to 25 months)
  • All Arms: Maximum Serum Concentration (Cmax) of MK-5890 [ Time Frame: At designated time points (Up to 25 months) ]
    Blood samples will be obtained at designated time points for the assessment of MK-5890 Cmax: Cycles 1-4: Day 1: Predose, (end of pembrolizumab infusion for participants receiving pembrolizumab), end of MK-5890 infusion, 2 hours post start of MK-5890 infusion, Days 2, 3, 5, 8 & 15: Once daily; Cycles 5, 6 & every 4 cycles thereafter: Day1: Predose; 30 days post last dose. Each cycle is 21 days. (Up to 25 months)
  • Arms 1 and 2: Objective Response Rate (ORR) Based on Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) [ Time Frame: Up to 24 months ]
    The ORR is defined as the percentage of participants who have a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1. The ORR of MK-5890 when used as monotherapy and in combination with pembrolizumab (Arms 1 and 2) as assessed by the investigator will be presented.
  • Arm 3: Dose-limiting Toxicities (DLTs) Graded Using National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 or Later [ Time Frame: Cycle 1 (Up to 21 days) ]
    A DLT is defined as any of the following toxicities, if assessed by the investigator to be related to study treatment:
    • Grade 4 nonhematologic toxicity;
    • Grade 4 hematologic toxicity lasting ≥7 days, except thrombocytopenia;
    • Grade 4 thrombocytopenia;
    • Grade 3 thrombocytopenia associated with bleeding that requires a platelet transfusion;
    • Nonhematologic adverse event (AE) Grade ≥3 in severity, with exceptions;
    • Grade 3 or 4 nonhematologic laboratory abnormality if: clinically significant medical intervention is required or if abnormality leads to hospitalization, persists for >1 week or results in drug-induced liver injury with exceptions;
    • Grade 3 or Grade 4 febrile neutropenia;
    • Prolonged delay (>2 weeks) in initiating Cycle 2 due to treatment-related toxicity;
    • Treatment-related toxicity resulting in participant study treatment discontinuation during Cycle 1;
    • Missing >25% of the MK-5890 dose during Cycle 1 resulting from treatment-related AE;
    • Grade 5 toxicity.
  • Arm 3: Number of Participants with Adverse Events (AEs) [ Time Frame: Up to 27 months ]
    An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants in Arm 3 who experience at least one AE will be presented.
  • Arm 3: Number of Study Treatment Discontinuations Due to an Adverse Event (AE) [ Time Frame: Up to 24 months ]
    The number of participants in Arm 3 who discontinue study treatment due to an AE will be presented.
Original Secondary Outcome Measures  ICMJE
 (submitted: January 4, 2018)
  • Area Under the Concentration-Time Curve (AUC) of MK-5890 When Administered as Monotherapy and in Combination with Pembrolizumab [ Time Frame: At designated time points (Up to 25 months) ]
    Blood samples will be obtained at designated time points for the assessment of MK-5890 AUC: Cycles 1-4: Day 1: Predose, (end of pembrolizumab infusion for participants receiving pembrolizumab), end of MK-5890 infusion, 2 hours post start of MK-5890 infusion, Days 2, 3, 5, 8 & 15: Once daily; Cycles 5, 6 & every 4 cycles thereafter: Day1: Predose; 30 days post last dose. (Up to 25 months)
  • Minimum Serum Concentration (Cmin) of MK-5890 When Administered as Monotherapy and in Combination with Pembrolizumab [ Time Frame: At designated time points (Up to 25 months) ]
    Blood samples will be obtained at designated time points for the assessment of MK-5890 Cmin: Cycles 1-4: Day 1: Predose, (end of pembrolizumab infusion for participants receiving pembrolizumab), end of MK-5890 infusion, 2 hours post start of MK-5890 infusion, Days 2, 3, 5, 8 & 15: Once daily; Cycles 5, 6 & every 4 cycles thereafter: Day1: Predose; 30 days post last dose. (Up to 25 months)
  • Maximum Serum Concentration (Cmin) of MK-5890 When Administered as Monotherapy and in Combination with Pembrolizumab [ Time Frame: At designated time points (Up to 25 months) ]
    Blood samples will be obtained at designated time points for the assessment of MK-5890 Cmax: Cycles 1-4: Day 1: Predose, (end of pembrolizumab infusion for participants receiving pembrolizumab), end of MK-5890 infusion, 2 hours post start of MK-5890 infusion, Days 2, 3, 5, 8 & 15: Once daily; Cycles 5, 6 & every 4 cycles thereafter: Day1: Predose; 30 days post last dose. (Up to 25 months)
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety and Pharmacokinetics Study of MK-5890 as Monotherapy and in Combination With Pembrolizumab (MK-3475) in Adults With Advanced Solid Tumors (MK-5890-001)
Official Title  ICMJE A Phase 1 Study of MK-5890 as Monotherapy and in Combination With Pembrolizumab in Participants With Advanced Solid Tumors
Brief Summary The purpose of this study is to assess the safety and pharmacokinetics of MK-5890 when administered alone and in combination with pembrolizumab (MK-3475) in adults with advanced solid tumors. The initial course of MK-5890 monotherapy or MK-5890 plus pembrolizumab combination therapy will be for up to 35 administrations (approximately 2 years). The safety and pharmacokinetics of MK-5890 when administered with pembrolizumab, pemetrexed and carboplatin will also be assessed in adults with non-squamous non-small cell lung cancer (NSCLC).
Detailed Description Participants receiving MK-5890 monotherapy who experience disease progression may be eligible to switch to receiving MK-5890 plus pembrolizumab combination therapy for up to 35 cycles (approximately 2 years) at the discretion of the Investigator and approval of the Sponsor.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Pharmacokinetics
  • Solid Tumor
Intervention  ICMJE
  • Drug: MK-5890
    IV infusion
  • Biological: Pembrolizumab
    IV infusion
    Other Name: MK-3475
  • Drug: Pemetrexed
    IV infusion
    Other Name: ALIMTA®
  • Drug: Carboplatin
    IV infusion
    Other Name: PARAPLATIN®
Study Arms  ICMJE
  • Experimental: Arm 1: MK-5890
    Participants receive escalating doses of MK-5890 via intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years).
    Intervention: Drug: MK-5890
  • Experimental: Arm 2: MK-5890 + Pembrolizumab
    Participants receive escalating doses of MK-5890 via IV infusion on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years) PLUS pembrolizumab 200 mg via IV infusion on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years).
    Interventions:
    • Drug: MK-5890
    • Biological: Pembrolizumab
  • Experimental: Arm 3: MK-5890 + Pembrolizumab + Pemetrexed + Carboplatin
    Participants receive MK-5890 at the selected dose via IV infusion PLUS pembrolizumab 200 mg via IV infusion PLUS pemetrexed 500 mg/m^2 via IV infusion PLUS carboplatin Area Under the Curve (AUC) 5 mg/mL/min via IV infusion, all given on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years).
    Interventions:
    • Drug: Pemetrexed
    • Drug: Carboplatin
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: July 23, 2019)
162
Original Estimated Enrollment  ICMJE
 (submitted: January 4, 2018)
88
Estimated Study Completion Date  ICMJE October 6, 2022
Estimated Primary Completion Date October 6, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Arms 1 & 2: Histologically or cytologically confirmed advanced/metastatic solid tumor by pathology report and has received or been intolerant to all treatment known to confer clinical benefit.
  • Arm 3: Histologically or cytologically confirmed diagnosis of stage IV (M1a or M1b per current American Joint Committee on Cancer criteria) non-squamous NSCLC.
  • Measureable disease by RECIST 1.1. as assessed by the local site investigator/radiologist. Target lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
  • Adequate organ function.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  • Male participants must agree to use adequate contraception during the treatment period and for at least 120 days after the last dose of MK-5890 or pembrolizumab OR 180 days after the last dose of chemotherapeutic agents and refrain from donating sperm during this period.
  • Female participants must not be pregnant or breast feeding and agree to follow use adequate contraception during the treatment period and for at least 120 days after the last dose of MK-5890 or pembrolizumab OR 180 days after the last dose of chemotherapeutic agents.
  • Submit an evaluable baseline tumor sample for analysis (either a newly obtained or archival tumor sample).

Exclusion Criteria:

  • History of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years.
  • Clinically active central nervous system metastases and/or carcinomatous meningitis.
  • Has had a severe hypersensitivity reaction to treatment with a monoclonal antibody (mAb) and/or other components of the study treatment.
  • Active infection requiring systemic treatment.
  • History of interstitial lung disease.
  • History of (noninfectious) pneumonitis that required steroids or current pneumonitis.
  • Symptomatic ascites or pleural effusion.
  • Previously had a stem cell or bone marrow transplant.
  • Previously had a solid organ transplant.
  • Active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs) except vitiligo or resolved childhood asthma/atopy.
  • Known human immunodeficiency virus (HIV) and/or active and acute Hepatitis B or C infections.
  • Not fully recovered from any effects of major surgery without significant detectable infection.
  • Pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study.
  • Had chemotherapy, definitive radiation, or biological cancer therapy within 4 weeks (2 weeks for palliative radiation) before the first dose of study treatment, or has not recovered to Grade ≤1 or better from any AEs that were due to cancer therapeutics administered more than 4 weeks earlier.
  • Expected to require any other form of antineoplastic therapy while participating in this study.
  • On chronic systemic steroid therapy in excess of replacement doses (e.g., exceeding 10 mg/day of prednisone equivalent), or on any other form of immunosuppressive medication.
  • Regular user (including "recreational use") of any illicit drugs at the time of signing informed consent, or has a recent history (within the last year) of substance abuse (including alcohol), as determined by the treating investigator. Participants who use cannabis for medicinal purposes or to treat specific symptoms will not be excluded unless it is being abused in the opinion of the treating investigator.
  • Received a live-virus vaccine within 28 days before the first dose of study treatment.
  • 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 before the first dose of study treatment.

Additional Exclusion Criteria for Participants in Arm 3:

  • Has received radiation therapy to the lung that is >30 Gray (Gy) within 6 months before the first dose of study treatment.
  • Is unable to interrupt aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs), other than an aspirin dose ≤1.3 g per day, for a 5-day period (8-day period for long-acting agents, such as piroxicam).
  • Is unable or unwilling to take folic acid or vitamin B12 supplementation.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Toll Free Number 1-888-577-8839 Trialsites@merck.com
Listed Location Countries  ICMJE Israel,   Netherlands,   Spain,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03396445
Other Study ID Numbers  ICMJE 5890-001
MK-5890-001 ( Other Identifier: Merck Protocol Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
URL: http://engagezone.msd.com/ds_documentation.php
Responsible Party Merck Sharp & Dohme Corp.
Study Sponsor  ICMJE Merck Sharp & Dohme Corp.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Medical Director Merck Sharp & Dohme Corp.
PRS Account Merck Sharp & Dohme Corp.
Verification Date March 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP