Clinical Trials /

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

NCT03564691

Description:

This study will determine the safety and tolerability and establish a preliminary recommended Phase 2 dose of MK-4830 administered as monotherapy and in combination with pembrolizumab (MK-3475) in participants with advanced solid tumors; determine the safety and tolerability for the combination of MK-4830 with pembrolizumab + carboplatin/pemetrexed in participants with non-small-cell lung carcinoma (NSCLC), and MK-4830 in combination with pembrolizumab + lenvatinib in renal cell cancer; and to evaluate objective response rate (ORR) in participants with advanced solid tumors treated with MK-4830 in combination with pembrolizumab.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: 4830-001
  • SECONDARY ID: MK-4830-001
  • NCT ID: NCT03564691

Conditions

  • Neoplasms

Interventions

DrugSynonymsArms
MK-4830Part A: MK-4830 Monotherapy
PembrolizumabMK-3475Part C: MK-4830 and Pembrolizumab

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Part A: MK-4830 MonotherapyExperimentalMK-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.
  • MK-4830
Part B: MK-4830 MonotherapyExperimentalMK-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.
  • MK-4830
Part C: MK-4830 and PembrolizumabExperimentalCombination 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.
  • MK-4830
  • Pembrolizumab

Eligibility 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Dose-Limiting Toxicities (DLTs)
Time Frame:Cycle 1 (Up to 21 days)
Safety Issue:
Description: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

Secondary Outcome Measures

Measure: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)
Safety Issue:
Description:Pharmacokinetic (PK) parameter: area under the drug concentration/time curve
Measure: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)
Safety Issue:
Description:PK parameter: minimum drug concentration
Measure: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)
Safety Issue:
Description:PK parameter: maximum drug concentration

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Merck Sharp & Dohme Corp.

Trial Keywords

  • PD1
  • PD-1
  • PDL1
  • PD-L1

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