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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/ct2/show/NCT03473925
Registration number
NCT03473925
Ethics application status
Date submitted
8/03/2018
Date registered
22/03/2018
Date last updated
29/06/2022
Titles & IDs
Public 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)
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Scientific title
A Phase II Study of Navarixin (MK-7123) in Combination With Pembrolizumab (MK-3475) in Participants With Selected Advanced/Metastatic Solid Tumors
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Secondary ID [1]
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MK-7123-034
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Secondary ID [2]
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7123-034
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Universal Trial Number (UTN)
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Trial acronym
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Solid Tumors
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Non-small Cell Lung Cancer
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Castration Resistant Prostate Cancer
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Microsatellite Stable Colorectal Cancer
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Condition category
Condition code
Cancer
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Lung - Non small cell
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Cancer
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Bowel - Back passage (rectum) or large bowel (colon)
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Treatment: Drugs - Navarixin
Other interventions - Pembrolizumab
Experimental: Navarixin 30 mg + Pembrolizumab 200 mg - Participants received 30 mg navarixin via oral capsules once daily, plus 200 mg pembrolizumab via IV infusion on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years
Experimental: Navarixin 100 mg + Pembrolizumab 200 mg - Participants received 100 mg navarixin via oral capsules once daily, plus 200 mg pembrolizumab via IV infusion on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years).
Treatment: Drugs: Navarixin
Oral capsules
Other interventions: Pembrolizumab
Intravenous infusion
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Intervention code [1]
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Treatment: Drugs
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Intervention code [2]
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Other interventions
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Objective Response Rate (ORR) Based on Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
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Assessment method [1]
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ORR is defined as the percentage of participants 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 was estimated using an exact method based on the binomial distribution, and the 95% confidence interval was estimated by the method of Clopper-Pearson.
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Timepoint [1]
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Up to approximately 2 years
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Primary outcome [2]
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Number of Participants With Dose-limiting Toxicities (DLTs) During Treatment Cycle 1
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Assessment method [2]
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The following toxicities are considered a DLT, 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
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Timepoint [2]
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Up to 21 days
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Primary outcome [3]
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Number of Participants Who Experience at Least One Adverse Event (AE)
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Assessment method [3]
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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.
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Timepoint [3]
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Up to approximately 27 months
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Primary outcome [4]
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Number of Participants Who Discontinue Study Treatment Due to an AE
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Assessment method [4]
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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.
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Timepoint [4]
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Up to approximately 2 years
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Secondary outcome [1]
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Objective Response Rate (ORR) Per Modified RECIST 1.1 for Immune-based Therapeutics (iRECIST)
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Assessment method [1]
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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 with progressive disease per RECIST 1.1 who experience an iCR or iPR are presented.
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Timepoint [1]
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Up to approximately 2 years
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Secondary outcome [2]
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Progression-free Survival (PFS) Per RECIST 1.1
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Assessment method [2]
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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. Median PFS per RECIST 1.1 was assessed by the investigator from product-limit (Kaplan-Meier) method for censored data in participants with microsatellite stable colorectal cancer (CRC); with castration-resistant prostate cancer (CRPC), and with programmed cell death ligand 1 (PD-[L]1) refractory non-small cell lung cancer (NSCLC).
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Timepoint [2]
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Up to approximately 2 years
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Secondary outcome [3]
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PFS Per iRECIST
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Assessment method [3]
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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. 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. Median PFS per iRECIST was assessed by the investigator from product-limit (Kaplan-Meier) method for censored data in participants with microsatellite stable colorectal cancer (CRC); with castration-resistant prostate cancer (CRPC), and with programmed cell death ligand 1 (PD-[L]1) refractory non-small cell lung cancer (NSCLC).
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Timepoint [3]
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Up to approximately 2 years
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Secondary outcome [4]
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Overall Survival (OS)
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Assessment method [4]
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OS is defined as the time from the first dose of study treatment to death due to any cause. Median OS was assessed from product-limit (Kaplan-Meier) method for censored data in participants with microsatellite stable colorectal cancer (CRC); with castration-resistant prostate cancer (CRPC), and with programmed cell death ligand 1 (PD-[L]1) refractory non-small cell lung cancer (NSCLC).
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Timepoint [4]
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Up to approximately 2 years
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Secondary outcome [5]
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Absolute Neutrophil Counts (ANC)
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Assessment method [5]
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Peripheral blood neutrophil counts were performed at Cycle 1 Day 3: Predose, to determine the concentration of ANC.
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Timepoint [5]
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Day 3: Predose
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Secondary outcome [6]
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Navarixin Area Under the Plasma Concentration-Time Curve (AUC) From Time 0 to Infinity (AUC0-inf)
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Assessment method [6]
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Plasma samples from participants with selected advanced/metastatic solid tumors were collected to determine the navarixin plasma AUC0-inf
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Timepoint [6]
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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 (Up to approximately 23 days)
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Secondary outcome [7]
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Navarixin Area Under the Plasma Concentration-Time Curve From Time 0 to Last (AUC0-last)
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Assessment method [7]
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Plasma samples from participants with selected advanced/metastatic solid tumors were collected to determine the navarixin plasma AUC0-last.
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Timepoint [7]
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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(Up to approximately 23 days)
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Secondary outcome [8]
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Navarixin Maximum Plasma Concentration (Cmax)
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Assessment method [8]
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Plasma samples from participants with selected advanced/metastatic solid tumors were collected to determine the navarixin plasma Cmax.
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Timepoint [8]
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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 (Up to approximately 23 days)
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Secondary outcome [9]
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Navarixin Trough Plasma Concentration (Ctrough)
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Assessment method [9]
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Plasma samples from participants with selected advanced/metastatic solid tumors were collected at steady state on Cycle 2 Day 21 to determine navarixin Ctrough. The Arithmetic Mean and CV% are presented.
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Timepoint [9]
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Cycle 2 Day 21 (Up to approximately 43 days)
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Eligibility
Key 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 measurable 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.
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Minimum age
18
Years
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Maximum age
No limit
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Sex
Both males and females
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Can healthy volunteers participate?
No
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Key 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.).
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Randomised controlled trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Open (masking not used)
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Who is / are masked / blinded?
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Intervention assignment
Parallel
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Other design features
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Phase
Phase 2
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Completed
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
10/04/2018
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
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Actual
19/05/2021
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Sample size
Target
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Accrual to date
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Final
107
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Recruitment in Australia
Recruitment state(s)
NSW,VIC
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Recruitment hospital [1]
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Blacktown Hospital Western Sydney Local Health District ( Site 0024) - Blacktown
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Recruitment hospital [2]
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Scientia Clinical Research ( Site 0021) - Randwick
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Recruitment hospital [3]
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Peter MacCallum Cancer Centre ( Site 0023) - Melbourne
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Recruitment postcode(s) [1]
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2148 - Blacktown
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Recruitment postcode(s) [2]
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2031 - Randwick
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Recruitment postcode(s) [3]
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3000 - Melbourne
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Recruitment outside Australia
Country [1]
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United States of America
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State/province [1]
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Arizona
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Country [2]
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United States of America
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State/province [2]
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Florida
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Country [3]
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United States of America
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State/province [3]
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Maryland
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Country [4]
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United States of America
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State/province [4]
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Michigan
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Country [5]
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United States of America
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State/province [5]
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North Carolina
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Country [6]
0
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Canada
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State/province [6]
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Ontario
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Country [7]
0
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Canada
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State/province [7]
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Quebec
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Country [8]
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Israel
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State/province [8]
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Tel Aviv
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Country [9]
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Korea, Republic of
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State/province [9]
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Gyeonggi-do
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Country [10]
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Korea, Republic of
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State/province [10]
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Seoul
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Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
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Name
Merck Sharp & Dohme LLC
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Address
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Country
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Ethics approval
Ethics application status
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Summary
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).
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Trial website
https://clinicaltrials.gov/ct2/show/NCT03473925
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Trial related presentations / publications
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Public notes
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Contacts
Principal investigator
Name
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Medical Director
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Address
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Merck Sharp & Dohme LLC
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Country
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Phone
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Fax
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Email
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Contact person for public queries
Name
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Address
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Phone
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Fax
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Email
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Contact person for scientific queries
Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/ct2/show/NCT03473925
Download to PDF