Renal Cell Carcinoma MedDRA version: 26.0 Level: LLT Classification code 10038409 Term: Renal cell carcinoma NOS System Organ Class: 100000004864
Conditions
Interventions
Trade Name: KEYTRUDA (pembrolizumab, MK-3475)
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Pembrolizumab
CAS Number: 1374853-91-4
Current Sponsor code: MK-3475
Concentration unit: m
Sponsors
Merck Sharp & Dohme LLC
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Has a histologically confirmed diagnosis of locally advanced/metastatic ccRCC (with or without sarcomatoid features), ie, Stage IV RCC per AJCC 2. Has received no prior systemic therapy for advanced RCC. [1L participants] 3. Has measurable disease per RECIST 1.1 as assessed by BICR. Lesions situated in a previously irradiated area are considered measurable if progression has been shown in such lesions 4. Has a KPS =70% assessed =10 days before randomization/allocation. 5. Is able to swallow oral medication 6. Submits an archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated. FFPE tissue blocks are preferred to slides. Newly obtained biopsies are preferred to archived tissue 7. Has adequate organ function. Specimens must be collected within 10 days before the start of study intervention 8. Participants receiving bone resorptive therapy (including but not limited to bisphosphonate or RANK-L inhibitor) must have therapy initiated at least 2 weeks before randomization/allocation 9. Has adequately controlled BP with or without antihypertensive medications, defined as BP =150/90 mm Hg with no change in antihypertensive medications within 1 week before randomization/allocation 10. Is male or female, from 18 years to 120 years of age inclusive, at the time of signing the informed consent 11. Male participants are eligible to participate if they agree to the following during the intervention period and for at least the time needed to eliminate each study intervention after the last dose of study intervention. The length of time required to continue contraception for each study intervention is as follows: - Lenvatinib, belzutifan – 7 days - Pembrolizumab, MK-1308A, MK-4280A, MK-7684A– no male contraception measures are required - Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent OR - Must agree to use contraception unless confirmed to be azoospermic (vasectomized or secondary to medical cause) documented from the site personnel’s review of the participant’s medical records, medical examination, or medical history interview) as detailed below: - Agree to use a male condom plus partner use of an additional contraceptive method when having penile-vaginal intercourse with a WOCBP who is not currently pregnant - Contraceptive use by men should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies 12. A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies: - Is not a WOCBP OR - Is a WOCBP and : - uses a contraceptive method that is highly effective (with a failure rate of <1% per year), with low user dependency, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis), during the intervention period and for at least the time needed to eliminate each study intervention after the last dose of study intervention. The length of time required to continue contraception for each study intervention is as follows: - Lenvatinib, belzutifan – 30 days - Pembrolizumab, MK-1308A, MK-4280A, MK-7684A – 120 days The investigator should evaluate the potential for contraceptive method failure (ie, noncompliance, recently initiated) in relationship to the first dose of s
Exclusion criteria
Exclusion criteria: 1. Has clinically significant cardiavasculair disease, within 12 months from first dose of study intervention,including or New York Heart Association Class III or IV congestive heart failure, unstable angina, myocardial infarction, cerebral vascular accident, or cardiac arrhythmia associated with hemodynamic instability. 2. Prolongation of QTcF interval to >480 ms 3. Has a LVEF below the institutional (or local laboratory) normal range as determined by MUGA or ECHO 4. Has had major surgery within 3 weeks before first dose of study interventions 5. Has urine protein =1 g/24 hours 6. Has a history of interstitial lung disease, history of (non-infectious) pneumonitis that required steroids, or has current pneumonitis 7. Has symptomatic pleural effusion (for example cough, dyspnea, pleuritic chest pain). A participant who is clinically stable after treatment for these conditions (including therapeutic thoraco- or paracentesis) is eligible 8. Has a history of inflammatory bowel disease 9. Has preexisting =Grade 3 GI or non-GI fistula 10. Has malabsorption due to prior GI surgery or GI disease 11. Active hemoptysis (bright red blood of at least 0.5 teaspoon) within 3 weeks prior to the first dose of study intervention. 12. Has received prior radiotherapy within 2 weeks of start of study intervention or has radiation related toxicities requiring corticosteroids 13. Has received a live or live attenuated vaccine within 30 days before the first dose of study drug. 14. Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration. 15. Have been previously allocated/randomized to study intervention in any substudy of protocol MK-3475-U03 16. 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 drug 17. Has a known additional malignancy that is progressing or has required active treatment within the past 3 years 18. Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, (ie, without evidence of progression) for at least 4 weeks by repeat imaging, clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study intervention 19. Has radiographic evidence of encasement or invasion of a major blood vessel, or of intratumoral cavitation 20. Has a history of hypersensitivity reaction to any of the investigational agent(s) included in this study. For example, but not limited to: - Has a severe hypersensitivity (=Grade 3) to pembrolizumab and/or any of its excipients - Has a history of severe hypersensitivity reaction (eg, generalized rash/erythema, hypotension, bronchospasm, angioedema, or anaphylaxis) to lenvatinib 21. Has an active autoimmune disease that has required systemic treatment in the 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 22. Has an active infection requiring systemic therapy 23. Has a known history of HIV infection. No HIV testing is required unless mandated by local hea
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1. Safety Lead-in Phase: To assess the safety and tolerability, and to establish a recommended Phase 2 dose (RP2D) if applicable, of certain treatment combinations. 2. Efficacy Phase: To assess the safety and tolerability of each treatment arm based on the proportion of participants with adverse events (AEs) 3. Efficacy Phase: To evaluate objective response rate (ORR) of each treatment arm as assessed by Blinded Independent Central Review (BICR) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1);Secondary Objective: 1. Efficacy Phase: To evaluate the duration of response (DOR) as assessed by BICR per RECIST 1.1 2. Efficacy Phase: To evaluate progression-free survival (PFS) as assessed by BICR per RECIST 1.1 3. Efficacy Phase: To evaluate overall survival (OS) 4. Efficacy Phase: To evaluate clinical benefit rate (CBR) per RECIST 1.1 as assessed by BICR ;Primary end point(s): 1. Safety Lead-in Phase: Number of participants who experience one or more dose-limiting toxicities (DLTs) 2. Safety Lead-in Phase: Number of participants who experience one or more adverse events (AEs) 3. Safety Lead-in Phase: Number of participants who discontinue study treatment due to an AE 4. Efficacy Phase: Number of participants who experience one or more DLTs 5. Efficacy Phase: Number of participants who experience one or more AEs 6. Efficacy Phase: Number of participants who discontinue study treatment due to an AE 7. Efficacy Phase: Objective response rate (ORR);Timepoint(s) of evaluation of this end point: 1. Up to ~21 days 2. Up to ~21 days 3. Up to ~21 days 4. Up to ~21 days 5. Up to ~21 days 6. Up to ~43 months 7. Up to ~43 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Efficacy Phase: Duration of response (DOR) 2. Efficacy Phase: Progression-free survival (PFS) 3. Efficacy Phase: Overall survival (OS) 4. Efficacy Phase: Clinical benefit rate (CBR);Timepoint(s) of evaluation of this end point: 1. Up to ~43 months 2. Up to ~43 months 3. Up to ~43 months 4. Up to ~43 months | — |
Countries
Australia, Canada, Chile, Colombia, France, Hungary, Israel, Korea, Republic of, Mexico, Netherlands, New Zealand, Poland, Spain, United Kingdom, United States
Contacts
Public ContactGlobal Clinical Trials Operations
Merck Sharp & Dohme LLC
Outcome results
None listed