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TerminatedNCT02212730Updated Jul 16, 2020Results posted

A Study Evaluating the Effect of Pembrolizumab (MK-3475) in Participants With Renal Cell Cancer (MK-3475-031)

A Phase 1 interventional study of Pembrolizumab Pre-Resection and Surgical Resection in Renal Cell Cancer, sponsored by Merck Sharp & Dohme LLC. Terminated. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2020-07-16.

Sponsored by Merck Sharp & Dohme LLC · Phase 1, Interventional, and Treatment

Why this study was terminated
Terminated early due to low enrollment
Phase
Phase 1
Study type
Interventional
Enrollment
10
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study summary

This study will examine the effect of treatment with the neoadjuvant antibody pembrolizumab (MK-3475) on tumors of participants with renal cell cancer (RCC). The primary hypotheses are that pembrolizumab is well tolerated in participants undergoing RCC tumor resection; and that pembrolizumab will stimulate a 2-fold or greater increase in intratumoral lymphocytic infiltration in at least 30% of participants with RCC.

02

Conditions studied

  • Renal Cell Cancer
03

In context

Carcinoma, Renal Cell

1,965 studies on the registry are indexed under Carcinoma, Renal Cell; 378 are open to participants now.

This study's enrollment of 10 is below the median of 42 across 1,480 interventional studies indexed under Carcinoma, Renal Cell.

Browse Carcinoma, Renal Cell studies →

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.

04

Who can participate

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

Inclusion criteria

  • Have a newly diagnosed RCC, with a primary tumor diameter of more than 4 cm (>= T1b), not previously treated, and be a candidate for operative tumor resection
  • Be willing and able to undergo pre-treatment baseline image-guided core biopsy of their primary RCC
  • Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale
  • Demonstrate adequate organ function
  • Female is not breast feeding, is postmenopausal or surgically sterile; demonstrates non-pregnant state, and agrees to use two acceptable methods of birth control throughout the trial, until 120 days after the last dose of treatment
  • Male with female partner of childbearing potential agrees to use adequate method of contraception throughout study, until 120 days after last dose of treatment or last blood draw.

Exclusion criteria

Exclusion Criteria:

  • Is currently participating in, or has participated in a study with an investigational agent or device within 4 weeks prior to first dose of study therapy
  • Has a diagnosis of immunosuppression or has received systemic steroid therapy, or any other form of immunosuppressive therapy within 4 weeks prior to first dose of study therapy
  • Has had prior chemotherapy, targeted small molecule, or radiation therapy for treatment of RCC
  • Has a known additional (other than RCC) malignancy that is progressing or requires active treatment
  • Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
  • Has an active, or documented history of autoimmune disease, with the exceptions of vitiligo or resolved childhood asthma/atopy
  • Has a history of (non-infectious) pneumonitis that required treatment with steroids or current pneumonitis.
  • Has an active infection requiring systematic therapy
  • Is receiving anticoagulant therapy, with the exception of low dosage aspirin
  • Has severe cardiovascular disease or symptomatic ischemic heart disease
  • Has hepatic decompensation
  • Has uncontrolled thyroid dysfunction
  • Has uncontrolled diabetes mellitus
  • Has known psychiatric or substance abuse disorders
  • Female is pregnant or breastfeeding
  • Is expecting to conceive children within the projected maximum duration of the trial, extending through 120 days after the last dose of treatment or the last blood draw
  • Has received prior therapy with any antibody or drug (including ipilimumab) specifically targeting T-cell co-stimulation or checkpoint pathway
  • Has a known history of human immunodeficiency virus (HIV)
  • Has known active hepatitis B or C
  • Has received a live vaccine within 30 days prior to screening
05

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
10 participants (actual)

Study arms

  • Experimental
    Neoadjuvant Pembrolizumab + RCC Resection

    Participants received pembrolizumab, 200 mg intravenously (IV) once every 3-week cycle for up to 2 cycles followed by standard of care (SOC) renal cell carcinoma (RCC) surgical resection; and then received post-resection pembrolizumab 200 mg IV once every 3 week cycle for up to approximately 1 year (17 cycles). Post-resection pembrolizumab was only administered to participants who enrolled after Protocol Amendment 04.

    Drug: Pembrolizumab Pre-Resection · Procedure: Surgical Resection · Drug: Pembrolizumab Post-Resection

  • Experimental
    RCC Resection

    Participants received SOC renal cell carcinoma (RCC) surgical resection; and then may have received post-resection pembrolizumab 200 mg IV once every 3 week cycle for up to approximately 1 year (17 cycles). Post-resection pembrolizumab was only administered to participants who enrolled under Protocol Amendment 04.

    Procedure: Surgical Resection · Drug: Pembrolizumab Post-Resection

Interventions

  • DrugPembrolizumab Pre-Resection

    200 mg administered by IV, once every 3-week cycle for a maximum of 2 cycles

    Also known as: KEYTRUDA®, MK-3475

  • ProcedureSurgical Resection

    Standard of care surgical resection of RCC tumor

  • DrugPembrolizumab Post-Resection

    200 mg administered by IV, once every 3-week cycle for a maximum of 17 cycles

    Also known as: KEYTRUDA®, MK-3475

06

What researchers measure

Primary outcomes

  1. Number of Participants With an Adverse Event (AE) During the Neoadjuvant Pembrolizumab Regimen

    An AE was defined as any untoward medical occurrence in a participant administered study treatment and which did not necessarily have to have a causal relationship with this treatment. The number of participants who experienced an AE during their regimen of neoadjuvant pembrolizumab was presented.

    Time frame: Up to Week 16

  2. Number of Participants Who Discontinued Treatment Due to an Adverse Event

    An AE was defined as any untoward medical occurrence in a participant administered study treatment and which did not necessarily have to have a causal relationship with this treatment. The number of participants who discontinued study drug due to an adverse event is presented.

    Time frame: Up to 56 weeks

  3. Number of Participants Treated With Neoadjuvant Pembrolizumab With a 2-fold or Greater Change From Baseline in Intratumoral CD3+ Lymphocytic Infiltration

    The number of participants who received neoadjuvant pembrolizumab and showed a 2-fold or greater change from baseline in intratumoral CD3+ lymphocytic infiltration is presented. Evaluations were based on pathologist score.

    Time frame: Baseline and Week 7

  4. Number of Participants Treated With Neoadjuvant Pembrolizumab With a 2-fold or Greater Change From Baseline in Intratumoral CD8+ Lymphocytic Infiltration

    The number of participants who received neoadjuvant pembrolizumab and showed a 2-fold or greater change from baseline in intratumoral CD8+ lymphocytic infiltration is presented. Evaluations were based on pathologist score.

    Time frame: Baseline and Week 7

  5. Number of Participants Treated With Neoadjuvant Pembrolizumab With a 2-fold or Greater Change From Baseline in Intratumoral FoxP3+ Lymphocytic Infiltration

    The number of participants who received neoadjuvant pembrolizumab and showed a 2-fold or greater change from baseline in intratumoral FoxP3+ (forkhead box protein P3 positive) lymphocytic infiltration is presented. Evaluations were based on pathologist score.

    Time frame: Baseline and Week 7

Secondary outcomes

  1. Change From Baseline in Levels of Gene Expression of Immune Modulatory Receptors in Tumors of Participants Treated With Neoadjuvant Pembrolizumab

    The change from baseline in levels of gene expression of immune modulatory receptors in tumors of participants treated with neoadjuvant pembrolizumab was presented.

    Time frame: Baseline and Week 7

  2. Change From Baseline in Number of T Cells in Tumors of Participants Treated With Neoadjuvant Pembrolizumab

    The change from baseline in number of T cells in tumors of participants treated with neoadjuvant pembrolizumab was presented.

    Time frame: Baseline and Week 7

  3. Change From Baseline in Number of Activated T Cells in Peripheral Blood of Participants Treated With Neoadjuvant Pembrolizumab

    The change from baseline in the number of activated T cells in peripheral blood of participants treated with neoadjuvant pembrolizumab was presented.

    Time frame: Baseline and Week 7

  4. Change From Baseline in Levels of Programmed Cell Death 1 Ligand 1 (PD-L1) Protein in Tumors of Participants Treated With Neoadjuvant Pembrolizumab

    The change from baseline in levels of programmed cell death 1 ligand 1 (PD-L1) protein in tumors of participants treated with neoadjuvant pembrolizumab in participants who received neoadjuvant pembrolizumab was presented.

    Time frame: Baseline and Week 7

  5. Change From Baseline in Levels of Programmed Cell Death 1 Ligand 2 (PD-L2) Protein in Tumors of Participants Treated With Neoadjuvant Pembrolizumab

    The change from baseline in levels of programmed cell death 1 ligand 2 (PD-L2) protein in tumors of participants treated with neoadjuvant pembrolizumab in participants who received neoadjuvant pembrolizumab was presented.

    Time frame: Baseline and Week 7

07

Results

Posted Jul 16, 2020

Participant flow

Participant flow — Overall Study
MilestoneNeoadjuvant Pembrolizumab + RCC ResectionRCC Resection
Started64
Received neoadjuvant pembrolizumab40
Underwent rcc43
Received post-rcc pembrolizumab11
Completed43
Not completed21
Withdrew: Tumor not of the required cell histology10
Withdrew: Withdrawal by subject10
Withdrew: Disease progression prior to rcc surgery01

Outcome measures

PrimaryNumber of Participants With an Adverse Event (AE) During the Neoadjuvant Pembrolizumab Regimen

An AE was defined as any untoward medical occurrence in a participant administered study treatment and which did not necessarily have to have a causal relationship with this treatment. The number of participants who experienced an AE during their regimen of neoadjuvant pembrolizumab was presented.

Time frame:
Up to Week 16
Reported as:
Count of participants · Participants
Number of Participants With an Adverse Event (AE) During the Neoadjuvant Pembrolizumab Regimen
ParticipantsNeoadjuvant Pembrolizumab + RCC Resection
Number of Participants With an Adverse Event (AE) During the Neoadjuvant Pembrolizumab Regimen4
PrimaryNumber of Participants Who Discontinued Treatment Due to an Adverse Event

An AE was defined as any untoward medical occurrence in a participant administered study treatment and which did not necessarily have to have a causal relationship with this treatment. The number of participants who discontinued study drug due to an adverse event is presented.

Time frame:
Up to 56 weeks
Reported as:
Count of participants · Participants
Number of Participants Who Discontinued Treatment Due to an Adverse Event
ParticipantsNeoadjuvant Pembrolizumab + RCC ResectionRCC Resection
During neoadjuvant pembrolizumab00
During post-RCC resection pembrolizumab10
PrimaryNumber of Participants Treated With Neoadjuvant Pembrolizumab With a 2-fold or Greater Change From Baseline in Intratumoral CD3+ Lymphocytic Infiltration

The number of participants who received neoadjuvant pembrolizumab and showed a 2-fold or greater change from baseline in intratumoral CD3+ lymphocytic infiltration is presented. Evaluations were based on pathologist score.

Time frame:
Baseline and Week 7
Reported as:
Count of participants · Participants
Number of Participants Treated With Neoadjuvant Pembrolizumab With a 2-fold or Greater Change From Baseline in Intratumoral CD3+ Lymphocytic Infiltration
ParticipantsNeoadjuvant Pembrolizumab + RCC Resection
Number of Participants Treated With Neoadjuvant Pembrolizumab With a 2-fold or Greater Change From Baseline in Intratumoral CD3+ Lymphocytic Infiltration1
SecondaryChange From Baseline in Levels of Gene Expression of Immune Modulatory Receptors in Tumors of Participants Treated With Neoadjuvant Pembrolizumab

The change from baseline in levels of gene expression of immune modulatory receptors in tumors of participants treated with neoadjuvant pembrolizumab was presented.

Time frame:
Baseline and Week 7

No measurements were reported for this outcome.

SecondaryChange From Baseline in Number of T Cells in Tumors of Participants Treated With Neoadjuvant Pembrolizumab

The change from baseline in number of T cells in tumors of participants treated with neoadjuvant pembrolizumab was presented.

Time frame:
Baseline and Week 7

No measurements were reported for this outcome.

SecondaryChange From Baseline in Number of Activated T Cells in Peripheral Blood of Participants Treated With Neoadjuvant Pembrolizumab

The change from baseline in the number of activated T cells in peripheral blood of participants treated with neoadjuvant pembrolizumab was presented.

Time frame:
Baseline and Week 7

No measurements were reported for this outcome.

SecondaryChange From Baseline in Levels of Programmed Cell Death 1 Ligand 1 (PD-L1) Protein in Tumors of Participants Treated With Neoadjuvant Pembrolizumab

The change from baseline in levels of programmed cell death 1 ligand 1 (PD-L1) protein in tumors of participants treated with neoadjuvant pembrolizumab in participants who received neoadjuvant pembrolizumab was presented.

Time frame:
Baseline and Week 7

No measurements were reported for this outcome.

SecondaryChange From Baseline in Levels of Programmed Cell Death 1 Ligand 2 (PD-L2) Protein in Tumors of Participants Treated With Neoadjuvant Pembrolizumab

The change from baseline in levels of programmed cell death 1 ligand 2 (PD-L2) protein in tumors of participants treated with neoadjuvant pembrolizumab in participants who received neoadjuvant pembrolizumab was presented.

Time frame:
Baseline and Week 7

No measurements were reported for this outcome.

PrimaryNumber of Participants Treated With Neoadjuvant Pembrolizumab With a 2-fold or Greater Change From Baseline in Intratumoral CD8+ Lymphocytic Infiltration

The number of participants who received neoadjuvant pembrolizumab and showed a 2-fold or greater change from baseline in intratumoral CD8+ lymphocytic infiltration is presented. Evaluations were based on pathologist score.

Time frame:
Baseline and Week 7
Reported as:
Count of participants · Participants
Number of Participants Treated With Neoadjuvant Pembrolizumab With a 2-fold or Greater Change From Baseline in Intratumoral CD8+ Lymphocytic Infiltration
ParticipantsNeoadjuvant Pembrolizumab + RCC Resection
Number of Participants Treated With Neoadjuvant Pembrolizumab With a 2-fold or Greater Change From Baseline in Intratumoral CD8+ Lymphocytic Infiltration1
PrimaryNumber of Participants Treated With Neoadjuvant Pembrolizumab With a 2-fold or Greater Change From Baseline in Intratumoral FoxP3+ Lymphocytic Infiltration

The number of participants who received neoadjuvant pembrolizumab and showed a 2-fold or greater change from baseline in intratumoral FoxP3+ (forkhead box protein P3 positive) lymphocytic infiltration is presented. Evaluations were based on pathologist score.

Time frame:
Baseline and Week 7
Reported as:
Count of participants · Participants
Number of Participants Treated With Neoadjuvant Pembrolizumab With a 2-fold or Greater Change From Baseline in Intratumoral FoxP3+ Lymphocytic Infiltration
ParticipantsNeoadjuvant Pembrolizumab + RCC Resection
Number of Participants Treated With Neoadjuvant Pembrolizumab With a 2-fold or Greater Change From Baseline in Intratumoral FoxP3+ Lymphocytic Infiltration0

Adverse events

Collected over Up to 77 weeks. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Neoadjuvant Pembrolizumab + RCC Resection0/6 (0%)1/4 (25%)4/4 (100%)
Neoadjuvant Pembrolizumab+Resection+Post-Surgery Pembrolizumab0/1 (0%)1/1 (100%)1/1 (100%)
SOC RCC Resection1/4 (25%)0/3 (0%)0/3 (0%)
RCC Resection + Post-Resection Pembrolizumab0/1 (0%)0/1 (0%)1/1 (100%)
Most frequent serious events
Most frequent serious events
EventNeoadjuvant Pembrolizumab + RCC ResectionNeoadjuvant Pembrolizumab+Resection+Post-Surgery PembrolizumabSOC RCC ResectionRCC Resection + Post-Resection Pembrolizumab
Metabolism and nutrition disordersMetabolism and nutrition disorders0/41/10/30/1
Infections and infestationsInfections and infestations1/40/10/30/1
Most frequent other events
Showing 10 of 13
Most frequent other events
EventNeoadjuvant Pembrolizumab + RCC ResectionNeoadjuvant Pembrolizumab+Resection+Post-Surgery PembrolizumabSOC RCC ResectionRCC Resection + Post-Resection Pembrolizumab
General disorders and administration site conditionsGeneral disorders0/41/10/30/1
General disorders and administration site conditionsGeneral disorders0/40/10/31/1
InvestigationsInvestigations0/40/10/31/1
Metabolism and nutrition disordersMetabolism and nutrition disorders0/41/10/30/1
Musculoskeletal and connective tissue disordersMusculoskeletal and connective tissue disorders0/40/10/31/1
Skin and subcutaneous tissue disordersSkin and subcutaneous tissue disorders0/41/10/30/1
Skin and subcutaneous tissue disordersSkin and subcutaneous tissue disorders1/41/10/31/1
Eye disordersEye disorders1/40/10/30/1
General disorders and administration site conditionsGeneral disorders1/40/10/30/1
General disorders and administration site conditionsGeneral disorders1/40/10/30/1

Baseline characteristics

Age, Continuous
Age, Continuous(Years)Neoadjuvant Pembrolizumab + RCC ResectionRCC ResectionTotal
Mean66.5 ± 5.255.3 ± 9.162.0 ± 8.8
Sex: Female, Male
Sex: Female, Male(Participants)Neoadjuvant Pembrolizumab + RCC ResectionRCC ResectionTotal
Female123
Male527
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Neoadjuvant Pembrolizumab + RCC ResectionRCC ResectionTotal
Hispanic or Latino000
Not Hispanic or Latino6410
Unknown or Not Reported000
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Neoadjuvant Pembrolizumab + RCC ResectionRCC ResectionTotal
American Indian or Alaska Native000
Asian123
Native Hawaiian or Other Pacific Islander000
Black or African American000
White527
More than one race000
Unknown or Not Reported000
08

Study locations

No study locations are listed for this record.

09

References and documents

Study documents

  • Protocol and statistical analysis plan · Sep 13, 2018

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

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jul 16, 2020, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT02212730
Lead sponsor
Merck Sharp & Dohme LLC
Responsible party
Sponsor
First posted
Aug 8, 2014
Start date
Dec 3, 2014
Primary completion
Jul 5, 2019
Completion
Jul 5, 2019
Results posted
Jul 16, 2020
Last update
Jul 16, 2020

Study contacts

Medical Director
study director · Merck Sharp & Dohme LLC

Oversight

Data monitoring committee
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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