Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Digestive System Diseases

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Prostatic Neoplasms

Carcinoma

Colorectal Neoplasms

Carcinoma, Bronchogenic

Bronchial Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Antineoplastic Agents

All Drugs and Chemicals

Pembrolizumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

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

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).

Navarixin

Medical Director

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).

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)

A Phase II Study of Navarixin (MK-7123) in Combination With Pembrolizumab (MK-3475) in Participants With Selected Advanced/Metastatic Solid Tumors

http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

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.

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

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.

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.

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).

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).

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).

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

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

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

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

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.

Merck Sharp & Dohme LLC

All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.

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).

Navarixin 30 mg + Pembrolizumab 200 mg

Navarixin 100 mg + Pembrolizumab 200 mg

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Senior Vice President, Global Clinical Development

All participants with a baseline scan that demonstrated measurable disease by the investigator's assessment, and who were administered at least 1 dose of study medicine.

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

Participants who complete cycle 1 without any discontinuation, or discontinues from the study prior to completing all the safety evaluations in cycle 1 due to treatment-related adverse events, or if participants receive \>=75% of the total pembrolizumab infusion and/or navarixin in cycle, or If the participants experience any DLT in AE.

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

All participants who received at least 1 dose of study treatment.

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

Number of Participants Who Discontinue Study Treatment Due to an AE

iComplete Response (iCR)

iPartial Response (iPR)

All participants with a baseline scan that demonstrated measurable disease by the investigator's assessment, and who were administered at least 1 dose of study medicine. Only participants with progressive disease per RECIST 1.1 are included.

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

CRPC

NSCLC

Progression-free Survival (PFS) Per RECIST 1.1

PFS Per iRECIST

MSCLC

Overall Survival (OS)

Participants who complied with the protocol sufficiently to ensure that their data will be likely to exhibit the effects of treatment, according to the underlying scientific model. Compliance includes such considerations as exposure to treatment, availability of measurements, and the absence of major protocol violations

Absolute Neutrophil Counts (ANC)

Participants with available AUC-inf data, who complied with the protocol sufficiently to ensure that their data was likely to exhibit the effects of treatment, according to the underlying scientific model. Compliance includes, but is not limited to, exposure to treatment, availability of measurements, and absence of major protocol violations.

Navarixin Area Under the Plasma Concentration-Time Curve (AUC) From Time 0 to Infinity (AUC0-inf)

Participants with available AUC-last data, who complied with the protocol sufficiently to ensure that their data was likely to exhibit the effects of treatment, according to the underlying scientific model. Compliance includes, but is not limited to, exposure to treatment, availability of measurements, and absence of major protocol violations.

Navarixin Area Under the Plasma Concentration-Time Curve From Time 0 to Last (AUC0-last)

Participants with available Cmax data, who complied with the protocol sufficiently to ensure that their data was likely to exhibit the effects of treatment, according to the underlying scientific model. Compliance includes, but is not limited to, exposure to treatment, availability of measurements, and absence of major protocol violations.

Navarixin Maximum Plasma Concentration (Cmax)

Participants with available Ctrough data, who complied with the protocol sufficiently to ensure that their data was likely to exhibit the effects of treatment, according to the underlying scientific model. Compliance includes, but is not limited to, exposure to treatment, availability of measurements, and absence of major protocol violations.

Navarixin Trough Plasma Concentration (Ctrough)

Participants received 30 mg navarixin via oral capsules once daily, plus 200 mg pembrolizumab via intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years).

Spots Global Cancer Trial Database for 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)

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

Useful links and downloads for this trial