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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03473925




Registration number
NCT03473925
Ethics application status
Date submitted
8/03/2018
Date registered
22/03/2018

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)
Scientific title
A Phase II Study of Navarixin (MK-7123) in Combination With Pembrolizumab (MK-3475) in Participants With Selected Advanced/Metastatic Solid Tumors
Secondary ID [1] 0 0
MK-7123-034
Secondary ID [2] 0 0
7123-034
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Solid Tumors 0 0
Non-small Cell Lung Cancer 0 0
Castration Resistant Prostate Cancer 0 0
Microsatellite Stable Colorectal Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lung - Non small cell
Cancer 0 0 0 0
Bowel - Back passage (rectum) or large bowel (colon)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Navarixin
Treatment: Other - 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

Treatment: Other: Pembrolizumab
Intravenous infusion
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Objective Response Rate (ORR) Based on Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
Timepoint [1] 0 0
Up to approximately 2 years
Primary outcome [2] 0 0
Number of Participants With Dose-limiting Toxicities (DLTs) During Treatment Cycle 1
Timepoint [2] 0 0
Up to 21 days
Primary outcome [3] 0 0
Number of Participants Who Experience at Least One Adverse Event (AE)
Timepoint [3] 0 0
Up to approximately 27 months
Primary outcome [4] 0 0
Number of Participants Who Discontinue Study Treatment Due to an AE
Timepoint [4] 0 0
Up to approximately 2 years
Secondary outcome [1] 0 0
Objective Response Rate (ORR) Per Modified RECIST 1.1 for Immune-based Therapeutics (iRECIST)
Timepoint [1] 0 0
Up to approximately 2 years
Secondary outcome [2] 0 0
Progression-free Survival (PFS) Per RECIST 1.1
Timepoint [2] 0 0
Up to approximately 2 years
Secondary outcome [3] 0 0
PFS Per iRECIST
Timepoint [3] 0 0
Up to approximately 2 years
Secondary outcome [4] 0 0
Overall Survival (OS)
Timepoint [4] 0 0
Up to approximately 2 years
Secondary outcome [5] 0 0
Absolute Neutrophil Counts (ANC)
Timepoint [5] 0 0
Day 3: Predose
Secondary outcome [6] 0 0
Navarixin Area Under the Plasma Concentration-Time Curve (AUC) From Time 0 to Infinity (AUC0-inf)
Timepoint [6] 0 0
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)
Secondary outcome [7] 0 0
Navarixin Area Under the Plasma Concentration-Time Curve From Time 0 to Last (AUC0-last)
Timepoint [7] 0 0
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)
Secondary outcome [8] 0 0
Navarixin Maximum Plasma Concentration (Cmax)
Timepoint [8] 0 0
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)
Secondary outcome [9] 0 0
Navarixin Trough Plasma Concentration (Ctrough)
Timepoint [9] 0 0
Cycle 2 Day 21 (Up to approximately 43 days)

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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
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.).

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
10/04/2018
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
19/05/2021
Sample size
Target
Accrual to date
Final
107
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Blacktown Hospital Western Sydney Local Health District ( Site 0024) - Blacktown
Recruitment hospital [2] 0 0
Scientia Clinical Research ( Site 0021) - Randwick
Recruitment hospital [3] 0 0
Peter MacCallum Cancer Centre ( Site 0023) - Melbourne
Recruitment postcode(s) [1] 0 0
2148 - Blacktown
Recruitment postcode(s) [2] 0 0
2031 - Randwick
Recruitment postcode(s) [3] 0 0
3000 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Maryland
Country [4] 0 0
United States of America
State/province [4] 0 0
Michigan
Country [5] 0 0
United States of America
State/province [5] 0 0
North Carolina
Country [6] 0 0
Canada
State/province [6] 0 0
Ontario
Country [7] 0 0
Canada
State/province [7] 0 0
Quebec
Country [8] 0 0
Israel
State/province [8] 0 0
Tel Aviv
Country [9] 0 0
Korea, Republic of
State/province [9] 0 0
Gyeonggi-do
Country [10] 0 0
Korea, Republic of
State/province [10] 0 0
Seoul

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Merck Sharp & Dohme LLC
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Director
Address 0 0
Merck Sharp & Dohme LLC
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: http://engagezone.msd.com/ds_documentation.php


What supporting documents are/will be available?




Results publications and other study-related documents

TypeCitations or Other Details
Journal Armstrong AJ, Geva R, Chung HC, Lemech C, Miller W... [More Details]


Results are available at https://clinicaltrials.gov/study/NCT03473925