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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)

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ClinicalTrials.gov Identifier: NCT03473925
Recruitment Status : Recruiting
First Posted : March 22, 2018
Last Update Posted : June 25, 2018
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Brief Summary:
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).

Condition or disease Intervention/treatment Phase
Solid Tumors Non-small Cell Lung Cancer Castration Resistant Prostate Cancer Microsatellite Stable Colorectal Cancer Drug: Navarixin Biological: Pembrolizumab Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 120 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Study of Navarixin (MK-7123) in Combination With Pembrolizumab (MK-3475) in Participants With Selected Advanced/Metastatic Solid Tumors
Actual Study Start Date : April 10, 2018
Estimated Primary Completion Date : August 9, 2019
Estimated Study Completion Date : August 9, 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Navarixin Dose A + Pembrolizumab
Participants 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).
Drug: Navarixin
Oral capsules
Other Names:
  • MK-7123
  • SCH 527123

Biological: Pembrolizumab
Intravenous infusion
Other Name: MK-3475

Experimental: Navarixin Dose B + Pembrolizumab
Participants 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).
Drug: Navarixin
Oral capsules
Other Names:
  • MK-7123
  • SCH 527123

Biological: Pembrolizumab
Intravenous infusion
Other Name: MK-3475




Primary Outcome Measures :
  1. 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 ]
    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.

  2. Dose-limiting Toxicities (DLTs) During Cycle 1 [ Time Frame: Up to 21 days ]

    The following toxicities will be considered a DLT, if assessed as related to study treatment:

    • Grade 4 non-hematologic toxicity
    • Grade 4 anemia
    • Grade 3 anemia lasting >7 days or requiring transfusion
    • Grade 4 hematologic toxicity lasting ≥7 days, except thrombocytopenia; a) Grade 4 thrombocytopenia of any duration; b) Grade 3 thrombocytopenia associated with bleeding
    • Grade 3 non-hematologic toxicity lasting >3 days
    • Any Grade 3 or Grade 4 non-hematologic laboratory value if: medical intervention is required or the abnormality leads to hospitalization or persists for >72 hours
    • Liver test abnormalities: Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >3X Upper Limit of Normal (ULN) with total bilirubin (TBL) >2X ULN with no elevation in alkaline phosphatase (AP <2X ULN)
    • Grade 3 or Grade 4 febrile neutropenia
    • Inability to administer ≥75% of the planned navarixin dose due to drug-related tolerability
    • Delay in Cycle 2 start by >2 weeks due to toxicity

  3. Adverse Events (AEs) [ Time Frame: Up to approximately 27 months ]
    An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study treatment. The number of participants who experience at least one AE will be presented.

  4. Study Treatment Discontinuations Due to an AE [ Time Frame: Up to approximately 2 years ]
    The number of participants who discontinue study treatment due to an AE will be presented.


Secondary Outcome Measures :
  1. Objective Response Rate (ORR) Per Modified RECIST 1.1 for Immune-based Therapeutics (iRECIST) [ Time Frame: Up to approximately 2 years ]
    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.

  2. Progression-free Survival (PFS) Per RECIST 1.1 [ Time Frame: Up to approximately 2 years ]
    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.

  3. PFS Per iRECIST [ Time Frame: Up to approximately 2 years ]
    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.

  4. Overall Survival (OS) [ Time Frame: Up to approximately 2 years ]
    OS is defined as the time from the first dose of study treatment to death due to any cause.

  5. Absolute Neutrophil Counts (ANC)-related AEs [ Time Frame: Up to approximately 2 years ]
    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.

  6. Navarixin Area Under the Plasma Concentration-Time Curve (AUC) [ Time Frame: At designated time points (Up to approximately 23 days) ]
    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.

  7. Navarixin Maximum Plasma Concentration (Cmax) [ Time Frame: At designated time points (Up to approximately 23 days) ]
    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.

  8. Navarixin Trough Plasma Concentration (Ctrough) [ Time Frame: At designated time points (Up to approximately 2 years) ]
    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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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

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): NCT03473925


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

Locations
United States, Florida
Florida Cancer Specialists ( Site 0003) Recruiting
Sarasota, Florida, United States, 34232
Contact: Study Coordinator    941-377-9993      
United States, Michigan
Henry Ford Health System ( Site 0006) Recruiting
Detroit, Michigan, United States, 48202
Contact: Study Coordinator    313-916-1784      
Australia, New South Wales
Scientia Clinical Research ( Site 0021) Recruiting
Sydney, New South Wales, Australia, 2031
Contact: Study Coordinator    +61293825807      
Australia, Victoria
Peter MacCallum Cancer Centre ( Site 0023) Recruiting
Melbourne, Victoria, Australia, 3000
Contact: Study Coordinator    +61385595000      
Canada, Ontario
Princess Margaret Cancer Centre ( Site 0031) Recruiting
Toronto, Ontario, Canada, M5G 2M9
Contact: Study Coordinator    41694645015634      
Canada, Quebec
Jewish General Hospital ( Site 0032) Recruiting
Montreal, Quebec, Canada, H3T 1E2
Contact: Study Coordinator    5143408222      
Israel
Sourasky Medical Center ( Site 0012) 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: NCT03473925     History of Changes
Other Study ID Numbers: 7123-034
MK-7123-034 ( Other Identifier: Merck Protocol Number )
First Posted: March 22, 2018    Key Record Dates
Last Update Posted: June 25, 2018
Last Verified: June 2018

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

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Colorectal Neoplasms
Prostatic Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Genital Neoplasms, Male
Urogenital Neoplasms
Genital Diseases, Male
Prostatic Diseases
Pembrolizumab
Antineoplastic Agents