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NCT03473925

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)

Completed Phase 2 Results posted Last updated 28 August 2024
What this trial tests

Phase 2 trial testing Navarixin in Solid Tumors in 107 participants. Completed in 19 May 2021.

Timeline
10 April 2018
Primary endpoint
19 May 2021
19 May 2021

Quick facts

Lead sponsorMerck Sharp & Dohme LLC
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingnone
Primary purposetreatment
Enrollment107
Start date10 April 2018
Primary completion19 May 2021
Estimated completion19 May 2021
Sites14 locations across Israel, South Korea, Canada, Australia, United States

Drugs / interventions tested

Conditions studied

Sponsor

Merck Sharp & Dohme LLC — full company profile →

Who can join

18 and older, any sex, with Solid Tumors or Non-small Cell Lung Cancer. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Objective Response Rate (ORR) Based on Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Primary · Up to approximately 2 years

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.

GroupValue95% CI
Navarixin 30 mg + Pembrolizumab 200 mg3.90.5 – 13.5
Navarixin 100 mg + Pembrolizumab 200 mg1.90.0 – 9.9
Number of Participants With Dose-limiting Toxicities (DLTs) During Treatment Cycle 1 Primary · Up to 21 days

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 abnormal

GroupValue95% CI
Navarixin 30 mg + Pembrolizumab 200 mg2
Navarixin 100 mg + Pembrolizumab 200 mg3
Number of Participants Who Experience at Least One Adverse Event (AE) Primary · 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.

GroupValue95% CI
Navarixin 30 mg + Pembrolizumab 200 mg50
Navarixin 100 mg + Pembrolizumab 200 mg54
Number of Participants Who Discontinue Study Treatment Due to an AE Primary · Up to approximately 2 years

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.

GroupValue95% CI
Navarixin 30 mg + Pembrolizumab 200 mg4
Navarixin 100 mg + Pembrolizumab 200 mg6
Objective Response Rate (ORR) Per Modified RECIST 1.1 for Immune-based Therapeutics (iRECIST) Secondary · 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 with progressive disease per RECIST 1.1 who experience an iCR or iPR are presented.

iComplete Response (iCR)
GroupValue95% CI
Navarixin 30 mg + Pembrolizumab 200 mg0.00.0 – 8.2
Navarixin 100 mg + Pembrolizumab 200 mg0.00.0 – 8.6
iPartial Response (iPR)
GroupValue95% CI
Navarixin 30 mg + Pembrolizumab 200 mg0.00.0 – 8.2
Navarixin 100 mg + Pembrolizumab 200 mg0.00.0 – 8.6
Progression-free Survival (PFS) Per RECIST 1.1 Secondary · 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. Median PFS per RECIST 1.1 was assessed by the investigator from product-limit (Kaplan-Meier) method for censored data in participants w

CRC
GroupValue95% CI
Navarixin 30 mg + Pembrolizumab 200 mg1.81.0 – 2.0
Navarixin 100 mg + Pembrolizumab 200 mg1.91.6 – 2.0
CRPC
GroupValue95% CI
Navarixin 30 mg + Pembrolizumab 200 mg2.11.9 – 4.1
Navarixin 100 mg + Pembrolizumab 200 mg2.11.9 – 4.5
NSCLC
GroupValue95% CI
Navarixin 30 mg + Pembrolizumab 200 mg2.41.6 – 10.2
Navarixin 100 mg + Pembrolizumab 200 mg2.11.9 – 2.4
PFS Per iRECIST Secondary · 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. 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
GroupValue95% CI
Navarixin 30 mg + Pembrolizumab 200 mg4.12.1 – 7.1
Navarixin 100 mg + Pembrolizumab 200 mg6.23.3 – 14.4
CRPC
GroupValue95% CI
Navarixin 30 mg + Pembrolizumab 200 mg7.95.0 – 8.6
Navarixin 100 mg + Pembrolizumab 200 mg5.23.0 – 11.5
NSCLC
GroupValue95% CI
Navarixin 30 mg + Pembrolizumab 200 mg11.93.2 – 17.5
Navarixin 100 mg + Pembrolizumab 200 mg7.02.4 – 14.4
Overall Survival (OS) Secondary · Up to approximately 2 years

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).

CRC
GroupValue95% CI
Navarixin 30 mg + Pembrolizumab 200 mg6.53.0 – 9.7
Navarixin 100 mg + Pembrolizumab 200 mg8.05.7 – 14.4
CRPC
GroupValue95% CI
Navarixin 30 mg + Pembrolizumab 200 mg10.87.9 – 13.4
Navarixin 100 mg + Pembrolizumab 200 mg11.23.7 – 23.0
MSCLC
GroupValue95% CI
Navarixin 30 mg + Pembrolizumab 200 mg13.03.2 – 18.0
Navarixin 100 mg + Pembrolizumab 200 mg12.02.4 – 19.9
Absolute Neutrophil Counts (ANC) Secondary · Day 3: Predose

Peripheral blood neutrophil counts were performed at Cycle 1 Day 3: Predose, to determine the concentration of ANC.

GroupValue95% CI
Navarixin 30 mg + Pembrolizumab 200 mg3.63.03 – 4.12
Navarixin 100 mg + Pembrolizumab 200 mg3.22.50 – 3.84
Navarixin Area Under the Plasma Concentration-Time Curve (AUC) From Time 0 to Infinity (AUC0-inf) Secondary · 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)

Plasma samples from participants with selected advanced/metastatic solid tumors were collected to determine the navarixin plasma AUC0-inf

GroupValue95% CI
Navarixin 30 mg + Pembrolizumab 200 mg523± 39.5
Navarixin 100 mg + Pembrolizumab 200 mg1200± 47.5
Navarixin Area Under the Plasma Concentration-Time Curve From Time 0 to Last (AUC0-last) Secondary · 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)

Plasma samples from participants with selected advanced/metastatic solid tumors were collected to determine the navarixin plasma AUC0-last.

GroupValue95% CI
Navarixin 30 mg + Pembrolizumab 200 mg451± 35.7
Navarixin 100 mg + Pembrolizumab 200 mg961± 45.9
Navarixin Maximum Plasma Concentration (Cmax) Secondary · 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)

Plasma samples from participants with selected advanced/metastatic solid tumors were collected to determine the navarixin plasma Cmax.

GroupValue95% CI
Navarixin 30 mg + Pembrolizumab 200 mg172± 53.3
Navarixin 100 mg + Pembrolizumab 200 mg288± 60.6

Adverse events — posted to ClinicalTrials.gov

Time frame: All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Navarixin 30 mg + Pembrolizumab 200 mg
Serious: 17/51 (33%)
Deaths: 48/52
Navarixin 100 mg + Pembrolizumab 200 mg
Serious: 15/54 (28%)
Deaths: 45/55

Serious adverse events (29 terms)

ReactionSystemNavarixin 30 mg + Pembroli…Navarixin 100 mg + Pembrol…
PneumoniaInfections and infestations
ColitisGastrointestinal disorders
Intestinal fistulaGastrointestinal disorders
Intestinal obstructionGastrointestinal disorders
Small intestinal obstructionGastrointestinal disorders
VomitingGastrointestinal disorders
General physical health deteriorationGeneral disorders
PyrexiaGeneral disorders
HepatitisHepatobiliary disorders
Lower respiratory tract infectionInfections and infestations
Pseudomonas infectionInfections and infestations
Urinary tract infectionInfections and infestations
Humerus fractureInjury, poisoning and procedural complications
Spinal compression fractureInjury, poisoning and procedural complications
Aspartate aminotransferase increasedInvestigations
Neutrophil count decreasedInvestigations
Transaminases increasedInvestigations
CachexiaMetabolism and nutrition disorders
HypophosphataemiaMetabolism and nutrition disorders
Cancer painNeoplasms benign, malignant and unspecified (incl cysts and polyps)
EncephalopathyNervous system disorders
Completed suicidePsychiatric disorders
Suicide attemptPsychiatric disorders
Acute kidney injuryRenal and urinary disorders
Renal impairmentRenal and urinary disorders
Other adverse events (41 terms — click to expand)

ReactionSystemNavarixin 30 mg + Pembroli…Navarixin 100 mg + Pembrol…
FatigueGeneral disorders
NauseaGastrointestinal disorders
Decreased appetiteMetabolism and nutrition disorders
PyrexiaGeneral disorders
VomitingGastrointestinal disorders
Neutrophil count decreasedInvestigations
Back painMusculoskeletal and connective tissue disorders
CoughRespiratory, thoracic and mediastinal disorders
NeutropeniaBlood and lymphatic system disorders
Abdominal painGastrointestinal disorders
ArthralgiaMusculoskeletal and connective tissue disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
HeadacheNervous system disorders
PruritusSkin and subcutaneous tissue disorders
AnaemiaBlood and lymphatic system disorders
ConstipationGastrointestinal disorders
DiarrhoeaGastrointestinal disorders
DehydrationMetabolism and nutrition disorders
Weight decreasedInvestigations
AstheniaGeneral disorders
Upper respiratory tract infectionInfections and infestations
Urinary tract infectionInfections and infestations
Aspartate aminotransferase increasedInvestigations
Pain in extremityMusculoskeletal and connective tissue disorders
DysuriaRenal and urinary disorders
RashSkin and subcutaneous tissue disorders
Dry mouthGastrointestinal disorders
Oedema peripheralGeneral disorders
Blood alkaline phosphatase increasedInvestigations
Musculoskeletal chest painMusculoskeletal and connective tissue disorders
HypothyroidismEndocrine disorders
ChillsGeneral disorders
PneumoniaInfections and infestations
Blood creatinine increasedInvestigations
White blood cell count decreasedInvestigations
HypocalcaemiaMetabolism and nutrition disorders
HypokalaemiaMetabolism and nutrition disorders
HypophosphataemiaMetabolism and nutrition disorders
Oropharyngeal painRespiratory, thoracic and mediastinal disorders
Productive coughRespiratory, thoracic and mediastinal disorders

Most-reported serious reactions: Pneumonia, Colitis, Intestinal fistula, Intestinal obstruction, Small intestinal obstruction, Vomiting, General physical health deterioration, Pyrexia.

Data from ClinicalTrials.gov NCT03473925 adverse events section.

Sponsor's own 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).

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Myeloid-derived suppressor cells as immunosuppressive regulators and therapeutic targets in cancer.
    Li K, Shi H, Zhang B, Ou X, et al · · 2021 · cited 687× · PMID 34620838 · DOI 10.1038/s41392-021-00670-9
  2. Elevated serum interleukin-8 is associated with enhanced intratumor neutrophils and reduced clinical benefit of immune-checkpoint inhibitors.
    Schalper KA, Carleton M, Zhou M, Chen T, et al · · 2020 · cited 429× · PMID 32405062 · DOI 10.1038/s41591-020-0856-x
  3. The chemokines CXCL8 and CXCL12: molecular and functional properties, role in disease and efforts towards pharmacological intervention.
    Cambier S, Gouwy M, Proost P. · · 2023 · cited 387× · PMID 36725964 · DOI 10.1038/s41423-023-00974-6
  4. Chemokines Modulate Immune Surveillance in Tumorigenesis, Metastasis, and Response to Immunotherapy.
    Vilgelm AE, Richmond A. · · 2019 · cited 310× · PMID 30873179 · DOI 10.3389/fimmu.2019.00333
  5. Interleukin-8: A chemokine at the intersection of cancer plasticity, angiogenesis, and immune suppression.
    Fousek K, Horn LA, Palena C. · · 2021 · cited 278× · PMID 32980444 · DOI 10.1016/j.pharmthera.2020.107692
  6. Targeting cytokine and chemokine signaling pathways for cancer therapy.
    Yi M, Li T, Niu M, Zhang H, et al · · 2024 · cited 264× · PMID 39034318 · DOI 10.1038/s41392-024-01868-3
  7. Multiple Roles for Chemokines in Neutrophil Biology.
    Capucetti A, Albano F, Bonecchi R. · · 2020 · cited 230× · PMID 32733442 · DOI 10.3389/fimmu.2020.01259
  8. Overcoming immunotherapy resistance in non-small cell lung cancer (NSCLC) - novel approaches and future outlook.
    Horvath L, Thienpont B, Zhao L, Wolf D, et al · · 2020 · cited 204× · PMID 32917214 · DOI 10.1186/s12943-020-01260-z

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