Phase 3
N=994
Safety and Efficacy Study of Pembrolizumab (MK-3475) as Monotherapy in the Adjuvant Treatment of Renal Cell Carcinoma Post Nephrectomy (MK-3475-564/KEYNOTE-564)
Renal Cell Carcinoma
Bottom Line
View on ClinicalTrials.gov: NCT03142334 ↗Enrolled (actual)
994
Serious AEs
15.9%
Results posted
Dec 2021
Primary outcome: Primary: Disease-free Survival (DFS) as Assessed by the Investigator — NA; NA Months — p=0.0010
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Pembrolizumab (Biological); Placebo (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Merck Sharp & Dohme LLC
- Primary completion
- Dec 2020
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Disease-free Survival (DFS) as Assessed by the Investigator |
NA; NA | 0.0010 sig |
| SECONDARY Overall Survival (OS) |
— | — |
| SECONDARY Number of Participants Who Experienced an Adverse Event (AE) |
— | — |
| SECONDARY Number of Participants Who Discontinued Study Drug Due to an AE |
— | — |
| SECONDARY First Local Disease Recurrence-specific Survival (DRSS1) as Assessed by the Investigator |
— | — |
| SECONDARY Second Disease Recurrence-Specific Survival (DRSS2) as Assessed by the Investigator |
— | — |
| SECONDARY Event-Free Survival (EFS) as Assessed by the Blinded Independent Central Review (BICR) |
— | — |
| SECONDARY DFS According to Participant Programmed Cell Death-Ligand 1 (PD-L1) Expression Status (Positive, Negative) as Assessed by the Investigator |
— | — |
| SECONDARY OS According to Participant PD-L1 Expression Status (Positive, Negative) |
— | — |
| SECONDARY Change From Baseline in the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30) Total Score |
— | — |
| SECONDARY Change From Baseline in the Functional Assessment of Cancer Therapy Kidney Symptom Index-Disease Related Symptoms (FKSI-DRS) Index Score |
— | — |
Summary
The purpose of this study is to evaluate the safety and efficacy of pembrolizumab (MK-3475) in the adjuvant treatment of adult participants who have undergone nephrectomy and have intermediate-high risk, high risk, or M1 no evidence of disease (M1 NED) renal cell carcinoma (RCC) with clear cell component.
The primary study hypothesis is that pembrolizumab is superior to placebo with respect to Disease-free Survival (DFS) as assessed by the Investigator in male and female participants with intermediate-high risk, high risk and M1 NED RCC.
Eligibility Criteria
Inclusion Criteria
- Has histologically confirmed diagnosis of renal cell carcinoma (RCC) with clear cell component with or without sarcomatoid features
- 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 treatment
- Male participants of childbearing potential must agree to use an adequate method of contraception, starting with the first dose of study treatment through 120 days after the last dose of study treatment
- Has intermediate-high risk, high risk, or M1 no evidence of disease (NED) RCC as defined by the following pathological tumor-node-metastasis and Fuhrman grading status:
- Intermediate-high risk RCC: pT2, Grade 4 or sarcomatoid, N0, M0; pT3, Any Grade, N0, M0
- High risk RCC: pT4, Any Grade N0, M0; pT Any stage, Any Grade, N+, M0
- M1 NED RCC participants who present not only with the primary kidney tumor but also solid, isolated, soft tissue metastases that can be completely resected at one of the following: the time of nephrectomy (synchronous) or, ≤1 year from nephrectomy (metachronous)
- Has received no prior systemic therapy for advanced RCC
- Has undergone a partial nephroprotective or radical complete nephrectomy (and complete resection of solid, isolated, soft tissue metastatic lesion(s) in M1 NED participants) with negative surgical margins
- Must have undergone a nephrectomy and/or metastasectomy ≥28 days prior to signing informed consent and ≤12 weeks prior to randomization
- Must be tumor-free as assessed by the Investigator and validated by either computed tomography (CT) or magnetic resonance imaging (MRI) scan of the brain and chest, abdomen, and pelvis and a bone scan ≤28 days from randomization
- Must have provided adequate tissue per the following: Nephrectomy only: tissue from nephrectomy (required); Synchronous M1 NED: tissue from nephrectomy (required) AND, metastasectomy tissue (if available); Metachronous M1 NED: tissue from metastasectomy (required) AND, nephrectomy tissue (if available)
- Has an Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of 0 or 1
- Has adequate organ function
Exclusion Criteria
- Has had major surgery, other than nephrectomy and/or resection of pre-existing metastases for M1 NED participants, within 12 weeks prior to randomization
- Has received prior radiotherapy for RCC
- Has pre-existing brain or bone metastatic lesions
- Has residual thrombus post nephrectomy in the vena renalis or vena cava
- Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study treatment
- Has an active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy is allowed
- Has a known additional malignancy that is progressing or required active treatment ≤3 years ago. Exceptions include early-stage cancers (carcinoma in situ or Stage 1) treated with curative intent, basal cell carcinoma of the skin, squamous cell carcinoma of the skin, in situ cervical cancer, in situ prostate cancer, or in situ breast cancer that has undergone potentially curative therapy
- Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis
- Has an active infection requiring systemic therapy
- Has a history of, or is currently on, dialysis
- Has a known history of human immunodeficiency virus (HIV) infection
- Has known active hepatitis B or hepatitis C virus infection
- Has a known history of active tuberculosis (Bacillus tuberculosis)
- Has had a prior solid organ transplant
- Has severe hypersensitivity (≥ Grade 3) to pembrolizumab and/or any of its excipients
- Is pregnant or breastfeeding, or expecting to conceive or f
Data sourced from ClinicalTrials.gov (NCT03142334). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.