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NCT02853344

Study of Pembrolizumab (MK-3475) Monotherapy in Locally Advanced/Metastatic Renal Cell Carcinoma (MK-3475-427/KEYNOTE-427)

Completed Phase 2 Results posted Last updated 11 April 2023
What this trial tests

Phase 2 trial testing Pembrolizumab in Renal Cell Carcinoma in 275 participants. Completed in 1 April 2022.

Timeline
30 September 2016
Primary endpoint
5 February 2021
1 April 2022

Quick facts

Lead sponsorMerck Sharp & Dohme LLC
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationnon randomized
Designparallel
Maskingnone
Primary purposetreatment
Enrollment275
Start date30 September 2016
Primary completion5 February 2021
Estimated completion1 April 2022

Drugs / interventions tested

Conditions studied

Sponsor

Merck Sharp & Dohme LLC — full company profile →

Who can join

18 and older, any sex, with Renal Cell Carcinoma. 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) Primary · Up to approximately 52 months

ORR was defined as the percentage of participants who had 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) as assessed by Blinded Independent Central Review (BICR) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1).

GroupValue95% CI
Cohort A: Clear Cell RCC (ccRCC)36.427.4 – 46.1
Cohort B: Non-clear Cell RCC (nccRCC)26.720.1 – 34.1
Duration of Response (DOR) Secondary · Up to approximately 66 months

For participants who demonstrated a confirmed Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, DOR was defined as the time from first documented evidence of a CR or PR until progressive disease (PD) or death. DOR for participants who had not progressed or died at the time of analysis was to be censored at the date of their last tumor assessment. Per RECIST 1.1, PD was defined as at least a 20% increase in the sum of diameters of target lesions as well as an absolute increase o

GroupValue95% CI
Cohort A: Clear Cell RCC (ccRCC)18.92.3 – NA
Cohort B: Non-clear Cell Renal Cell Carcinoma (nccRCC)29.02.8 – NA
Disease Control Rate (DCR) Secondary · Up to approximately 66 months

DCR is defined as the percentage of participants who have achieved CR, PR, or Stable Disease (SD) for at least 6 months based on assessments by the BICR per RECIST 1.1. CR is defined as disappearance of all target lesions, PR is defined as at least a 30% decrease in the sum of diameters of target lesions, SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD): At least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm. The appearance of one or more new lesions is also consi

GroupValue95% CI
Cohort A: Clear Cell RCC (ccRCC)58.248.4 – 67.5
Cohort B: Non-clear Cell Renal Cell Carcinoma (nccRCC)43.035.4 – 51.0
Progression-free Survival (PFS) Secondary · Up to approximately 66 months

PFS is defined as the time from first dose of study treatment to the first documented progressive disease (PD) per RECIST 1.1 based on BICR, or death due to any cause, whichever occurs first. Per RECIST 1.1, PD 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. The appearance of one or more new lesions is also considered PD.

GroupValue95% CI
Cohort A: Clear Cell RCC (ccRCC)7.15.6 – 11.0
Cohort B: Non-clear Cell Renal Cell Carcinoma (nccRCC)4.22.9 – 5.6
Overall Survival Secondary · Up to approximately 66 months

OS was defined as the time from first dose of study treatment to death due to any cause

GroupValue95% CI
Cohort A: Clear Cell RCC (ccRCC)40.731.1 – 52.6
Cohort B: Non-clear Cell Renal Cell Carcinoma (nccRCC)29.924.3 – 37.4
Number of Participants Who Experienced an Adverse Event (AE) Secondary · Up to approximately 27 months

An adverse event is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure.

GroupValue95% CI
Cohort A: Clear Cell RCC (ccRCC)109
Cohort B: Non-clear Cell Renal Cell Carcinoma (nccRCC)155
Number of Participants Who Discontinued Study Drug Due to an AE Secondary · Up to approximately 24 months

An adverse event is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure.

GroupValue95% CI
Cohort A: Clear Cell RCC (ccRCC)23
Cohort B: Non-clear Cell Renal Cell Carcinoma (nccRCC)25

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to approximately 66 months. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Cohort A: ccRCC First Course
Serious: 52/110 (47%)
Deaths: 71/110
Cohort B: nccRCC First Course
Serious: 47/165 (28%)
Deaths: 113/165
Cohort A: ccRCC Second Course
Serious: 0/3 (0%)
Deaths: 0/3
Cohort B: nccRCC Second Course
Serious: 0/5 (0%)
Deaths: 0/5

Serious adverse events (103 terms)

ReactionSystemCohort A: ccRCC First CourseCohort B: nccRCC First Cou…Cohort A: ccRCC Second Cou…Cohort B: nccRCC Second Co…
ColitisGastrointestinal disorders
DiarrhoeaGastrointestinal disorders
HyperglycaemiaMetabolism and nutrition disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
Acute coronary syndromeCardiac disorders
MyocarditisCardiac disorders
PyrexiaGeneral disorders
Autoimmune hepatitisHepatobiliary disorders
CholecystitisHepatobiliary disorders
HepatitisHepatobiliary disorders
PneumoniaInfections and infestations
Urinary tract infectionInfections and infestations
DehydrationMetabolism and nutrition disorders
HyponatraemiaMetabolism and nutrition disorders
Type 1 diabetes mellitusMetabolism and nutrition disorders
Cerebral infarctionNervous system disorders
Acute kidney injuryRenal and urinary disorders
Chronic obstructive pulmonary diseaseRespiratory, thoracic and mediastinal disorders
Pleural effusionRespiratory, thoracic and mediastinal disorders
PneumonitisRespiratory, thoracic and mediastinal disorders
Febrile neutropeniaBlood and lymphatic system disorders
LymphadenopathyBlood and lymphatic system disorders
ThrombocytopeniaBlood and lymphatic system disorders
Acute myocardial infarctionCardiac disorders
Atrial fibrillationCardiac disorders
Other adverse events (54 terms — click to expand)

ReactionSystemCohort A: ccRCC First CourseCohort B: nccRCC First Cou…Cohort A: ccRCC Second Cou…Cohort B: nccRCC Second Co…
FatigueGeneral disorders
PruritusSkin and subcutaneous tissue disorders
DiarrhoeaGastrointestinal disorders
ArthralgiaMusculoskeletal and connective tissue disorders
NauseaGastrointestinal disorders
VomitingGastrointestinal disorders
HypothyroidismEndocrine disorders
CoughRespiratory, thoracic and mediastinal disorders
Decreased appetiteMetabolism and nutrition disorders
ConstipationGastrointestinal disorders
Abdominal painGastrointestinal disorders
Back painMusculoskeletal and connective tissue disorders
AnaemiaBlood and lymphatic system disorders
AstheniaGeneral disorders
Blood creatinine increasedInvestigations
RashSkin and subcutaneous tissue disorders
HeadacheNervous system disorders
PyrexiaGeneral disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
Dry mouthGastrointestinal disorders
Alanine aminotransferase increasedInvestigations
Pain in extremityMusculoskeletal and connective tissue disorders
Oedema peripheralGeneral disorders
Urinary tract infectionInfections and infestations
Blood alkaline phosphatase increasedInvestigations
InsomniaPsychiatric disorders
Aspartate aminotransferase increasedInvestigations
HyperthyroidismEndocrine disorders
NasopharyngitisInfections and infestations
MyalgiaMusculoskeletal and connective tissue disorders
HypertensionVascular disorders
Influenza like illnessGeneral disorders
Weight decreasedInvestigations
DizzinessNervous system disorders
Dry skinSkin and subcutaneous tissue disorders
Rash maculo-papularSkin and subcutaneous tissue disorders
Chest painGeneral disorders
Upper respiratory tract infectionInfections and infestations
Productive coughRespiratory, thoracic and mediastinal disorders
DyspepsiaGastrointestinal disorders

Most-reported serious reactions: Colitis, Diarrhoea, Hyperglycaemia, Dyspnoea, Acute coronary syndrome, Myocarditis, Pyrexia, Autoimmune hepatitis.

Data from ClinicalTrials.gov NCT02853344 adverse events section.

Sponsor's own description

The purpose of this study is to assess the safety and efficacy of monotherapy pembrolizumab (MK-3475) in participants with renal cell carcinoma (RCC). There will be two cohorts in this study: Cohort A will consist of participants with clear cell (cc) RCC and Cohort B will consist of participants with non-clear cell (ncc) RCC.

Publications & conference data

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

  1. The society for immunotherapy of cancer consensus statement on immunotherapy for the treatment of advanced renal cell carcinoma (RCC).
    Rini BI, Battle D, Figlin RA, George DJ, et al · · 2019 · cited 197× · PMID 31856918 · DOI 10.1186/s40425-019-0813-8
  2. Open-Label, Single-Arm, Phase II Study of Pembrolizumab Monotherapy as First-Line Therapy in Patients With Advanced Non-Clear Cell Renal Cell Carcinoma.
    McDermott DF, Lee JL, Ziobro M, Suarez C, et al · · 2021 · cited 177× · PMID 33529058 · DOI 10.1200/jco.20.02365
  3. Open-Label, Single-Arm Phase II Study of Pembrolizumab Monotherapy as First-Line Therapy in Patients With Advanced Clear Cell Renal Cell Carcinoma.
    McDermott DF, Lee JL, Bjarnason GA, Larkin JMG, et al · · 2021 · cited 100× · PMID 33529051 · DOI 10.1200/jco.20.02363
  4. The Clinical Activity of PD-1/PD-L1 Inhibitors in Metastatic Non-Clear Cell Renal Cell Carcinoma.
    McKay RR, Bossé D, Xie W, Wankowicz SAM, et al · · 2018 · cited 95× · PMID 29748390 · DOI 10.1158/2326-6066.cir-17-0475
  5. Immune Checkpoint Inhibitors in Renal Cell Carcinoma: Molecular Basis and Rationale for Their Use in Clinical Practice.
    Lasorsa F, di Meo NA, Rutigliano M, Milella M, et al · · 2023 · cited 91× · PMID 37189689 · DOI 10.3390/biomedicines11041071
  6. Targeting the PD-1/PD-L1 Pathway in Renal Cell Carcinoma.
    Kammerer-Jacquet SF, Deleuze A, Saout J, Mathieu R, et al · · 2019 · cited 64× · PMID 30987368 · DOI 10.3390/ijms20071692
  7. Transcriptomic Determinants of Response to Pembrolizumab Monotherapy across Solid Tumor Types.
    Cristescu R, Nebozhyn M, Zhang C, Albright A, et al · · 2022 · cited 63× · PMID 34965943 · DOI 10.1158/1078-0432.ccr-21-3329
  8. JAK2/PD-L1/PD-L2 (9p24.1) amplifications in renal cell carcinomas with sarcomatoid transformation: implications for clinical management.
    Gupta S, Cheville JC, Jungbluth AA, Zhang Y, et al · · 2019 · cited 59× · PMID 30996253 · DOI 10.1038/s41379-019-0269-x

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