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 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 7123-034MK-7123-034
• Study Type: interventional
• Target: 107
• Locations: 5 countries
• Sites: 14

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).

Conditions

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

Outcome Measures

Primary Outcomes (4)

• Objective Response Rate (ORR) Based on Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)

  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.

  Up to approximately 2 years

• Number of Participants With Dose-limiting Toxicities (DLTs) During Treatment Cycle 1

  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

  Up to 21 days

• Number of Participants Who Experience at Least One Adverse Event (AE)

  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.

  Up to approximately 27 months

• Number of Participants Who Discontinue Study Treatment Due to an AE

  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.

  Up to approximately 2 years

Secondary Outcomes (9)

• Objective Response Rate (ORR) Per Modified RECIST 1.1 for Immune-based Therapeutics (iRECIST)

  Up to approximately 2 years

• Progression-free Survival (PFS) Per RECIST 1.1

  Up to approximately 2 years

• PFS Per iRECIST

  Up to approximately 2 years

• Overall Survival (OS)

  Up to approximately 2 years

• Absolute Neutrophil Counts (ANC)

  Day 3: Predose

Study Arms (2)

Navarixin 30 mg + Pembrolizumab 200 mg

EXPERIMENTAL

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

Drug: Navarixin; Biological: Pembrolizumab

Navarixin 100 mg + Pembrolizumab 200 mg

EXPERIMENTAL

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).

Drug: Navarixin; Biological: Pembrolizumab

Interventions

Navarixin DRUG

Oral capsules

Also known as: MK-7123, SCH 527123

Navarixin 100 mg + Pembrolizumab 200 mg; Navarixin 30 mg + Pembrolizumab 200 mg

Pembrolizumab BIOLOGICAL

Intravenous infusion

Also known as: MK-3475

Navarixin 100 mg + Pembrolizumab 200 mg; Navarixin 30 mg + Pembrolizumab 200 mg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (14)

Honor Health ( Site 0005)

Scottsdale, Arizona, 85258, United States

Location

Florida Cancer Specialists ( Site 0003)

Sarasota, Florida, 34232, United States

Location

University of Maryland ( Site 0008)

Baltimore, Maryland, 21201, United States

Location

Henry Ford Health System ( Site 0006)

Detroit, Michigan, 48202, United States

Location

Duke University Medical Center ( Site 0004)

Durham, North Carolina, 27710, United States

Location

Blacktown Hospital Western Sydney Local Health District ( Site 0024)

Blacktown, New South Wales, 2148, Australia

Location

Scientia Clinical Research ( Site 0021)

Randwick, New South Wales, 2031, Australia

Location

Peter MacCallum Cancer Centre ( Site 0023)

Melbourne, Victoria, 3000, Australia

Location

Princess Margaret Cancer Centre ( Site 0031)

Toronto, Ontario, M5G 2M9, Canada

Location

Jewish General Hospital ( Site 0032)

Montreal, Quebec, H3T 1E2, Canada

Location

Sourasky Medical Center ( Site 0012)

Tel Aviv, 6423906, Israel

Location

Seoul National University Bundang Hospital ( Site 0043)

Seongnam-si, Gyeonggi-do, 13620, South Korea

Location

Seoul National University Hospital ( Site 0042)

Seoul, 03080, South Korea

Location

Severance Hospital Yonsei University Health System ( Site 0041)

Seoul, 03722, South Korea

Location

Related Publications (1)

• Armstrong AJ, Geva R, Chung HC, Lemech C, Miller WH Jr, Hansen AR, Lee JS, Tsai F, Solomon BJ, Kim TM, Rolfo C, Giranda V, Ren Y, Liu F, Kandala B, Freshwater T, Wang JS. CXCR2 antagonist navarixin in combination with pembrolizumab in select advanced solid tumors: a phase 2 randomized trial. Invest New Drugs. 2024 Feb;42(1):145-159. doi: 10.1007/s10637-023-01410-2. Epub 2024 Feb 7.

  PMID: 38324085 RESULT

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

navarixin; 2-hydroxy-N,N-dimethyl-3-(2-((1-(5-methylfuran-2-yl)propyl)amino)-3,4-dioxocyclobut-1-enylamino)benzamide; pembrolizumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme LLC

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 8, 2018
• First Posted: March 22, 2018
• Study Start: April 10, 2018
• Primary Completion: May 19, 2021
• Study Completion: May 19, 2021
• Last Updated: August 28, 2024
• Results First Posted: June 29, 2022

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will share

Locations

US (5); KR (3); IL (1); CA (2); AU (3)