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)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Merck Sharp & Dohme LLC

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

8 Jun 2017 → 4 Feb 2026

Decision date (initial)

2023-01-23

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Merck Sharp & Dohme LLC

External identifiers

EU CT number

2022-501251-81-00

EudraCT number

2016-004351-75

WHO UTN

U1111-1275-8289

ClinicalTrials.gov

NCT03142334

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Therapy

To compare DFS as assessed by the investigator for participants treated with pembrolizumab versus those receiving placebo

Secondary objectives 6

1. To compare OS for participants treated with pembrolizumab versus those receiving placebo
2. To compare the safety and tolerability profiles for participants treated with pembrolizumab versus those receiving placebo
3. To compare measures of DRSS, as assessed by the investigator, for participants treated with pembrolizumab versus those receiving placebo
4. To compare EFS as assessed by the blinded independent radiology review for participants treated with pembrolizumab versus those receiving placebo.
5. To compare DFS and OS according to participants’ PD-L1 expression status (Positive, Negative) for participants treated with pembrolizumab versus those receiving placebo.
6. To evaluate PROs with the EORTC-QLQ-C30 and the FKSI-DRS.

Conditions and MedDRA coding

Renal cell carcinoma

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. Has histologically confirmed diagnosis of renal cell carcinoma (RCC) with clear cell component with or without sarcomatoid features
2. 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
3. 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
4. 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: 1) Intermediate-high risk RCC: pT2, Grade 4 or sarcomatoid, N0, M0; pT3, Any Grade, N0, M0 2) High risk RCC: pT4, Any Grade N0, M0; pT Any stage, Any Grade, N+, M0 3) 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)
5. Has received no prior systemic therapy for advanced RCC
6. 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
7. Must have undergone a nephrectomy and/or metastasectomy ≥28 days prior to signing informed consent and ≤12 weeks prior to randomization
8. 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
9. 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)
10. Has an Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of 0 or 1
11. Has adequate organ function

Exclusion criteria 20

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 (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy 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 (HIV) infection
12. Has known active hepatitis B or hepatitis C virus infection
13. Has a known history of active tuberculosis (Bacillus tuberculosis)
14. Has had a prior solid organ transplant
15. Has severe hypersensitivity (≥ Grade 3) to pembrolizumab and/or any of its excipients
16. 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 treatment
17. Has received prior therapy with an anti-programmed cell death protein 1 (anti-PD-1), anti-programmed cell death-ligand 1 (anti-PD-L1), or anti-programmed cell death-ligand 2 (anti-PD-L2) agent or with an agent directed to another co-inhibitory T-cell receptor (i.e., cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], OX-40, CD137 [tumor necrosis factor receptor superfamily member 9 (TNFRSF9)]) or has previously participated in a Merck pembrolizumab (MK-3475) clinical trial
18. Has received prior anticancer therapy, monoclonal antibody, chemotherapy, or an investigational agent or device within 4 weeks or 5 half-lives (whichever is longer) before first dose of study treatment or not recovered (i.e., must be ≤ Grade 1 or at Baseline) from AEs due to previously administered agents
19. Has received a live vaccine within 30 days prior to the first dose of study treatment
20. 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 the first dose of study treatment

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Disease-free Survival (DFS) as Assessed by the Investigator

Secondary endpoints 10

1. Overall Survival (OS)
2. Number of Participants Who Experienced an Adverse Event (AE)
3. Number of Participants Who Discontinued Study Drug Due to an AE
4. First Local Disease Recurrence-specific Survival (DRSS1) as Assessed by the Investigator
5. Visceral Disease Recurrence-Specific Survival (DRSS2) as Assessed by the Investigator
6. Event-Free Survival (EFS) as Assessed by the Blinded Independent Central Review (BICR)
7. DFS According to Participant Programmed Cell Death-Ligand 1 (PD-L1) Expression Status (Positive, Negative) as Assessed by the Investigator
8. OS According to Participant PD-L1 Expression Status (Positive, Negative)
9. Change From Baseline in the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30) Total Score
10. Change From Baseline in the Functional Assessment of Cancer Therapy Kidney Symptom Index-Disease Related Symptoms (FKSI-DRS) Index Score

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Merck Sharp & Dohme LLC

Sponsor organisation

Merck Sharp & Dohme LLC

Address

126 East Lincoln Avenue

City

Rahway

Postcode

07065-4607

Country

United States

Scientific contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Priyanka Chablani

Public contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Priyanka Chablani

Third parties 6

Locations

9 EU/EEA countries · 66 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 52 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

18 submissions — initial application plus substantial / non-substantial modifications