Clinical Trials /

A Study of MK-0482 as Monotherapy and in Combination With Pembrolizumab (MK-3475) in Participants With Advanced Solid Tumors (MK-0482-001)

NCT03918278

Description:

This is a dose escalation study to determine the safety and pharmacokinetics of MK-0482 as monotherapy and in combination with pembrolizumab (MK-3475) in participants with advanced solid tumors for which there is no available therapy which may convey clinical benefit.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study of MK-0482 as Monotherapy and in Combination With Pembrolizumab (MK-3475) in Participants With Advanced Solid Tumors (MK-0482-001)
  • Official Title: A Phase 1b, Open-Label, Dose Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of MK-0482 as Monotherapy and in Combination With Pembrolizumab in Participants With Advanced/Metastatic Solid Tumors.

Clinical Trial IDs

  • ORG STUDY ID: 0482-001
  • SECONDARY ID: MK-0482-001
  • NCT ID: NCT03918278

Conditions

  • Neoplasms

Interventions

DrugSynonymsArms
MK-0482MK-0482 Monotherapy
pembrolizumabMK-3475, KEYTRUDA®MK-0482 + Pembrolizumab Combination Therapy

Purpose

This is a dose escalation study to determine the safety and pharmacokinetics of MK-0482 as monotherapy and in combination with pembrolizumab (MK-3475) in participants with advanced solid tumors for which there is no available therapy which may convey clinical benefit.

Trial Arms

NameTypeDescriptionInterventions
MK-0482 MonotherapyExperimentalParticipants receive escalating doses of MK-0482 via intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W) for up to 35 administrations (up to approximately 2 years).
  • MK-0482
MK-0482 + Pembrolizumab Combination TherapyExperimentalParticipants receive escalating doses of MK-0482 via IV infusion + pembrolizumab 200 mg via IV infusion on Day 1 of each 21-day cycle (Q3W) for up to 35 administrations (up to approximately 2 years).
  • MK-0482
  • pembrolizumab

Eligibility Criteria

        Inclusion Criteria:

          -  Has histologically-or cytologically-confirmed advanced/metastatic solid tumors by
             pathology report and have received, been intolerant to, or been ineligible for, all
             treatments known to confer clinical benefit

          -  Has measurable disease by Response Evaluation Criteria in Solid Tumors Version 1.1
             (RECIST 1.1) as assessed by the local site investigator/radiology

          -  Has provided an evaluable baseline tumor tissue sample

          -  Has ≥1 discrete malignant lesions that are amenable to biopsy

          -  Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1

          -  A female participant is eligible to participate if she is not pregnant or
             breastfeeding, and ≥1 of the following conditions applies: is not a woman of
             childbearing potential (WOCBP) OR is using a contraceptive method that is highly
             effective or is abstinent from heterosexual intercourse as their preferred and usual
             lifestyle during the intervention period and for ≥120 days after the last dose of
             study treatment

          -  Has a negative highly sensitive pregnancy test within 72 hours before the first dose
             of study treatment

          -  Human immunodeficiency virus (HIV) infected participants must have well controlled HIV
             on anti-retroviral therapy (ART)

        Exclusion Criteria:

          -  Has a history of a second malignancy, unless potentially curative treatment has been
             completed with no evidence of recurrence for ≥2 years

          -  Has a known additional malignancy that is progressing or has required active treatment
             within the past 2 years; with the exception of basal cell carcinoma of the skin,
             squamous cell carcinoma of the skin, or carcinoma in situ (eg, breast carcinoma,
             cervical cancer in situ) that have undergone potentially curative therapy

          -  Has known active central nervous system metastases and/or carcinomatous meningitis

          -  Has had a severe hypersensitivity reaction to treatment with a monoclonal antibody
             (mAb) and/or any component of pembrolizumab (MK-3475) or MK-0482

          -  Has received any prior immunotherapy and was discontinued from that treatment due to a
             Grade 3 or higher immune-related adverse event (irAE)

          -  Has an active infection requiring systemic therapy

          -  Has a history of interstitial lung disease

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

          -  Has an active autoimmune disease that has required systemic treatment in the past 2
             years

          -  HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric
             Castleman's Disease

          -  Has known Hepatitis B or C infection

          -  Has received prior systemic anticancer therapy, definitive radiotherapy, including
             investigational agents within 4 weeks (2 weeks for palliative radiation) prior to the
             first dose of study treatment

          -  Has not recovered from all radiation-related toxicities to Grade 1 or less

          -  Surgeries that required general anesthesia must be completed ≥2 weeks before first
             study treatment administration. Surgery requiring regional/epidural anesthesia must be
             completed ≥72 hours before first study treatment

          -  Has received a live vaccine within 30 days prior to the first dose of study treatment

          -  Is currently participating in or has participated in a study of an investigational
             agent or has used an investigational device within 28 days prior to the first dose of
             study treatment.

          -  Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
             or any other form of immunosuppressive therapy within 7 days prior the first dose of
             study treatment

          -  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

          -  Has had an allogeneic tissue/solid organ transplant in the last 5 years or has
             evidence of graft-versus-host disease
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of Participants Who Experience a Dose-Limiting Toxicity (DLT) Graded Using National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0
Time Frame:Cycle 1 (Up to 21 days)
Safety Issue:
Description:DLTs defined as any of the following assessed as treatment (Tx)-related by investigator: Grade (Gr)4 nonhematologic toxicity; Gr4 hematologic toxicity lasting ≥7 days, except thrombocytopenia; Gr4 thrombocytopenia of any duration; Gr3 thrombocytopenia associated with clinically-significant bleeding; nonhematologic adverse event (AE) ≥Gr3 in severity, with exceptions; Gr3/4 alanine transaminase (ALT), aspartate transaminase (AST), and/or bilirubin (bili) with exceptions; a protocol-defined elevation of ALT, AST, and bili; Gr3/4 nonhematologic laboratory abnormality if: clinically significant medical intervention is required, leads to hospitalization, persists for >1 week, or results in liver injury with exceptions; Gr3/4 febrile neutropenia; >2 week-delay in starting Cycle 2 due to Tx-related toxicity; Tx-related toxicity resulting in Tx discontinuation during Cycle 1; missing >25% of the MK-0482 and/or pembrolizumab doses during Cycle 1 resulting from Tx-related AE; or Gr5 toxicity.

Secondary Outcome Measures

Measure:Minimum Serum Concentration (Cmin) of MK-0482 When Administered as Monotherapy
Time Frame:At designated time points (Up to approximately 25 months)
Safety Issue:
Description:Blood samples will be obtained at designated time points for the assessment of MK-0482 Cmin (Cycle 1 Day 1: Predose and at end of administration [within 30 minutes after the end of infusion]; Cycle 1 Days 2, 4, 8 and 15: Once daily; Cycles 2, 4, 6, 8 and every 4 cycles thereafter: Predose and at end of administration [within 30 minutes after the end of infusion]; and at end of treatment/discontinuation [Up to approximately 25 months]). Each cycle is 21 days.
Measure:Minimum Serum Concentration (Cmin) of MK-0482 When Administered in Combination with Pembrolizumab
Time Frame:At designated time points (Up to approximately 25 months)
Safety Issue:
Description:Blood samples will be obtained at designated time points for the assessment of MK-0482 Cmin (Cycle 1 Day 1: Predose and at end of administration [within 30 minutes after the end of infusion]; Cycle 1 Days 2, 4, 8 and 15: Once daily; Cycles 2, 4, 6, 8 and every 4 cycles thereafter: Predose and at end of administration [within 30 minutes after the end of infusion]; and at end of treatment/discontinuation [Up to approximately 25 months]). Each cycle is 21 days.
Measure:Maximum Serum Concentration (Cmax) of MK-0482 When Administered as Monotherapy
Time Frame:At designated time points (Up to approximately 25 months)
Safety Issue:
Description:Blood samples will be obtained at designated time points for the assessment of MK-0482 Cmax (Cycle 1 Day 1: Predose and at end of administration [within 30 minutes after the end of infusion]; Cycle 1 Days 2, 4, 8 and 15: Once daily; Cycles 2, 4, 6, 8 and every 4 cycles thereafter: Predose and at end of administration [within 30 minutes after the end of infusion]; and at end of treatment/discontinuation [Up to approximately 25 months]). Each cycle is 21 days.
Measure:Maximum Serum Concentration (Cmax) of MK-0482 When Administered in Combination with Pembrolizumab
Time Frame:At designated time points (Up to approximately 25 months)
Safety Issue:
Description:Blood samples will be obtained at designated time points for the assessment of MK-0482 Cmax (Cycle 1 Day 1: Predose and at end of administration [within 30 minutes after the end of infusion]; Cycle 1 Days 2, 4, 8 and 15: Once daily; Cycles 2, 4, 6, 8 and every 4 cycles thereafter: Predose and at end of administration [within 30 minutes after the end of infusion]; and at end of treatment/discontinuation [Up to approximately 25 months]). Each cycle is 21 days.
Measure:Area Under the Concentration-Time Curve (AUC) of MK-0482 When Administered as Monotherapy
Time Frame:At designated time points (Up to approximately 25 months)
Safety Issue:
Description:Blood samples will be obtained at designated time points for the assessment of MK-0482 AUC (Cycle 1 Day 1: Predose and at end of administration [within 30 minutes after the end of infusion]; Cycle 1 Days 2, 4, 8 and 15: Once daily; Cycles 2, 4, 6, 8 and every 4 cycles thereafter: Predose and at end of administration [within 30 minutes after the end of infusion]; and at end of treatment/discontinuation [Up to approximately 25 months]). Each cycle is 21 days.
Measure:Area Under the Concentration-Time Curve (AUC) of MK-0482 When Administered in Combination with Pembrolizumab
Time Frame:At designated time points (Up to approximately 25 months)
Safety Issue:
Description:Blood samples will be obtained at designated time points for the assessment of MK-0482 AUC (Cycle 1 Day 1: Predose and at end of administration [within 30 minutes after the end of infusion]; Cycle 1 Days 2, 4, 8 and 15: Once daily; Cycles 2, 4, 6, 8 and every 4 cycles thereafter: Predose and at end of administration [within 30 minutes after the end of infusion]; and at end of treatment/discontinuation [Up to approximately 25 months]). Each cycle is 21 days.

Details

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

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