Neoplasms

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Rare Diseases

Carcinoma

Carcinoma, Renal Cell

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

Kidney Neoplasms

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Kidney Diseases

Urologic Diseases

Male Urogenital Diseases

Renal Cell Carcinoma

Clear Cell Renal Cell Carcinoma

Antineoplastic Agents

All Drugs and Chemicals

Pembrolizumab

Axitinib

Sunitinib

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Angiogenesis Inhibitors

Growth Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Participants receive pembrolizumab 200 mg intravenously every 3 weeks PLUS axitinib 5 mg orally twice daily.

Participants receive sunitinib 50 mg orally once daily for 4 weeks and then are off treatment for 2 weeks.

Medical Director

The purpose of this study is to evaluate the efficacy and safety of pembrolizumab (MK-3475) in combination with axitinib versus sunitinib monotherapy as a first-line treatment for participants with advanced/metastatic renal cell carcinoma (mRCC).

The primary hypotheses of this study are:

1. The combination therapy of pembrolizumab plus axitinib is superior to sunitinib monotherapy with respect to Progression-Free Survival (PFS) as assessed by blinded independent central imaging review per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1)
2. The combination therapy of pembrolizumab plus axitinib is superior to sunitinib monotherapy with respect to Overall Survival (OS).

Study to Evaluate the Efficacy and Safety of Pembrolizumab (MK-3475) in Combination With Axitinib Versus Sunitinib Monotherapy in Participants With Renal Cell Carcinoma (MK-3475-426/KEYNOTE-426)

A Phase III Randomized, Open-label Study to Evaluate Efficacy and Safety of Pembrolizumab (MK-3475) in Combination With Axitinib Versus Sunitinib Monotherapy as a First-line Treatment for Locally Advanced or Metastatic Renal Cell Carcinoma (mRCC) (KEYNOTE-426)

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

EORTC QLQ-C30 is a questionnaire that rates the overall quality of life in cancer participants. The first 28 questions use a 4-point scale (1=not at all to 4=very much) for evaluating function (physical, role, social, cognitive, emotional), symptoms (diarrhea, fatigue, dyspnea, appetite loss, insomnia, nausea/vomiting, constipation, and pain) and financial difficulties. The last 2 questions use a 7-point scale (1=very poor to 7=excellent) to evaluate overall health and quality of life. Global scores are converted to a score of 0 to 100, with a higher score indicating improved health status. The mean baseline EORTC QLQ-C30 score is presented.

PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. The PFS per RECIST 1.1 was calculated using the product-limit (Kaplan-Meier) method for censored data. The PFS for participants is presented.

OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the interim analysis were censored at the date of the last follow up. The OS was calculated using the product-limit (Kaplan-Meier) method for censored data. The OS for participants is presented.

ORR was determined per RECIST 1.1 and was defined as the percentage of participants in the analysis population who had a Complete Response (CR: disappearance of all target lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters) per RECIST 1.1. The ORR was calculated using the Miettinen \& Nurminen method stratified by International Metastatic Renal Cell Carcinoma (RCC) Database Consortium (IMDC) risk group (favorable vs. intermediate vs. poor) and geographic region (North America vs. Western Europe vs. Rest of World). The percentage of participants who experienced a CR or PR is presented.

DCR was defined as the percentage of participants who had a Complete Response (CR: Disappearance of all target lesions), Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters), or Stable Disease (SD) per RECIST 1.1 for ≥6 months. The DCR was calculated using the Miettinen \& Nurminen method stratified by International Metastatic Renal Cell Carcinoma (RCC) Database Consortium (IMDC) risk group (favorable vs. intermediate vs. poor) and geographic region (North America vs. Western Europe vs. Rest of World). The percentage of participants who experienced a CR, PR, or SD is presented.

DOR was defined as the time from first documented evidence of a Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters) per RECIST 1.1 until progressive disease (PD) or death due to any cause, whichever occurred first. PD was defined per RECIST 1.1 as ≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. The DOR was calculated using the product-limit (Kaplan-Meier) method for censored data. The DOR for all participants who experienced a CR or PR is presented.

An AE was defined as any untoward medical occurrence in a participant administered a study treatment and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the study treatment or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that was temporally associated with the use of study treatment, was also an AE. The number of participants who experienced at least one AE is presented.

An AE was defined as any untoward medical occurrence in a participant administered a study treatment and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the study treatment or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that was temporally associated with the use of study treatment, was also an AE. The number of participants who discontinued study treatment due to an AE is presented.

The PFS rate was determined in all participants at Month 12. PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first. Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1), PD was defined as ≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. The date of PD was approximated by the date of the first assessment at which PD was documented per RECIST 1.1 by Blinded Independent Central Review (BICR). Death was always considered as confirmed PD. Participants who did not experience PFS were censored at the last disease assessment. The PFS rate at Month 12 is presented.

The PFS rate was determined in all participants at Month 18. PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first. Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1), PD was defined as ≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. The date of PD was approximated by the date of the first assessment at which PD was documented per RECIST 1.1 by Blinded Independent Central Review (BICR). Death was always considered as confirmed PD. Participants who did not experience PFS were censored at the last disease assessment. The PFS rate at Month 18 is presented.

The PFS rate was determined in all participants at Month 24. PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first. Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1), PD was defined as ≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. The date of PD was approximated by the date of the first assessment at which PD was documented per RECIST 1.1 by Blinded Independent Central Review (BICR). Death was always considered as confirmed PD. Participants who did not experience PFS were censored at the last disease assessment.

The OS rate was determined for all participants at Month 12 and was defined as the time from randomization to death due to any cause. Participants were censored at the date of their last assessment. The OS rate at Month 12 is presented.

The OS rate was determined for all participants at Month 18 and was defined as the time from randomization to death due to any cause. Participants were censored at the date of their last assessment. The OS rate at Month 18 is presented.

The OS rate was determined for all participants at Month 24 and was defined as the time from randomization to death due to any cause. Participants were censored at the date of their last assessment.

TTD was defined as time (in months) from the first dose of study treatment to the date of deterioration of FKSI-DRS Score. The FKSI-DRS was a questionnaire that asked the participant to rate 9 kidney cancer-related symptoms: lack of energy, fatigue, weight loss, pain, bone pain, shortness of breath, cough, fever, or blood in the urine. Each item was scored on a 5-point scale (0=not at all to 4=very much). FKSI-DRS total score ranged from 0 (most severe symptoms) to 36 (no symptoms) with a higher score indicating a better outcome. Deterioration was defined as a 3-point decrease (i.e. lower score) in symptom score and the time to true deterioration was the time to first onset of 3 or more decreases from baseline with confirmation under right-censoring rule (the last observation). The time to true deterioration as measured in months is presented.

EORTC QLQ-C30 is a questionnaire that rates the overall quality of life in cancer participants. The first 28 questions use a 4-point scale (1=not at all to 4=very much) for evaluating function (physical, role, social, cognitive, emotional), symptoms (diarrhea, fatigue, dyspnea, appetite loss, insomnia, nausea/vomiting, constipation, and pain) and financial difficulties. The last 2 questions use a 7-point scale (1=very poor to 7=excellent) to evaluate overall health and quality of life. Global scores are converted to a score of 0 to 100, with a higher score indicating improved health status.

Merck Sharp & Dohme LLC

Population: All participants who received ≥1 dose of study treatment. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" \& "Disease progression" not related to study drug are excluded as AEs.

Participants received pembrolizumab 200 mg intravenously every 3 weeks PLUS axitinib 5 mg orally twice daily.

Pembrolizumab + Axitinib

Participants received sunitinib 50 mg orally once daily for 4 weeks and then were off treatment for 2 weeks.

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Favorable

Intermediate

Poor

Participants were stratified by IMDC risk group using the following criteria: baseline Karnofsky Performance Status \<80%; interval between initial diagnosis of renal cell carcinoma to start of first-line systemic treatment for advanced disease \<1year; baseline hemoglobin \<lower limit of normal (LLN); baseline platelet count \>upper limit of normal (ULN); baseline corrected calcium1 \>ULN; and baseline neutrophil \>ULN. The category was determined by totaling the risk factors per participant and scored as favorable (no factors); intermediate (1 or 2 factors); and poor (≥3 factors).

International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) Risk Group

North America

Western Europe

Rest of World

Participants were stratified by geographic region using the following categories: North America; Western Europe; and Rest of the World.

Geographic Region

Senior Vice President, Global Clinical Development

The analysis population consisted of all randomized participants.

Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Imaging Review

Overall Survival (OS)

Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Imaging Review

The analysis population consisted of all randomized participants who experienced a PR, CR or SD for ≥6 months.

Disease Control Rate (DCR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Imaging Review

The analysis population consisted of all randomized participants who experienced a CR or PR.

Duration of Response (DOR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Imaging Review

The analysis population consisted of all participants who received ≥1 dose of study treatment.

Number of Participants Who Experienced an Adverse Event (AE)

Number of Participants Who Discontinued Study Drug Due to an AE

Progression Free Survival Rate (PFS Rate) at Month 12 in All Participants

Progression Free Survival Rate (PFS Rate) at Month 18 in All Participants

Progression Free Survival Rate (PFS Rate) at Month 24 in All Participants

Overall Survival (OS) Rate at Month 12 in All Participants

Overall Survival (OS) Rate at Month 18 in All Participants

Overall Survival (OS) Rate at Month 24 in All Participants

All randomized participants who received at least 1 dose of study medication and completed at least 1 questionnaire assessment.

Time to True Deterioration (TTD) of the Functional Assessment of Cancer Therapy Kidney Symptom Index Disease-Related Symptoms (FKSI-DRS) Score

Least Squares (LS) Mean Change From Baseline to Week 54 in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Global Health Status (GHS) Scale Score

All participants with non-missing questionnaire assessments at baseline.

Mean Baseline EORTC Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Score

EORTC QLQ-C30 is a cancer-specific instrument with 30 questions used to assess the overall quality of life (QOL) in cancer participants. The first 28 questions used a 4-point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much) for evaluating 5 functional scales (physical, role, social, cognitive, emotional), 8 symptom scales/items (diarrhea, fatigue, dyspnea, appetite loss, insomnia, nausea and vomiting \[N/V\], constipation, and pain) and a single item (financial difficulties). The last 2 questions represented the participant's assessment of overall health and quality of life on a 7-point scale (1=very poor to 7=excellent). EORTC QLQ-C30 global scores were linearly transformed on a scale of 0 to 100; with a high score indicating improved health status. Negative change from baseline values indicated deterioration in health status or functioning and positive changes indicated improvement. The LS Mean change from baseline to Week 30 is presented.

All participants who received at least 1 dose of study medication and had non-missing questionnaire assessments at baseline and Week 30.

Least Squares (LS) Mean Change From Baseline to Week 30 in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Global Health Status (GHS) Scale Score

Spots Global Cancer Trial Database for Study to Evaluate the Efficacy and Safety of Pembrolizumab (MK-3475) in Combination With Axitinib Versus Sunitinib Monotherapy in Participants With Renal Cell Carcinoma (MK-3475-426/KEYNOTE-426)

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Study Description

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