Clinical Trials /

Study of MK-7162 in Combination With Pembrolizumab (MK-3475) in Adult Participants With Advanced Solid Tumors (MK-7162-002)

NCT03364049

Description:

The purposes of this study are to: 1) determine the safety and tolerability of MK-7162 when administered in combination with pembrolizumab (MK-3475), 2) establish a preliminary recommended Phase 2 dose (RP2D) of MK-7162 when administered in combination with pembrolizumab, and 3) assess the pharmacokinetics and pharmacodynamics of MK-7162 when administered in combination with pembrolizumab and other therapies to adult participants with advanced solid tumors.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Study of MK-7162 in Combination With Pembrolizumab (MK-3475) in Adult Participants With Advanced Solid Tumors (MK-7162-002)
  • Official Title: Phase 1b Open-label Study of MK-7162 in Combination With Pembrolizumab (MK-3475) +/- Other Therapies in Participants With Advanced Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: 7162-002
  • SECONDARY ID: 2017-000418-49
  • SECONDARY ID: MK-7162-002
  • NCT ID: NCT03364049

Conditions

  • Solid Neoplasms

Interventions

DrugSynonymsArms
MK-7162MK-7162+Pembrolizumab
PembrolizumabMK-3475MK-7162+Pembrolizumab

Purpose

The purposes of this study are to: 1) determine the safety and tolerability of MK-7162 when administered in combination with pembrolizumab (MK-3475), 2) establish a preliminary recommended Phase 2 dose (RP2D) of MK-7162 when administered in combination with pembrolizumab, and 3) assess the pharmacokinetics and pharmacodynamics of MK-7162 when administered in combination with pembrolizumab and other therapies to adult participants with advanced solid tumors.

Trial Arms

NameTypeDescriptionInterventions
MK-7162+PembrolizumabExperimentalCycle 1: Participants receive MK-7162 (at a daily dose of between 25 mg and 400 mg) via oral tablets once daily (QD) throughout the 3-week cycle. Cycles 2 through 36: Participants receive MK-7162 (at a daily dose of between 25 mg and 400 mg) via oral tablets QD PLUS pembrolizumab 200 mg via intravenous (IV) infusion on Day 1 of each 3-week cycle (every 3 weeks [Q3W]).
  • MK-7162
  • Pembrolizumab

Eligibility Criteria

        Inclusion Criteria:

          -  Has a histologically- or cytologically-confirmed advanced/metastatic solid tumor by
             pathology report and have received, or been intolerant to, or been ineligible for all
             treatment known to confer clinical benefit. Participants with solid tumors of any type
             are eligible for enrollment.

          -  Has stage III or stage IV disease that is not surgically resectable.

          -  Has measureable disease by RECIST 1.1 criteria as assessed by the local site
             investigator/radiology.

          -  Has 1 or more discrete malignant lesions that are amenable to ≥2 separate biopsies
             guided by one of the following modalities: visual inspection, ultrasound guidance, or
             cross sectional image guidance (computed tomography/magnetic resonance imaging
             [CT/MRI]).

          -  Has an evaluable baseline tumor sample to submit for analysis.

          -  Has a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG)
             Performance Scale.

          -  Demonstrates adequate organ function.

          -  If male, must agree to use contraception and refrain from donating sperm during the
             treatment period and for ≥120 days after last dose of study treatment.

          -  If female, is not pregnant or breastfeeding, and agrees to use contraception during
             the treatment period and for ≥120 days after last dose of study treatment.

        Exclusion Criteria:

          -  Has a history of a second malignancy, unless potentially curative treatment has been
             completed with no evidence of malignancy for 2 years. (Note: The time requirement does
             not apply to participants who underwent successful definitive resection of basal cell
             carcinoma of the skin, superficial bladder cancer, in situ cervical cancer, or other
             in-situ cancers.)

          -  Has a known active central nervous system metastasis and/or carcinomatous meningitis.

          -  Has had a severe hypersensitivity reaction to treatment with a monoclonal
             antibody/components of the study treatment(s).

          -  Has an active autoimmune disease that has required systemic treatment in the past 2
             years except vitiligo or resolved childhood asthma/atopy.

          -  Has a history of vasculitis.

          -  Has an active infection requiring systemic therapy.

          -  Has symptomatic ascites or pleural effusion.

          -  Has interstitial lung disease that has required oral or intravenous glucocorticoids to
             assist with management.

          -  Has a history of (non-infectious) pneumonitis that required steroids or has current
             pneumonitis.

          -  Has undergone prior allogeneic hematopoietic stem cell transplantation within the last
             5 years. (Note: Participants who have had a stem cell transplant >5 years ago are
             eligible as long as there are no symptoms of graft-versus-host disease [GVHD].)

          -  Has a known history of human immunodeficiency virus (HIV) infection.

          -  Has known active Hepatitis B or known active Hepatitis C virus infection.

          -  Is pregnant or breastfeeding, or expecting to conceive or father children within the
             projected duration of the study.

          -  Has not fully recovered from any effects of major surgery without significant
             detectable infection.

          -  Has received prior systemic anti-cancer therapy including investigational agents or
             has used an investigational device within 28 days prior to the first dose of study
             treatment. (Notes: Participants must have recovered from all AEs due to previous
             therapies to ≤Grade 1 or baseline. Prior exposure to immunotherapeutics is allowed,
             including programmed cell death-1 (PD-1) and programmed cell death-ligand 1 (PD-L1)
             inhibitors, provided the participant did not experience ≥Grade 3 drug-related toxicity
             on monotherapy with a PD-1 or PD-L1 inhibitor.

          -  Has been previously treated with an Indoleamine-2,3-dioxygenase-1 (IDO1) inhibitor
             (e.g., epacadostat, BMS-986205)

          -  Has received prior radiotherapy within 2 weeks of start of study treatment.

          -  Is receiving an monoamine oxidase-inhibitors (MAOI) or any drug which has significant
             MAOI activity (e.g., meperidine, linezolid, methylene blue) within the 21 days before
             screening, or has a history of Serotonin Syndrome after receiving serotonergic drugs.

          -  Is expected to require any non-protocol antineoplastic therapy while on study.

          -  Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
             in excess of replacement doses (the equivalent of prednisone ≤10 mg/day is
             acceptable), or on any other form of immunosuppressive medication.

          -  Has received a live-virus vaccine within 30 days prior to first dose of study
             medication.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Dose-limiting Toxicities (DLTs) as Assessed Using Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 by the Investigator
Time Frame:Cycle 1 and Cycle 2 (Up to 6 weeks)
Safety Issue:
Description:The following events, if considered drug related by the Investigator, will be considered a DLT: Grade 4 nonhematologic toxicity; Grade 4 hematologic toxicity lasting ≥7 days, except thrombocytopenia; Grade 4 thrombocytopenia of any duration; Grade 3 thrombocytopenia associated with bleeding; Nonhematologic AEs ≥Grade 3 with exceptions; Grade 3 or Grade 4 non-hematologic laboratory values if requires medical intervention, leads to hospitalization, persists for >1 week, or results in a Drug-induced Liver Injury with exceptions; Grade 3 of 4 febrile neutropenia; Treatment-related toxicities that lead to discontinuation of study treatment during Cycles 1 or 2; Prolonged delay (>2 weeks) in initiating Cycles 2 or 3 due to treatment-related toxicity; Missing >25% of MK-7162 doses as a result of treatment-related AE during Cycles 1 or 2; Grade 5 toxicity. The number of participants who experience a DLT will be presented.

Secondary Outcome Measures

Measure:MK-7162 Area Under the Concentration-Time Curve (AUC) When Administered Alone and in Combination with Pembrolizumab
Time Frame:Cycle 1 Days 1 & 15: predose, 1, 2, 4 & 8 hours postdose; Cycle 2 Days 1 & 15: predose; Cycle 3 Day 1: predose, 1, 2, 4 & 8 hours postdose; Cycle 3 Day 15: predose; Cycles 4 through 36 Day 1: predose every 4 cycles (Up to approximately 25 months)
Safety Issue:
Description:Blood draws will be obtained at designated time points. The AUC of MK-7162 when administered alone and in combination with pembrolizumab will be presented.
Measure:MK-7162 Minimum Observed Concentration (Cmin) When Administered Alone and in Combination with Pembrolizumab
Time Frame:Cycle 1 Days 1 & 15: predose, 1, 2, 4 & 8 hours postdose; Cycle 2 Days 1 & 15: predose; Cycle 3 Day 1: predose, 1, 2, 4 & 8 hours postdose; Cycle 3 Day 15: predose; Cycles 4 through 36 Day 1: predose every 4 cycles (Up to approximately 25 months)
Safety Issue:
Description:Blood draws will be obtained at designated time points. The Cmin of MK-7162 when administered alone and in combination with pembrolizumab will be presented.
Measure:MK-7162 Maximum Observed Concentration (Cmax) When Administered Alone and in Combination with Pembrolizumab
Time Frame:Cycle 1 Days 1 & 15: predose, 1, 2, 4 & 8 hours postdose; Cycle 2 Days 1 & 15: predose; Cycle 3 Day 1: predose, 1, 2, 4 & 8 hours postdose; Cycle 3 Day 15: predose; Cycles 4 through 36 Day 1: predose every 4 cycles (Up to approximately 25 months)
Safety Issue:
Description:Blood draws will be obtained at designated time points. The Cmax of MK-7162 when administered alone and in combination with pembrolizumab will be presented.
Measure:Ratio of Kynurenine (KYN):Tryptophan (TRP) Biomarker Plasma Concentrations
Time Frame:Screening; Cycle 1 Days 1 & 15: predose, 1, 2, 4 & 8 hours postdose; Cycle 2 Day 1: predose; Cycle 3 Day 1: predose, 1, 2, 4 & 8 hours postdose; Cycle 3 Day 15: predose (Up to approximately 9 weeks)
Safety Issue:
Description:MK-7162 is a selective inhibitor of Indoleamine-2,3-dioxygenase-1 (IDO1) activity which, in turn, reduces the conversion of TRP to KYN. Venous blood samples will be collected after an overnight fast for measurement of plasma levels of KYN and TRP as a progressive disease (PD) biomarker of IDO1 inhibition. The ratio of KYN:TRP will be calculated at designated time points. A reduction (negative change from baseline) in KYN:TRP plasma concentration is indicative of a reduction in IDO1 activity.
Measure:Objective Response Rate (ORR) Based on Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by the Investigator
Time Frame:Up to approximately 25 months
Safety Issue:
Description:ORR is defined as the percentage of participants in the analysis population 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, taking as reference the baseline sum diameters) per RECIST 1.1 as assessed by the Investigator. The percentage of participants who experience a CR or PR based on RECIST 1.1 will be presented.
Measure:ORR Based on Immune-related RECIST (irRECIST) as Assessed by the Investigator
Time Frame:Up to approximately 25 months
Safety Issue:
Description:For participants with radiological PD by RECIST 1.1 as determined by the Investigator, will undergo confirmatory imaging which will classify participant disease as confirmed progressive disease [iCPD]), or as unconfirmed progressive disease [iUPD]), or as disease stability or response (stable disease [iSD]/partial response [iPR]/confirmed response [iCR]). iCPD definition: Target lesions, worsening is a further increase in the sum of diameters of ≥5 mm; Non-target lesions, worsening is any significant growth in lesions overall; New lesions, worsening is any of these: an increase in new lesion sum of diameters by ≥5 mm; Visible growth of new non-target lesions; Appearance of additional new lesions; or any new factor appears that would have triggered PD by RECIST 1.1. Responses are classified as iSD or iPR (depending on the sum of diameters of the target lesions), or iCR if all lesions resolve. The percentage of participants who experience iSD, iPR or iCR will be presented.

Details

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

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