Treatment of participants with RCC in the adjuvant setting MedDRA version: 21.0 Level: LLT Classification code 10038395 Term: Renal carcinoma System Organ Class: 100000004864
Conditions
Interventions
Product Name: Pembrolizumab
Product Code: MK-3475
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: PEMBROLIZUMAB
CAS Number: 1374853-91-4
Current Sponsor code: MK-3475
Other descriptive
Sponsors
Merck Sharp & Dohme Corp.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Must have histologically confirmed diagnosis of RCC with clear cell component with or without sarcomatoid features. Diagnosis of RCC with clear cell component is to be made by the investigator and does not require central histology review 2.Be = 18 years of age on day of signing informed consent 3.Female participants of childbearing potential must have a negative urine or serum pregnancy test within 72 hours prior to randomization. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required 4.Female participants of childbearing potential must be willing to use an adequate method of contraception as outlined in the protocol, for the course of the trial through 120 days after the last dose of trial drug 5.Male participants of childbearing potential must be willing to use an adequate method of contraception as outlined in the protocol, for the course of the trial through 120 days after the last dose of trial drug 6.The participant provides written informed consent/assent for the trial. The participant may also provide consent/assent for Future Biomedical Research; however the participant may participate in the main trial without participating in Future Biomedical Research 7.Have intermediate-high risk, high risk, or M1 NED RCC as defined by the following pathological tumor-node-metastasis and Fuhrman grading status: a)Intermediate-high risk RCC -pT2, Gr. 4 or sarcomatoid, N0, M0 -pT3, Any Gr., N0, M0 b)High risk RCC - pT4, Any Gr. N0, M0 -pT Any stage, Any Gr., N+, M0 c)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) 8.Have received no prior systemic therapy for advanced RCC 9.Have 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 10.Must have undergone a nephrectomy and/or metastasectomy =28 days prior to signing informed consent and =12 weeks prior to randomization. 11.Must be tumor-free as assessed by the Investigator and validated by either CT or MRI scan of the brain and CAP and a bone scan =28 days from randomization. All baseline scans must be sent to the central imaging vendor and receipt must be confirmed prior to randomization 12.Must have provided adequate tissue per the following: - Nephrectomy only: tissue from nephrectomy (required). - Synchronous M1 NED: tissue from nephrectomy (required) AND, metastasectomy issue (if available). - Metachronous M1 NED: tissue from metastasectomy (required) AND, nephrectomy tissue (if available). Adequacy of the samples for biomarker analysis will be evaluated by a central laboratory. 13.Have an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1 14.Have adequate organ function as defined in the protocol. Specimens must be collected within 10 days prior to randomization Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 475 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 475
Exclusion criteria
Exclusion criteria: 1.Has had major surgery, other than nephrectomy and/or resection of pre-existing metastases for M1 NED participants, within 12 weeks prior to randomization 2.Has received prior radiotherapy for RCC 3. Has pre-existing brain or bone metastatic lesions. 4.Has residual thrombus post nephrectomy in the vena renalis or vena cava 5.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 6.Has an active autoimmune disease that has required systemic treatment in past 2 years (ie, with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed 7.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 8.Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis 9.Has an active infection requiring systemic therapy 10. Has a history of, or is currently on, dialysis 11.Has a known history of human immunodeficiency virus infection. No human immunodeficiency virus testing is required unless mandated by local health authority 12.Has a known active hepatitis B (hepatitis B surface antigen reactive) or hepatitis C virus (eg, hepatitis C virus [HCV] RNA [qualitative] is detected) 13.Has a known history of active tuberculosis (Bacillus tuberculosis) 14.Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the participant’s participation for the full duration of the trial, or is not in the best interest of the participant to participate, in the opinion of the treating investigator 15.Has a known psychiatric or substance abuse disorder that would interfere with the cooperation with the requirements of the trial in the opinion of the investigator 16.Has had a prior solid organ transplant 17.Has severe hypersensitivity (=Grade 3) to pembrolizumab and/or any of its excipients 18.A woman of childbearing potential (WOCBP) who has a positive urine pregnancy test within 72 hours before randomization. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. Participants must be excluded/discontinued from the trial in the event of a positive or borderline positive test result 19.Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the Screening visit through 120 days after the last dose of study treatment 20.Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another co-inhibitory T-cell receptor (ie, CTLA-4, OX-40, CD137) or has previously participated in a Merck pembrolizumab (MK 3475) clinical trial 21.Has received prior anticancer therapy, monoclonal antibody, chemotherapy, or an investigational agent or device within 4 weeks
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare disease-free survival (DFS) as assessed by the investigator for participants treated with pembrolizumab versus those receiving placebo ;Secondary Objective: 1. To compare a. overall survival (OS) for participants treated with pembrolizumab versus those receiving placebo b. the safety and tolerability profiles for participants treated with pembrolizumab versus those receiving placebo c. measures of disease recurrence-specific survival (DRSS), as assessed by the investigator, in participants treated with pembrolizumab versus those receiving placebo d. event-free survival (EFS) as assessed by the blinded independent radiology review for participants treated with pembrolizumab vs those receiving placebos e. DFS and OS according to participants’ PD-L1 expression status (Positive, Negative) for participants treated with pembrolizumab versus those receiving placebo 2. To evaluate patient-reported outcomes (PROs) with the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC-QLQ- C30) and the Functional Assessment of Cancer Therapy Kidney Symptom Index – Disease Related Symptoms (FKSI-DRS);Primary end point(s): Disease-free survival (DFS) as assessed by the investigator;Timepoint(s) of evaluation of this end point: • First Interim Analysis (IA1) Interim analysis for DFS Timing: When at least 265 disease recurrence events by investigator assessment have accrued and a minimum follow-up (time from last participant randomized to IA1) of 12 months is achieved. • Second Interim Analysis (IA2) Final analysis for DFS Timing: Final analysis of DFS when approximately 332 DFS events by investigator assessment have accrued if DFS is not rejected at IA1 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Overall survival (OS). ;Timepoint(s) of evaluation of this end point: • First Interim Analysis (IA1) Interim analysis for OS. Timing: When at least 265 disease recurrence events by investigator assessment have accrued and a minimum follow-up (time from last participant randomized to IA1) of 12 months is achieved. Approximately 94 OS events are expected at this time. • Second Interim Analysis (IA2) Interim analysis for OS Timing: when approximately 332 DFS events by investigator assessment have accrued if DFS is not rejected at IA1. Approximately 132 OS events are expected at this time. • Third Interim Analysis (IA3) Interim analysis for OS Timing: When approximately 172 OS events have accrued, • Final analysis (FA) Final analysis for OS Timing: When approximately 200 OS events have accrued | — |
Countries
Argentina, Australia, Brazil, Canada, Chile, China, Colombia, Czech Republic, Finland, France, Germany, Ireland, Italy, Japan, Korea, Republic of, Netherlands, New Zealand, Poland, Russian Federation, Spain, Taiwan, United Kingdom, United States
Contacts
Public ContactGlobal Clinical Trial Operations
Merck Sharp & Dohme Corp.
Outcome results
None listed