Advanced Kidney Cancer MedDRA version: 20.1 Level: LLT Classification code 10023400 Term: Kidney cancer System Organ Class: 100000004864
Conditions
Interventions
Sponsors
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: -- Be > or = 18 years of age on day of signing informed consent - Have histologically confirmed diagnosis of RCC with clear cell component with or without sarcomatoid features - Have locally advanced/metastatic disease, i.e., newly diagnosed Stage IV RCC per American Joint Committee on Cancer or have recurrent disease. - Have measurable disease per RECIST 1.1 as assessed by the investigator /site radiologist. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions - Have received no prior systemic therapy for advanced RCC - Provide tumor tissue for biomarker analysis - Demonstrate adequate organ function 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 400 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 440
Exclusion criteria
Exclusion criteria: - Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to randomization - Has had major surgery within 4 weeks, received radiation therapy within 2 weeks prior to randomization, or has not recovered (i.e., = Grade 1 or at baseline) from AEs due to prior treatment. - Has had prior treatment with any anti-PD-1, or PD-L1, or PD-L2 agent or an antibody targeting any other immune-regulatory receptors or mechanisms. Examples of such antibodies include (but are not limited to) antibodies against IDO, PD-L1, IL-2R, and GITR - Has received prior systemic anti-cancer therapy for RCC (e.g., VEGF/VEGFR, chemotherapy or mTOR-targeting agents). - Has a diagnosis of immunodeficiency OR is receiving a systemic steroid therapy exceeding physiologic corticosteroid dose or any other form of immunosuppressive therapy within 7 days prior to randomization - Has an active autoimmune disease requiring systemic treatment within the past 2 years (i.e., with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs) OR with a documented history of clinically severe autoimmune disease - Has a known additional malignancy that has progressed or has required active treatment in the last 3 years - Has known active CNS metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are radiologically stable - Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis - Has a clinically significant gastrointestinal (GI) abnormality including: a) Malabsorption, total gastric resection, or any other condition that might affect the absorption of orally taken medication. b) Active GI bleeding, as evidenced by hematemesis, hematochezia or melena in the past 3 months without evidence of resolution documented by endoscopy or colonoscopy c) Intraluminal metastatic lesion with suspected bleeding, inflammatory bowel disease, ulcerative colitis or other GI condition associated with increased risk of perforation - Has QT interval corrected for heart rate (QTc) > or = 480 msec - Has a history of any of the following cardiovascular conditions within 12 months of randomization: Myocardial infarction, Unstable angina pectoris, Cardiac angioplasty or stenting, Coronary/peripheral artery bypass graft, Class III or IV congestive heart failure per New York Heart Association, Cerebrovascular accident or transient ischemic attack - Has a history of deep vein thrombosis or pulmonary embolism within 6 months of screening - Has poorly controlled hypertension defined as systolic blood pressure (SBP) > or = 150 mm Hg and/or diastolic blood pressure (DBP) > or = 90 mm Hg - Has evidence of inadequate wound healing - Has active bleeding disorder or other history of significant bleeding episodes within 30 days of randomization - Has hemoptysis within 6 weeks prior to randomization - Has current use (within 7 days of randomization) or anticipated need for treatment with drugs or foods that are known strong cytochrome P450 (CYP3A4/5) inhibitors - Has current use (within 7 days of randomization) or anticipated need for treatment with drugs that are known strong CYP3A4/5 inducers, including but not limited to carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, and St. John's wort; or drugs that are known with proarrhythmic potential - Has had a prior solid organ transplant
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1. To evaluate and compare PFS per RECIST 1.1 as assessed by BICR in subjects. treated with pembrolizumab plus axitinib versus sunitinib monotherapy. 2. To evaluate and compare OS in subjects treated with pembrolizumab plus axitinib versus sunitinib monotherapy.;Secondary Objective: 1. To compare ORR and DCR per RECIST 1.1 as assessed by BICR in subjects treated with a combination of pembrolizumab plus axitinib versus sunitinib monotherapy. DOR will also be evaluated. 2. To evaluate PFS rate per RECIST 1.1 as assessed by BICR at 12, 18, and 24 months based on data adequacy; to evaluate OS rates at 12, 18, and 24 months based on data adequacy. 3. To evaluate and compare safety and tolerability profiles in subjects treated with pembrolizumab plus axitinib versus sunitinib monotherapy. 4. To compare time to deterioration (TTD) based on the Functional Assessment of Cancer Therapy Kidney Symptom Index—Disease-Related Symptoms (FKSI-DRS) scale in subjects treated with pembrolizumab plus axitinib versus sunitinib monotherapy. 5. To assess the longitudinal score changes from baseline to 42 weeks as measured by European Organization for the Research and Treatment of Cancer (EORTC) QLQ-C30 global health status/quality of life scale.;Primary end point(s): - Progression Free Survival (PFS) per RECIST 1.1 as assessed by BICR - Overall Survival (OS);Timepoint(s) of evaluation of this end point: First Interim Analysis (IA1) Performed after enrollment completion, once a 7-mo minimum follow up has been achieved and a minimum of 305 PFS events have accrued. Expected to be 22 mo after the first sbj randomized. Approximately 48% of final required OS events (or 195 deaths) are expected at that time. Purpose: First IA for PFS and OS. Second Interim Analysis (IA2) Performed when approximately 74% of the final required OS events (or 299 deaths) have accrued, expected to be 31 mo after study start. At IA2, approximately 487 PFS events are expected. Purpose: Final analysis | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): •Objective Response Rate (ORR) – RECIST 1.1 by BICR Objective response rate is defined as the proportion of the subjects in the analysis population who have a CR or PR per RECIST 1.1. •Duration of Response (DOR) - RECIST 1.1 by BICR For subjects who demonstrate CR or PR, DOR is defined as the time from first documented evidence of CR or PR per RECIST 1.1 until disease progression per RECIST 1.1 or death due to any cause, whichever occurs first. See Section 8.6.1 for the censoring rules. •Disease Control Rate (DCR) - RECIST 1.1 by BICR Disease control rate is defined as the percentage of subjects who have achieved CR, PR, SD of = 6 months based on assessments by BICR per RECIST 1.1. •Safety endpoints: The following safety parameters will be analyzed: AEs and SAEs graded per NCI CTCAE, Version 4.0 criteria with time to onset/recovery, causality and outcome; changes in laboratory values, vital signs since baseline, treatment discontinuations and reason for discontinuation, death and cause of death, etc. Concomitant medications will be collected with time and reasons for use. •Health-Related Quality of Life Endpoints: FKSI-DRS, EORTC-QLQ-C30, and EuroQol EQ-5D-3L questionnaires. As of end of January 2020, PRO data will no longer be collected.;Timepoint(s) of evaluation of this end point: Imaging after randomization will be performed at Week 12 (84 days ±7 days), then Q6W (42 days ±7 days) through Week 54, then Q12W (84 days ±7 days) thereafter until PD is BICR verified or further confirmed by the investigator. Imaging visit window may be ± 14 days after Week 104. Unscheduled imaging can be performed as clinically indicated. The timing of imaging assessments should follow calendar days from randomization and should not be adjusted for dose delays or cycle starts. Safety and Health-Related Quality of Life assessments are cycle based. The DMC has responsibility for assessment of overall risk: benefit. The DMC will review safety periodically (every | — |
Countries
Brazil, Canada, Czechia, Czech Republic, France, Germany, Hungary, Ireland, Japan, Korea, Republic of, Poland, Russian Federation, Spain, Taiwan, Ukraine, United Kingdom, United States
Contacts
Public ContactGlobal Clinical Trial Operations
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
Outcome results
None listed