Clinical Trials/NCT02853331

NCT02853331

Completed

Phase 3

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)

Merck Sharp & Dohme LLC0 sites861 target enrollmentSeptember 16, 2016

ConditionsRenal Cell Carcinoma

InterventionsPembrolizumab Axitinib Sunitinib

DrugsAxitinib Sunitinib

Overview

Phase: Phase 3
Intervention: Pembrolizumab
Conditions: Renal Cell Carcinoma
Sponsor: Merck Sharp & Dohme LLC
Enrollment: 861
Primary Endpoint: 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
Status: Completed
Last Updated: 2 months ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Similar Trials

Overview

Brief Summary

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:

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)
The combination therapy of pembrolizumab plus axitinib is superior to sunitinib monotherapy with respect to Overall Survival (OS).

Registry

clinicaltrials.gov

Start Date

September 16, 2016

End Date

December 26, 2025

Last Updated

2 months ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Merck Sharp & Dohme LLC

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Has histologically confirmed diagnosis of RCC with clear cell component with or without sarcomatoid features
•Has locally advanced/metastatic disease (i.e., newly diagnosed Stage IV RCC per American Joint Committee on Cancer) or has recurrent disease
•Has measurable disease per RECIST 1.1 as assessed by the investigator/site radiologist
•Has received no prior systemic therapy for advanced RCC.
•Has provided archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated.
•Has Karnofsky performance status (KPS) ≥ 70% as assessed within 10 days prior to randomization.
•If receiving bone resorptive therapy (including but not limited to bisphosphonate or RANK-L inhibitor) must have therapy initiated at least 2 weeks prior to randomization.
•Demonstrates adequate organ function.
•Female participants of childbearing potential must be willing to use an adequate method of contraception for the course of the study through 120 days after the last dose of study drug.
•Male participants of childbearing potential must agree to use an adequate method of contraception, starting with the first dose of study drug through 120 days after the last dose of study drug.

Exclusion Criteria

•Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to randomization.
•Has had major surgery within 4 weeks, received radiation therapy within 2 weeks prior to randomization, or has not recovered (i.e., ≤ Grade 1 or at baseline) from AEs due to prior treatment.
•Has had prior treatment with any anti-programmed cell death (anti-PD-1), or programmed cell death ligand 1 (PD-L1), or PD-L2 agent or an antibody targeting any other immune-regulatory receptors or mechanisms.
•Has received prior systemic anti-cancer therapy for RCC with vascular endothelial growth factor (VEGF)/VEGF receptors (VEGFR) or mechanistic target of rapamycin (mTOR) targeting agents.
•Has a history of severe hypersensitivity reaction (e.g., generalized rash/erythema, hypotension, bronchospasm, angioedema or anaphylaxis) to axitinib or sunitinib.
•Has a diagnosis of immunodeficiency OR is receiving a systemic steroid therapy exceeding physiologic corticosteroid dose or any other form of immunosuppressive therapy within 7 days prior to randomization, except in the case of central nervous system (CNS) metastases.
•Has an active autoimmune disease requiring systemic treatment with in the past 2 years OR a documented history of clinically severe autoimmune disease. Note: Participants with vitiligo, Sjøgren's syndrome, Type 1 diabetes, resolved childhood asthma/atopy, hypothyroidism or adrenal or pituitary insufficiency who are stable on hormone replacement, are not excluded.
•Has a known additional malignancy that has progressed or has required active treatment in the last 3 years. Note: Basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, or carcinoma in situ such as breast cancer in situ are acceptable if they have undergone potentially curative therapy.
•Has known active CNS metastases and/or carcinomatous meningitis.
•Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis.

Arms & Interventions

Pembrolizumab+Axitinib Combination Therapy

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

Intervention: Pembrolizumab

Pembrolizumab+Axitinib Combination Therapy

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

Intervention: Axitinib

Sunitinib Monotherapy

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

Intervention: Sunitinib

Outcomes

Primary Outcomes

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

Time Frame: Through Database Cutoff Date of 24-Aug-2018 (up to approximately 22 months)

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.

Overall Survival (OS)

Time Frame: Through Database Cutoff Date of 24-Aug-2018 (up to approximately 22 months)

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.

Secondary Outcomes

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(Through Database Cutoff Date of 24-Aug-2018 (up to approximately 22 months))
Number of Participants Who Experienced an Adverse Event (AE)(Through Database Cutoff Date of 24-Aug-2018 (up to approximately 22 months))
Number of Participants Who Discontinued Study Drug Due to an AE(Through Database Cutoff Date of 24-Aug-2018 (up to approximately 22 months))
Overall Survival (OS) Rate at Month 12 in All Participants(Month 12)
Time to True Deterioration (TTD) of the Functional Assessment of Cancer Therapy Kidney Symptom Index Disease-Related Symptoms (FKSI-DRS) Score(Through Database Cutoff Date of 24-Aug-2018 (up to approximately 22 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(Through Database Cutoff Date of 24-Aug-2018 (up to approximately 22 months))
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(Through Database Cutoff Date of 24-Aug-2018 (up to approximately 22 months))
Progression Free Survival Rate (PFS Rate) at Month 24 in All Participants(Month 24)
Overall Survival (OS) Rate at Month 24 in All Participants(Month 24)
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(Baseline (prior to first dose of study treatment in Cycle 1 [cycle length = 21 days]) and Week 54)
Progression Free Survival Rate (PFS Rate) at Month 12 in All Participants(Month 12)
Progression Free Survival Rate (PFS Rate) at Month 18 in All Participants(Month 18)
Overall Survival (OS) Rate at Month 18 in All Participants(Month 18)