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Study of MK-4830 as Monotherapy and in Combination With Pembrolizumab (MK-3475) in Participants With Advanced Solid Tumors (MK-4830-001)

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ClinicalTrials.gov Identifier: NCT03564691
Recruitment Status : Recruiting
First Posted : June 21, 2018
Last Update Posted : September 10, 2018
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Brief Summary:
This study will determine the safety and tolerability and to establish a preliminary recommended Phase 2 dose of MK-4830 administered as monotherapy and in combination with pembrolizumab (MK-3475) in adults with advance solid tumors.

Condition or disease Intervention/treatment Phase
Neoplasms Drug: MK-4830 Drug: Pembrolizumab Phase 1

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 70 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1 Open Label, Multi-Arm, Multicenter Study of MK-4830 as Monotherapy and in Combination With Pembrolizumab for Participants With Advanced Solid Tumors
Actual Study Start Date : July 11, 2018
Estimated Primary Completion Date : July 27, 2022
Estimated Study Completion Date : July 27, 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Part A: MK-4830 Monotherapy
MK-4830 monotherapy (with MK-4830 doses determined by an accelerated titration design [ATD]) will be administered intravenously (IV), every 3 weeks (Q3W), starting with Cycle 1, Day 1, for a maximum of 35 cycles. Each cycle is 21 days.
Drug: MK-4830
MK-4830 will be administered intravenously (IV) Q3W. In Part C, MK-4830 will be administered after completion of pembrolizumab infusion. Dose escalation will proceed based on emerging safety and tolerability data of MK-4830 as monotherapy (Part A and B) and as combination therapy with pembrolizumab (Part C). For each dose level, an assessment will be made of the safety and tolerability data in order to define the next dose level to be tested.

Experimental: Part B: MK-4830 Monotherapy
MK-4830 monotherapy (with MK 4830 doses determined by a modified toxicity probability interval [mTPI] method) will be administered IV, Q3W, starting with Cycle 1, Day 1, for a maximum of 35 cycles. Each cycle is 21 days.
Drug: MK-4830
MK-4830 will be administered intravenously (IV) Q3W. In Part C, MK-4830 will be administered after completion of pembrolizumab infusion. Dose escalation will proceed based on emerging safety and tolerability data of MK-4830 as monotherapy (Part A and B) and as combination therapy with pembrolizumab (Part C). For each dose level, an assessment will be made of the safety and tolerability data in order to define the next dose level to be tested.

Experimental: Part C: MK-4830 and Pembrolizumab
Combination therapy with MK-4830 and pembrolizumab (with MK-4830 doses determined by an mTPI design). MK-4830 will be administered IV, Q3W, starting with Cycle 1 following pembrolizumab infusion, Day 1, for a maximum of 35 cycles. Each cycle is 21 days. Pembrolizumab will be administered by IV, Q3W, starting with Cycle 1, Day 1. Each cycle is 21 days. The combination may be administered for a maximum of 35 cycles.
Drug: MK-4830
MK-4830 will be administered intravenously (IV) Q3W. In Part C, MK-4830 will be administered after completion of pembrolizumab infusion. Dose escalation will proceed based on emerging safety and tolerability data of MK-4830 as monotherapy (Part A and B) and as combination therapy with pembrolizumab (Part C). For each dose level, an assessment will be made of the safety and tolerability data in order to define the next dose level to be tested.

Drug: Pembrolizumab
Pembrolizumab will be dosed at 200 mg IV Q3W - Part C only.
Other Name: MK-3475




Primary Outcome Measures :
  1. Dose-Limiting Toxicities (DLTs) [ Time Frame: Cycle 1 (Up to 21 days) ]

    The occurrence of the following toxicities, if assessed by the investigator to be possibly, probably, or definitely related to study treatment administration:

    • Grade 4 nonhematologic toxicity (not laboratory)
    • Grade 4 hematologic toxicity lasting >=7 days, except thrombocytopenia:
    • Any nonhematologic AE >=Grade 3 in severity, with exceptions
    • Any Grade 3 or Grade 4 alanine aminotransferase, aspartate aminotransferase, and/or bilirubin laboratory value
    • Any other nonhematologic laboratory value if:

    Clinically significant medical intervention is required to treat the participant, OR The abnormality leads to hospitalization, OR The abnormality persists for >1 week, OR The abnormality results in a drug-induced liver injury

    • Febrile neutropenia Grade 3 or Grade 4
    • Prolonged delay (>2 weeks) in initiating Cycle 2 due to treatment-related toxicity.
    • Any treatment-related toxicity that causes the participant to discontinue treatment during Cycle 1.
    • Grade 5 toxicity

  2. Adverse Events (AEs) [ Time Frame: Up to approximately 27 months ]
    Number of participants who experienced an AE. An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.

  3. Study Treatment Discontinuations Due to AEs [ Time Frame: Up to approximately 24 months ]
    Number of participants who discontinue from treatment due to an AE. An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.


Secondary Outcome Measures :
  1. Area Under the Curve (AUC) of Plasma MK-4830 [ Time Frame: 24 hours pre-infusion and end of infusion on Day 1 of Cycles 1 to 4, 6, and 8, and every 4 cycles thereafter and 2 hours post-infusion on Day 1 of Cycles 1 to 4, 6, and 8 and on Days 8 and Day 15 in Cycles 1 to 3 (Up to approximately 24 months) ]
    Pharmacokinetic (PK) parameter: area under the drug concentration/time curve

  2. Minimum Drug Concentration (Cmin) of Plasma MK-4830 [ Time Frame: 24 hours pre-infusion and end of infusion on Day 1 of Cycles 1 to 4, 6, and 8, and every 4 cycles thereafter and 2 hours post-infusion on Day 1 of Cycles 1 to 4, 6, and 8 and on Days 8 and Day 15 in Cycles 1 to 3 (Up to approximately 24 months) ]
    PK parameter: minimum drug concentration

  3. Maximum Drug Concentration (Cmax) of Plasma MK-4830 [ Time Frame: 24 hours pre-infusion and end of infusion on Day 1 of Cycles 1 to 4, 6, and 8, and every 4 cycles thereafter and 2 hours post-infusion on Day 1 of Cycles 1 to 4, 6, and 8 and on Days 8 and Day 15 in Cycles 1 to 3 (Up to approximately 24 months) ]
    PK parameter: maximum drug concentration



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Has any histologically- or cytologically-confirmed advanced/metastatic solid tumor by pathology report and have received, have been intolerant to, or have been ineligible for all treatment known to confer clinical benefit. Solid tumors of any type are eligible for enrollment.
  • Has measurable disease by Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST 1.1) as assessed by the local site investigator/radiology.
  • Submits an evaluable baseline tumor sample for analysis (either a recent or archival tumor sample).
  • Has 1 or more discrete malignant lesions that are amenable to biopsy
  • Has a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale.
  • Demonstrates adequate organ function
  • A male participant must agree to use an approved contraception(s) during the treatment period and for at least 180 days after the last dose of study treatment and refrain from donating sperm during this period.
  • A female participant is eligible to participate if she is not pregnant, not breastfeeding, and either not a woman of childbearing potential (WOCBP) OR if a WOCBP agrees to follow the study contraceptive guidance during the treatment period and for at least 120 days after the last dose of study treatment.

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 therapy, or has not recovered to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE)NCI CTCAE version 4 Grade 1 or better from any AEs that were due to cancer therapeutics administered more than 4 weeks earlier
  • Has not recovered from all radiation-related toxicities to Grade 1 or less, requires corticosteroids, and had radiation pneumonitis.
  • Has a history of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years.
  • Has known untreated central nervous system (ie, brain and/or spinal cord) metastases or known carcinomatous meningitis.
  • Has received any prior immunotherapy and was discontinued from that treatment due to a Grade 3 or higher residual immune-related AEs
  • Previously had a severe hypersensitivity reaction to treatment with a monoclonal antibody or has a known sensitivity to any component of pembrolizumab.
  • Has an active infection requiring therapy.
  • Has a history of interstitial lung disease.
  • Has a history of (noninfectious) pneumonitis that required steroids or current pneumonitis.
  • Has an active autoimmune disease that has required systemic treatment in the past 2 years (ie, with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs) except vitiligo or resolved childhood asthma/atopy.
  • Has clinically significant cardiac disease, including unstable angina, acute myocardial infarction within 6 months from Day 1 of study drug administration, or New York Heart Association Class III or IV congestive heart failure.
  • Known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies).
  • Known active hepatitis B or C.
  • Is taking chronic systemic steroids in doses >10 mg daily of prednisone or equivalent within 7 days prior to the first dose of trial treatment.
  • Has not fully recovered from any effects of major surgery without significant detectable infection. Surgeries that required general anesthesia must be completed at least 2 weeks before first study treatment administration. Surgery requiring regional/epidural anesthesia must be completed at least 72 hours before first study treatment administration and participants should be recovered.
  • Has received a live virus vaccine within 30 days of planned treatment start.
  • Is currently participating and receiving study therapy in a study of an investigational agent or has participated and received study therapy in a study of an investigational agent or has used an investigational device within 28 days of administration of MK-4830.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03564691


Contacts
Contact: Toll Free Number 1-888-577-8839 Trialsites@merck.com

Locations
United States, Michigan
Henry Ford Health System ( Site 0002) Recruiting
Detroit, Michigan, United States, 48202
Contact: Study Coordinator    313-916-7453      
United States, Texas
South Texas Accelerated Research Therapeutics, LLC (START) ( Site 0001) Recruiting
San Antonio, Texas, United States, 78229
Contact: Study Coordinator    210-593-5265      
Canada, Ontario
The Ottawa Hospital ( Site 0031) Recruiting
Ottawa, Ontario, Canada, K1H 8L6
Contact: Study Coordinator    613737770070185      
Princess Margaret Cancer Centre ( Site 0033) Recruiting
Toronto, Ontario, Canada, M5G 2M9
Contact: Study Coordinator    4169462911      
Israel
Rambam Medical Center ( Site 0042) Recruiting
Haifa, Israel, 3109601
Contact: Study Coordinator    +972535316961      
Sourasky Medical Center ( Site 0041) Recruiting
Tel Aviv, Israel, 6423906
Contact: Study Coordinator    +97236973082      
Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Study Director: Medical Director Merck Sharp & Dohme Corp.

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT03564691     History of Changes
Other Study ID Numbers: 4830-001
MK-4830-001 ( Other Identifier: Merck Protocol Number )
First Posted: June 21, 2018    Key Record Dates
Last Update Posted: September 10, 2018
Last Verified: September 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Merck Sharp & Dohme Corp.:
PD1
PD-1
PDL1
PD-L1

Additional relevant MeSH terms:
Pembrolizumab
Antineoplastic Agents