CompletedNCT02853344Updated Apr 11, 2023Results posted

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

A Phase 2 interventional study of Pembrolizumab in Renal Cell Carcinoma, sponsored by Merck Sharp & Dohme LLC. Completed. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2023-04-11.

Sponsored by Merck Sharp & Dohme LLC · Phase 2, Interventional, and Treatment

Phase: Phase 2
Study type: Interventional
Enrollment: 275
Allocation: Non-randomized
Ages: 18 Years and older
Sex: All

Study summary

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.

Conditions studied

Renal Cell Carcinoma

Browse trials for

Keywords

Programmed Cell Death-1 (PD1, PD-1)
Programmed Cell Death 1 Ligand 1(PDL1, PD-L1)
Programmed Cell Death 1 Ligand 2 (PDL2, PD-L2)

In context

Carcinoma

6,741 studies on the registry are indexed under Carcinoma; 1,161 are open to participants now.

This study's enrollment of 275 is above the median of 45 across 5,170 interventional studies indexed under Carcinoma.

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Lead sponsor

Merck Sharp & Dohme LLC is the lead sponsor of 2,114 studies on the registry; 133 are open to participants now.

Of its 489 completed or terminated interventional studies of FDA-regulated products, 362 (74%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years and older
Sexes eligible: All
Accepts healthy volunteers: No

Inclusion criteria

Cohort A (clear cell RCC cohort) participant must have histologically confirmed diagnosis of clear cell RCC or RCC with clear cell component (with or without sarcomatoid features).
Cohort B (non-clear cell RCC cohort) participant must have histologically confirmed diagnosis of non-clear cell RCC (with or without sarcomatoid features). Participants with tumors that have a component of clear cell histology are not eligible for inclusion in Cohort B.
Has locally advanced/metastatic disease, i.e., newly diagnosed Stage IV RCC per American Joint Committee on Cancer (AJCC) or have recurrent disease.
Has measurable disease per RECIST 1.1 as assessed by BICR.
Has received no prior systemic therapy for advanced RCC. Prior neoadjuvant/adjuvant therapy for RCC is acceptable if completed >12 months prior to allocation.
Must provide adequate tissue for biomarker analysis for Cohorts A and B from an archival tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated.
Participants receiving bone resorptive therapy (including but not limited to bisphosphonate or RANK-L inhibitor) must have therapy initiated at least 2 weeks prior to treatment allocation.
Has Karnofsky Performance Status (KPS) ≥70%, as assessed within 10 days prior to treatment allocation.
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

Exclusion Criteria:

Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks prior to allocation, has had major surgery within 4 weeks or radiation therapy within 2 weeks prior to allocation, or who has not recovered (i.e., ≤ Grade 1 or to Baseline) from AEs due to prior treatment.
Had prior treatment with any anti-programmed cell death 1 (anti-PD-1), or anti-programmed cell death ligand 1 (PD-L1), or PD-L2 agent or an antibody targeting any other immune-regulatory receptors or mechanisms. Examples of such antibodies include antibodies against indoleamine-2,3-dioxygenase (IDO), PD-L1, interleukin 2 receptors (IL-2R), glucocorticoid-induced tumor necrosis factor receptor-related protein (GITR).
Has a diagnosis of immunodeficiency OR is receiving a systemic steroid therapy exceeding 10 mg daily dose of prednisone or equivalent or any other form of immunosuppressive therapy within 7 days prior to allocation, except in the case of central nervous system (CNS) metastases (see below).
Has an active autoimmune disease requiring systemic treatment within the past 2 years OR a documented history of clinically severe autoimmune disease.
Has a known additional malignancy that has had progression or has required active treatment in the last 3 years. Note: Basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ, such as breast cancer in situ, that has undergone potentially curative therapy are acceptable.
Has known active CNS metastases and/or carcinomatous meningitis.
Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis.
Has an active infection requiring systemic therapy.
Has a known history of Human Immunodeficiency Virus (HIV) infection.
Has known history of Hepatitis B or known active Hepatitis C.
Has received a live virus vaccine within 30 days of allocation.
Has had a prior solid organ transplant.
Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of study drug.

Study design

Phase: Phase 2
Primary purpose: Treatment
Allocation: Non-randomized
Intervention model: Parallel assignment
Masking: None (open label)
Enrollment: 275 participants (actual)

Study arms

Experimental
Cohort A: Clear Cell RCC
Participants with clear cell RCC receive pembrolizumab 200 mg intravenously (IV) every 3 weeks (Q3W) for up to 35 doses (approximately 24 months).
Biological: Pembrolizumab
Experimental
Cohort B: Non-clear Cell RCC
Participants with non-clear cell RCC receive pembrolizumab 200 mg IV Q3W for up to 35 doses (approximately 24 months).
Biological: Pembrolizumab

Interventions

BiologicalPembrolizumab
IV infusion
Also known as: MK-3475, KEYTRUDA®

What researchers measure

Primary outcomes

Objective Response Rate (ORR)
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).
Time frame: Up to approximately 52 months

Secondary outcomes

Duration of Response (DOR)
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 of at least 5 mm in the sum of diameters. The appearance of one or more new lesions was also considered PD. DOR assessments were based on BICR with confirmation. The DOR as assessed using RECIST 1.1 for all participants who experienced a confirmed CR or PR is presented.
Time frame: Up to approximately 66 months
Disease Control Rate (DCR)
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 considered PD.
Time frame: Up to approximately 66 months
Progression-free Survival (PFS)
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.
Time frame: Up to approximately 66 months
Overall Survival
OS was defined as the time from first dose of study treatment to death due to any cause
Time frame: Up to approximately 66 months
Number of Participants Who Experienced an Adverse Event (AE)
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.
Time frame: Up to approximately 27 months
Number of Participants Who Discontinued Study Drug Due to an AE
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.
Time frame: Up to approximately 24 months

Results

Posted May 11, 2022

Participant flow

Participant flow — Overall Study
Milestone	Cohort A: Clear Cell Renal Cell Carcinoma (ccRCC)	Cohort B: Non-clear Cell RCC (nccRCC)
Started	110	165
Received second course of pembrolizumab	3	5
Completed	0	0
Not completed	110	165
Withdrew: Lost to follow-up	1	1
Withdrew: Withdrawal by subject	2	4
Withdrew: Participation in study terminated by sponsor	37	48
Withdrew: Death	70	112

Outcome measures

PrimaryObjective Response Rate (ORR)

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).

Time frame:: Up to approximately 52 months
Reported as:: Number · Percentage of Participants

Objective Response Rate (ORR)
Percentage of Participants	Cohort A: Clear Cell RCC (ccRCC)	Cohort B: Non-clear Cell RCC (nccRCC)
Objective Response Rate (ORR)	36.4 (27.4 to 46.1)	26.7 (20.1 to 34.1)

SecondaryDuration of Response (DOR)

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 of at least 5 mm in the sum of diameters. The appearance of one or more new lesions was also considered PD. DOR assessments were based on BICR with confirmation. The DOR as assessed using RECIST 1.1 for all participants who experienced a confirmed CR or PR is presented.

Time frame:: Up to approximately 66 months
Reported as:: Median · Months

Duration of Response (DOR)
Months	Cohort A: Clear Cell RCC (ccRCC)	Cohort B: Non-clear Cell Renal Cell Carcinoma (nccRCC)
Duration of Response (DOR)	18.9 (2.3 to NA)	29.0 (2.8 to NA)

SecondaryDisease Control Rate (DCR)

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 considered PD.

Time frame:: Up to approximately 66 months
Reported as:: Number · Percentage of Participants

Disease Control Rate (DCR)
Percentage of Participants	Cohort A: Clear Cell RCC (ccRCC)	Cohort B: Non-clear Cell Renal Cell Carcinoma (nccRCC)
Disease Control Rate (DCR)	58.2 (48.4 to 67.5)	43.0 (35.4 to 51.0)

SecondaryProgression-free Survival (PFS)

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.

Time frame:: Up to approximately 66 months
Reported as:: Median · Months

Progression-free Survival (PFS)
Months	Cohort A: Clear Cell RCC (ccRCC)	Cohort B: Non-clear Cell Renal Cell Carcinoma (nccRCC)
Progression-free Survival (PFS)	7.1 (5.6 to 11.0)	4.2 (2.9 to 5.6)

SecondaryOverall Survival

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

Time frame:: Up to approximately 66 months
Reported as:: Median · Months

Overall Survival
Months	Cohort A: Clear Cell RCC (ccRCC)	Cohort B: Non-clear Cell Renal Cell Carcinoma (nccRCC)
Overall Survival	40.7 (31.1 to 52.6)	29.9 (24.3 to 37.4)

SecondaryNumber of Participants Who Experienced an Adverse Event (AE)

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.

Time frame:: Up to approximately 27 months
Reported as:: Count of participants · Participants

Number of Participants Who Experienced an Adverse Event (AE)
Participants	Cohort A: Clear Cell RCC (ccRCC)	Cohort B: Non-clear Cell Renal Cell Carcinoma (nccRCC)
Number of Participants Who Experienced an Adverse Event (AE)	109	155

SecondaryNumber of Participants Who Discontinued Study Drug Due to an AE

Time frame:: Up to approximately 24 months
Reported as:: Count of participants · Participants

Number of Participants Who Discontinued Study Drug Due to an AE
Participants	Cohort A: Clear Cell RCC (ccRCC)	Cohort B: Non-clear Cell Renal Cell Carcinoma (nccRCC)
Number of Participants Who Discontinued Study Drug Due to an AE	23	25

Adverse events

Collected over Up to approximately 66 months. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Cohort A: ccRCC First Course	71/110 (64.5%)	52/110 (47.3%)	105/110 (95.5%)
Cohort B: nccRCC First Course	113/165 (68.5%)	47/165 (28.5%)	142/165 (86.1%)
Cohort A: ccRCC Second Course	0/3 (0%)	0/3 (0%)	3/3 (100%)
Cohort B: nccRCC Second Course	0/5 (0%)	0/5 (0%)	3/5 (60%)

Most frequent serious events

Showing 10 of 103

Most frequent serious events
Event	Cohort A: ccRCC First Course	Cohort B: nccRCC First Course	Cohort A: ccRCC Second Course	Cohort B: nccRCC Second Course
ColitisGastrointestinal disorders	4/110	3/165	0/3	0/5
DiarrhoeaGastrointestinal disorders	4/110	0/165	0/3	0/5
HyperglycaemiaMetabolism and nutrition disorders	3/110	0/165	0/3	0/5
Acute coronary syndromeCardiac disorders	2/110	1/165	0/3	0/5
PyrexiaGeneral disorders	2/110	1/165	0/3	0/5
CholecystitisHepatobiliary disorders	2/110	0/165	0/3	0/5
HepatitisHepatobiliary disorders	2/110	0/165	0/3	0/5
PneumoniaInfections and infestations	2/110	2/165	0/3	0/5
Urinary tract infectionInfections and infestations	2/110	1/165	0/3	0/5
DehydrationMetabolism and nutrition disorders	2/110	1/165	0/3	0/5

Most frequent other events

Showing 10 of 54

Most frequent other events
Event	Cohort A: ccRCC First Course	Cohort B: nccRCC First Course	Cohort A: ccRCC Second Course	Cohort B: nccRCC Second Course
FatigueGeneral disorders	43/110	42/165	0/3	0/5
PruritusSkin and subcutaneous tissue disorders	41/110	37/165	0/3	1/5
ArthralgiaMusculoskeletal and connective tissue disorders	37/110	29/165	1/3	0/5
ConstipationGastrointestinal disorders	23/110	18/165	1/3	0/5
Catheter site painGeneral disorders	0/110	2/165	1/3	0/5
HypersensitivityImmune system disorders	0/110	0/165	1/3	0/5
SinusitisInfections and infestations	6/110	3/165	1/3	0/5
Neutrophil count decreasedInvestigations	1/110	3/165	1/3	0/5
Groin painMusculoskeletal and connective tissue disorders	1/110	1/165	1/3	0/5
WheezingRespiratory, thoracic and mediastinal disorders	2/110	1/165	1/3	0/5

Baseline characteristics

Age, Continuous
Age, Continuous(Years)	Cohort A: Clear Cell Renal Cell Carcinoma (ccRCC)	Cohort B: Non-clear Cell RCC (nccRCC)	Total
Mean	62.9 ± 11.0	60.0 ± 12.3	61.1 ± 11.8

Sex: Female, Male
Sex: Female, Male(Participants)	Cohort A: Clear Cell Renal Cell Carcinoma (ccRCC)	Cohort B: Non-clear Cell RCC (nccRCC)	Total
Female	24	56	80
Male	86	109	195

Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)	Cohort A: Clear Cell Renal Cell Carcinoma (ccRCC)	Cohort B: Non-clear Cell RCC (nccRCC)	Total
Hispanic or Latino	2	1	3
Not Hispanic or Latino	104	156	260
Unknown or Not Reported	4	8	12

Race (NIH/OMB)
Race (NIH/OMB)(Participants)	Cohort A: Clear Cell Renal Cell Carcinoma (ccRCC)	Cohort B: Non-clear Cell RCC (nccRCC)	Total
American Indian or Alaska Native	1	1	2
Asian	11	17	28
Native Hawaiian or Other Pacific Islander	0	0	0
Black or African American	0	1	1
White	98	145	243
More than one race	0	0	0
Unknown or Not Reported	0	1	1

Study locations

No study locations are listed for this record.

References and documents

Publications

McDermott DF, Lee JL, Bjarnason GA, Larkin JMG, Gafanov RA, Kochenderfer MD, Jensen NV, Donskov F, Malik J, Poprach A, Tykodi SS, Alonso-Gordoa T, Cho DC, Geertsen PF, Climent Duran MA, DiSimone C, Silverman RK, Perini RF, Schloss C, Atkins MB. Open-Label, Single-Arm Phase II Study of Pembrolizumab Monotherapy as First-Line Therapy in Patients With Advanced Clear Cell Renal Cell Carcinoma. J Clin Oncol. 2021 Mar 20;39(9):1020-1028. doi: 10.1200/JCO.20.02363. Epub 2021 Feb 2. PubMed 33529051 ↗
McDermott DF, Lee JL, Ziobro M, Suarez C, Langiewicz P, Matveev VB, Wiechno P, Gafanov RA, Tomczak P, Pouliot F, Donskov F, Alekseev BY, Shin SJ, Bjarnason GA, Castellano D, Silverman RK, Perini RF, Schloss C, Atkins MB. Open-Label, Single-Arm, Phase II Study of Pembrolizumab Monotherapy as First-Line Therapy in Patients With Advanced Non-Clear Cell Renal Cell Carcinoma. J Clin Oncol. 2021 Mar 20;39(9):1029-1039. doi: 10.1200/JCO.20.02365. Epub 2021 Feb 2. PubMed 33529058 ↗

Study documents

Protocol and statistical analysis plan · May 25, 2021

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes — http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Apr 11, 2023, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT02853344
Lead sponsor: Merck Sharp & Dohme LLC
Responsible party: Sponsor
First posted: Aug 2, 2016
Start date: Sep 30, 2016
Primary completion: Feb 5, 2021
Completion: Apr 1, 2022
Results posted: May 11, 2022
Last update: Apr 11, 2023

Study contacts

Medical Director

study director · Merck Sharp & Dohme LLC

Oversight

Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

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