Study of Pembrolizumab (MK-3475) Monotherapy in Locally Advanced/Metastatic Renal Cell Carcinoma (MK-3475-427/KEYNOTE-427)

NCT ID: NCT02853344

Last Updated: 2023-04-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 275 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-09-30
• Study Completion Date: 2022-04-01

Brief Summary

The purpose of this study is to assess the safety and efficacy of monotherapy pembrolizumab (MK-3475) in participants with renal cell carcinoma (RCC). There will be two cohorts in this study: Cohort A will consist of participants with clear cell (cc) RCC and Cohort B will consist of participants with non-clear cell (ncc) RCC.

Conditions

Renal Cell Carcinoma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cohort A: Clear Cell RCC

Participants with clear cell RCC receive pembrolizumab 200 mg intravenously (IV) every 3 weeks (Q3W) for up to 35 doses (approximately 24 months).

Group Type: EXPERIMENTAL

Pembrolizumab

Intervention Type: BIOLOGICAL

IV infusion

Cohort B: Non-clear Cell RCC

Participants with non-clear cell RCC receive pembrolizumab 200 mg IV Q3W for up to 35 doses (approximately 24 months).

Group Type: EXPERIMENTAL

Pembrolizumab

Intervention Type: BIOLOGICAL

IV infusion

Interventions

Pembrolizumab

IV infusion

Intervention Type: BIOLOGICAL

Other Intervention Names

MK-3475; KEYTRUDA®

Eligibility Criteria

Inclusion Criteria

• Cohort A (clear cell RCC cohort) participant must have histologically confirmed diagnosis of clear cell RCC or RCC with clear cell component (with or without sarcomatoid features).
• Cohort B (non-clear cell RCC cohort) participant must have histologically confirmed diagnosis of non-clear cell RCC (with or without sarcomatoid features). Participants with tumors that have a component of clear cell histology are not eligible for inclusion in Cohort B.
• Has locally advanced/metastatic disease, i.e., newly diagnosed Stage IV RCC per American Joint Committee on Cancer (AJCC) or have recurrent disease.
• Has measurable disease per RECIST 1.1 as assessed by BICR.
• Has received no prior systemic therapy for advanced RCC. Prior neoadjuvant/adjuvant therapy for RCC is acceptable if completed >12 months prior to allocation.
• Must provide adequate tissue for biomarker analysis for Cohorts A and B from an archival tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated.
• Participants receiving bone resorptive therapy (including but not limited to bisphosphonate or RANK-L inhibitor) must have therapy initiated at least 2 weeks prior to treatment allocation.
• Has Karnofsky Performance Status (KPS) ≥70%, as assessed within 10 days prior to treatment allocation.
• Demonstrates adequate organ function.
• 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 drug.
• Male participants of childbearing potential must agree to use an adequate method of contraception starting with the first dose of study drug through 120 days after the last dose of study drug.

Exclusion Criteria

• Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks prior to allocation, has had major surgery within 4 weeks or radiation therapy within 2 weeks prior to allocation, or who has not recovered (i.e., ≤ Grade 1 or to Baseline) from AEs due to prior treatment.
• Had prior treatment with any anti-programmed cell death 1 (anti-PD-1), or anti-programmed cell death ligand 1 (PD-L1), or PD-L2 agent or an antibody targeting any other immune-regulatory receptors or mechanisms. Examples of such antibodies include antibodies against indoleamine-2,3-dioxygenase (IDO), PD-L1, interleukin 2 receptors (IL-2R), glucocorticoid-induced tumor necrosis factor receptor-related protein (GITR).
• Has a diagnosis of immunodeficiency OR is receiving a systemic steroid therapy exceeding 10 mg daily dose of prednisone or equivalent or any other form of immunosuppressive therapy within 7 days prior to allocation, except in the case of central nervous system (CNS) metastases (see below).
• Has an active autoimmune disease requiring systemic treatment within the past 2 years OR a documented history of clinically severe autoimmune disease.
• Has a known additional malignancy that has had progression or has required active treatment in the last 3 years. Note: Basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ, such as breast cancer in situ, that has undergone potentially curative therapy are acceptable.
• Has known active CNS metastases and/or carcinomatous meningitis.
• Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis.
• Has an active infection requiring systemic therapy.
• Has a known history of Human Immunodeficiency Virus (HIV) infection.
• Has known history of Hepatitis B or known active Hepatitis C.
• Has received a live virus vaccine within 30 days of allocation.
• Has had a prior solid organ transplant.
• Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of study drug.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

References

McDermott DF, Lee JL, Bjarnason GA, Larkin JMG, Gafanov RA, Kochenderfer MD, Jensen NV, Donskov F, Malik J, Poprach A, Tykodi SS, Alonso-Gordoa T, Cho DC, Geertsen PF, Climent Duran MA, DiSimone C, Silverman RK, Perini RF, Schloss C, Atkins MB. Open-Label, Single-Arm Phase II Study of Pembrolizumab Monotherapy as First-Line Therapy in Patients With Advanced Clear Cell Renal Cell Carcinoma. J Clin Oncol. 2021 Mar 20;39(9):1020-1028. doi: 10.1200/JCO.20.02363. Epub 2021 Feb 2.

Reference Type: RESULT

PMID: 33529051 (View on PubMed)

Topp BG, Channavazzala M, Mayawala K, De Alwis DP, Rubin E, Snyder A, Wolchok JD, Ribas A. Tumor dynamics in patients with solid tumors treated with pembrolizumab beyond disease progression. Cancer Cell. 2023 Sep 11;41(9):1680-1688.e2. doi: 10.1016/j.ccell.2023.08.004.

Reference Type: DERIVED

PMID: 37699333 (View on PubMed)

McDermott DF, Lee JL, Ziobro M, Suarez C, Langiewicz P, Matveev VB, Wiechno P, Gafanov RA, Tomczak P, Pouliot F, Donskov F, Alekseev BY, Shin SJ, Bjarnason GA, Castellano D, Silverman RK, Perini RF, Schloss C, Atkins MB. Open-Label, Single-Arm, Phase II Study of Pembrolizumab Monotherapy as First-Line Therapy in Patients With Advanced Non-Clear Cell Renal Cell Carcinoma. J Clin Oncol. 2021 Mar 20;39(9):1029-1039. doi: 10.1200/JCO.20.02365. Epub 2021 Feb 2.

Reference Type: DERIVED

PMID: 33529058 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

http://merckoncologyclinicaltrials.com

Merck Oncology Clinical Trials Information

Other Identifiers

MK-3475-427

Identifier Type: OTHER

Identifier Source: secondary_id

2016-000589-47

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

3475-427

Identifier Type: -

Identifier Source: org_study_id