Clinical Trials /

Efficacy and Safety Study of Navarixin (MK-7123) in Combination With Pembrolizumab (MK-3475) in Adults With Selected Advanced/Metastatic Solid Tumors (MK-7123-034)

NCT03473925

Description:

The purpose of this study is to assess the efficacy and safety of navarixin (MK-7123) in combination with pembrolizumab (MK-3475) in adults with one of three types of solid tumors: Programmed Death-Ligand 1 (PD-L1) positive refractory non-small cell lung cancer (NSCLC), castration resistant prostate cancer (CRPC) or microsatellite stable (MSS) colorectal cancer (CRC).

Related Conditions:
  • Colorectal Carcinoma
  • Non-Small Cell Lung Carcinoma
  • Prostate Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Efficacy and Safety Study of Navarixin (MK-7123) in Combination With Pembrolizumab (MK-3475) in Adults With Selected Advanced/Metastatic Solid Tumors (MK-7123-034)
  • Official Title: A Phase II Study of Navarixin (MK-7123) in Combination With Pembrolizumab (MK-3475) in Participants With Selected Advanced/Metastatic Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: 7123-034
  • SECONDARY ID: MK-7123-034
  • NCT ID: NCT03473925

Conditions

  • Solid Tumors
  • Non-small Cell Lung Cancer
  • Castration Resistant Prostate Cancer
  • Microsatellite Stable Colorectal Cancer

Interventions

DrugSynonymsArms
NavarixinMK-7123, SCH 527123Navarixin Dose A + Pembrolizumab
PembrolizumabMK-3475Navarixin Dose A + Pembrolizumab

Purpose

The purpose of this study is to assess the efficacy and safety of navarixin (MK-7123) in combination with pembrolizumab (MK-3475) in adults with one of three types of solid tumors: Programmed Death-Ligand 1 (PD-L1) positive refractory non-small cell lung cancer (NSCLC), castration resistant prostate cancer (CRPC) or microsatellite stable (MSS) colorectal cancer (CRC).

Trial Arms

NameTypeDescriptionInterventions
Navarixin Dose A + PembrolizumabExperimentalParticipants receive navarixin Dose A via oral capsules once daily PLUS pembrolizumab 200 mg via intravenous infusion on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years).
  • Navarixin
Navarixin Dose B + PembrolizumabExperimentalParticipants receive navarixin Dose B via oral capsules once daily PLUS pembrolizumab 200 mg via intravenous infusion on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years).
  • Navarixin

Eligibility Criteria

        Inclusion Criteria:

        All Participants

          -  Has one of the following histologically- or cytologically-confirmed
             advanced/metastatic solid tumors: NSCLC, CRPC, or MSS CRC, by pathology report and has
             received, or been intolerant to, or has been ineligible for all treatment known to
             confer clinical benefit.

          -  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 supplied tumor tissue from either a newly obtained biopsy or an archival specimen
             for biomarker analysis.

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

          -  Male participants must agree to use contraception during the treatment period and for
             at least 120 days after the last dose of study treatment and refrain from donating
             sperm during this period.

          -  Female participants must agree to follow the contraceptive guidance during the
             treatment period and for at least 120 days after the last dose of study treatment.

          -  Demonstrates adequate organ function.

        Non-small Cell Lung Cancer (NSCLC) Participants

          -  Has histologically or cytologically confirmed diagnosis of Stage IV metastatic NSCLC.

          -  Has progressed on treatment with an anti-Programmed Death-Ligand 1 (PD-L1) monoclonal
             antibody (mAb) administered either as monotherapy, or in combination with other
             checkpoint inhibitors or other therapies. PD-L1 treatment progression is defined by
             meeting all of the following criteria: a) Has received ≥2 doses of an approved
             anti-PD-L1 mAb; b) Has demonstrated disease progression after anti-PD-L1 as defined by
             RECIST 1.1; c) Progressive disease has been documented within 12 weeks from the last
             dose of anti-PD-L1 mAb.

        Castration Resistant Prostate Cancer (CRPC) Participants

          -  Has histologically- or cytologically-confirmed adenocarcinoma of the prostate.
             Components of small cell prostate cancer are permitted.

          -  Has prostate cancer progression on the most recent treatment, as determined by the
             investigator, by means of one of the following: a) Prostate-Specific Antigen (PSA)
             progression using local laboratory values as defined by a minimum of 2 rising PSA
             levels with an interval of ≥1 week between each assessment where the PSA value at
             screening should be ≥2 ng/mL; b) Radiographic disease progression in soft tissue based
             on RECIST 1.1 criteria with or without PSA progression; c) Radiographic disease
             progression in bone defined as the appearance of 2 or more new bone lesions on bone
             scan with or without PSA progression.

          -  Has progressed on at least one second generation anti-androgen therapy (e.g.,
             enzalutamide, abiraterone).

          -  Has ongoing androgen deprivation with serum testosterone <50 ng/dL (<2.0 nM).

        Microsatellite Stable Colorectal Cancer (MSS-CRC) Participants

          -  Has a histologically proven locally advanced unresectable or metastatic (Stage IV)
             CRC.

          -  Has locally confirmed (MSS) CRC; participants with microsatellite instability-high
             (MSI-H) or microsatellite unstable CRC are not eligible.

          -  Has been previously treated with standard therapies, which must include
             fluoropyrimidine, oxaliplatin, and irinotecan.

        Exclusion Criteria:

          -  Has a known additional malignancy that is progressing or has required active treatment
             within the past 2 years. Note: Participants with basal cell carcinoma of the skin,
             squamous cell carcinoma of the skin, or carcinoma in situ (e.g. breast carcinoma,
             cervical cancer in situ) that have undergone potentially curative therapy are not
             excluded.

          -  Has known active central nervous system (CNS) metastases and/or carcinomatous
             meningitis. Participants with previously treated brain metastases may participate
             provided they are radiologically stable, i.e., without evidence of progression for at
             least 4 weeks by repeat imaging, clinically stable and without requirement of steroid
             treatment for at least 14 days prior to first dose of study treatment.

          -  Has had a severe hypersensitivity reaction to treatment with any mAb or 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. Participants who have
             previously been permanently discontinued from PD-(L)1 therapy due to immune related
             side effects are not eligible for this study.

          -  Has an active infection requiring systemic therapy.

          -  Has symptomatic ascites or pleural effusion.

          -  Has interstitial lung disease that 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 a known history of Hepatitis B or known active Hepatitis C virus infection.

          -  Has a history or current evidence of a gastrointestinal condition (e.g. inflammatory
             bowel disease, Crohn's disease, ulcerative colitis) or impaired liver function or
             diseases that in the opinion of the Investigator may significantly alter the
             absorption or metabolism of oral medications; any condition, therapy, or laboratory
             abnormality that might confound the results of the study, interfere with the
             participant's participation for the full duration of the study, make administration of
             the study drugs hazardous, or make it difficult to monitor AEs such that it is not in
             the best interest of the participant to participate, in the opinion of the treating
             Investigator.

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

          -  Has undergone major surgery and has not recovered adequately from any toxicity and/or
             complications from the intervention prior to starting study treatment.

          -  Has CRPC or MSS CRC and has received prior therapy with an anti-PD-1, anti-PD-L1, or
             anti-PD-L2 agent.

          -  Has been treated with an agent directed to another stimulatory or co-inhibitory Tcell
             receptor (e.g. cytotoxic T-lymphocyte protein 4 [CTLA-4], tumor necrosis factor
             receptor superfamily, member 4 [OX 40], tumor necrosis factor receptor superfamily
             member 9 [CD137]).

          -  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.

          -  Has received prior radiotherapy (not to target lesions) within 2 weeks of start of
             study treatment.

          -  Is expected to require any other form of antineoplastic therapy while on study.

          -  Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
             in excess of replacement doses (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
             treatment.

          -  Has been previously treated with a chemokine receptor 2 (CXCR2) inhibitor (e.g.
             AZD5069, reparixin, danirixin, LY3041658 Ab, HuMax-IL8, etc.).
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective Response Rate (ORR) based on Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
Time Frame:Up to approximately 2 years
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) per RECIST 1.1. ORR will be assessed by the investigator following administration of navarixin in combination with pembrolizumab. The percentage of participants who experience a CR or PR per RECIST 1.1 will be presented.

Secondary Outcome Measures

Measure:Objective Response Rate (ORR) Per Modified RECIST 1.1 for Immune-based Therapeutics (iRECIST)
Time Frame:Up to approximately 2 years
Safety Issue:
Description:An objective response is defined as an immune-based Complete Response (iCR: Disappearance of all target lesions) or immune-based Partial Response (iPR: At least a 30% decrease in the sum of diameters of target lesions). ORR will be assessed by the investigator based on iRECIST following administration of navarixin in combination with pembrolizumab. The percentage of participants who experience an iCR or iPR will be presented.
Measure:Progression-free Survival (PFS) Per RECIST 1.1
Time Frame:Up to approximately 2 years
Safety Issue:
Description:PFS is defined as the time from the first dose of study treatment to the first confirmed documented disease progression, or death due to any cause, whichever occurs first. Per RECIST 1.1, progressive disease is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. Note: The appearance of one or more new lesions is also considered progression. PFS per RECIST 1.1 will be assessed by the investigator.
Measure:PFS Per iRECIST
Time Frame:Up to approximately 2 years
Safety Issue:
Description:PFS is defined as the time from the first dose of study treatment to the first documented disease progression or death due to any cause, whichever occurs first. Per iRECIST, progressive disease (PD) is defined as ≥20% increase in the sum of diameters of target lesions. In addition after iRECIST-unconfirmed progressive disease (iUPD); target lesion increase of >5 mm compared to any prior iUPD time point, for non-target lesions, any significant growth in lesions overall compared to a prior iUPD time point that does not meet unequivocal standard RECIST 1.1 and a further increase in the sum of diameters by >5 mm from a prior iUPD time point, visible growth of new non-target lesions and the appearance of additional new lesions and any new factor that would trigger PD by RECIST 1.1. Per iRECIST, disease progression is to be confirmed by a consecutive assessment at least 4-8 weeks after first documentation and will be assessed by the investigator.
Measure:Overall Survival (OS)
Time Frame:Up to approximately 2 years
Safety Issue:
Description:OS is defined as the time from the first dose of study treatment to death due to any cause.
Measure:Absolute Neutrophil Counts (ANC)-related AEs
Time Frame:Up to approximately 2 years
Safety Issue:
Description:Peripheral blood neutrophil counts are to be performed at specified time points (Cycle 1 Day 1: Predose, 6-12 hours postdose; Cycle 1 Days 3 & 8: 6-12 hours postdose; Cycle 2 Day 1: Predose, 6-12 hours postdose; Cycles 3-35 Day 1: Predose) for the determination of ANC-related AEs. The number of participants who experience an ANC-related AE will be presented.
Measure:Navarixin Area Under the Plasma Concentration-Time Curve (AUC)
Time Frame:At designated time points (Up to approximately 23 days)
Safety Issue:
Description:Plasma samples are to be collected at specified time points (Cycle 1 Day 1: Predose & 1, 2, 4, 6 & 8-12 hours postdose; Cycle 1 Days 3 & 8: Predose & 6-12 hours postdose; Cycle 2 Day 1: Predose & 1, 2, 4, 6 & 8-12 hours postdose) for the determination of navarixin AUC. The navarixin plasma AUC will be presented.
Measure:Navarixin Maximum Plasma Concentration (Cmax)
Time Frame:At designated time points (Up to approximately 23 days)
Safety Issue:
Description:Plasma samples are to be collected at specified time points (Cycle 1 Day 1: Predose & 1, 2, 4, 6 & 8-12 hours postdose; Cycle 1 Days 3 & 8: Predose & 6-12 hours postdose; Cycle 2 Day 1: Predose & 1, 2, 4, 6 & 8-12 hours postdose) for the determination of navarixin Cmax. The navarixin plasma Cmax will be presented.
Measure:Navarixin Trough Plasma Concentration (Ctrough)
Time Frame:At designated time points (Up to approximately 2 years)
Safety Issue:
Description:Plasma samples are to be collected at specified time points (Cycles 1, 2, 4, 6 & 8 & every 4 cycles thereafter: Predose) for the determination of navarixin Ctrough. The navarixin plasma Ctrough will be presented.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Merck Sharp & Dohme Corp.

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