Study of Pembrolizumab Given With Ipilimumab or Placebo in Participants With Untreated Metastatic Non-Small Cell Lung Cancer (NSCLC) (MK-3475-598/KEYNOTE-598)

• Register: ClinicalTrials.gov
• Last refreshed on: 9 October 2023
• Main ID: NCT03302234
• Date of registration: 26/09/2017
• Prospective Registration: Yes
• Primary sponsor: Merck Sharp & Dohme LLC
• Public title: Study of Pembrolizumab Given With Ipilimumab or Placebo in Participants With Untreated Metastatic Non-Small Cell Lung Cancer (NSCLC) (MK-3475-598/KEYNOTE-598)
• Scientific title: A Phase 3, Randomized, Double-Blind Study of Pembrolizumab Plus Ipilimumab vs Pembrolizumab Plus Placebo in Previously Untreated, Stage IV, Metastatic Non-small Cell Lung Cancer Subjects Whose Tumors Are PD-L1 Positive (TPS = 50%) (KEYNOTE-598)
• Date of first enrolment: December 14, 2017
• Target sample size: 568
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/ct2/show/NCT03302234
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 3

Countries of recruitment

Argentina, Australia, Brazil, Canada, Chile, Colombia, France, Germany, Hungary, Ireland, Italy, Korea, Republic of, Latvia, Mexico, Peru, Poland, Russian Federation, South Africa, Spain, Taiwan, Thailand, Turkey, Ukraine, United Kingdom, United States

Contacts

• Name: Medical Director
• Affiliation: Merck Sharp & Dohme LLC

Key inclusion & exclusion criteria

Inclusion Criteria:

- Has a histologically or cytologically confirmed diagnosis of Stage IV metastatic
non-small cell lung cancer (NSCLC) (American Joint Committee on Cancer version 8)

- Has measurable disease per Response Evaluation Criteria in Solid Tumors Version 1.1
(RECIST 1.1) as determined by investigator

- Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

- Has a life expectancy of at least 3 months

- Has provided archival tumor tissue sample or newly obtained core or excisional biopsy
of a tumor lesion not previously irradiated

- Female participants of childbearing potential must have a negative serum pregnancy
test within 72 hours prior to receiving the first dose of study therapy

- Female participants of reproductive potential must agree to use contraception starting
from the first dose of study medication, throughout the study period, and for up to
120 days after the last dose of study medication

Exclusion Criteria:

- Has received prior systemic chemotherapy/other targeted or biological antineoplastic
therapy treatment for their Stage IV metastatic NSCLC

- Has a tumor that harbors an epidermal growth factor receptor (EGFR)-sensitizing
(activating) mutation or an anaplastic lymphoma kinase (ALK) translocation

- Is currently participating in or has participated in a trial of an investigational
agent or has used an investigational device within 4 weeks prior to the first dose of
study therapy

- Has received prior therapy with an anti-Programmed Cell Death Receptor 1 (PD-1),
anti-Programmed Cell Death Receptor Ligand 1 (anti-PD-L1), or anti- Programmed Cell
Death Receptor Ligand 2 (PD-L2) agent or with an agent directed to another stimulatory
or co-inhibitory T-cell receptor (eg, cytotoxic T-lymphocyte-associated protein 4
[CTLA-4], OX-40, CD137)

- Has received prior radiotherapy within 2 weeks of start of study therapy or received
lung radiation therapy of >30 Gray (Gy) within 6 months of the first dose of study
therapy

- Has recovered from all radiation-related toxicities, does not require corticosteroids,
and has not had radiation pneumonitis

- Is receiving systemic steroid therapy =7 days prior to the first dose of study therapy
or receiving any other form of immunosuppressive medication

- Has a known additional malignancy that is progressing or has required active treatment
within the past 3 years with the exception of curatively treated basal cell carcinoma
of the skin, squamous cell carcinoma of the skin and/or curatively resected in situ
cancers

- Has known untreated central nervous system (CNS) metastases and/or carcinomatous
meningitis

- 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)

- Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
(i.e., doses exceeding 10 mg daily of prednisone equivalent) or any other form of
immunosuppressive therapy within 7 days prior the first dose of study therapy

- Has a history of (non-infectious) pneumonitis that required systemic steroids or
current pneumonitis/interstitial lung disease

- Has had an allogeneic tissue/solid organ transplant

- Has received a live vaccine within 30 days prior to the first dose of study therapy

- Has an active infection requiring systemic therapy

- Has a known history of human immunodeficiency virus (HIV) infection

- Has a known history of hepatitis B or known active hepatitis C virus infection

- Has a known history of active tuberculosis

- Has known psychiatric or substance abuse disorders that would interfere with
cooperating with the requirements of the trial

- Is a regular user of any illicit drugs or had a recent history of substance abuse

- Is pregnant or breast feeding or expecting to conceive starting from the first dose of
study medication, throughout the study period, and for up to 120 days after the last
dose of study medication

- Has severe hypersensitivity to pembrolizumab and/or any of its excipients and/or to
ipilimumab and/or any of its excipients

- Has a c-ros oncogene 1 (ROS1) mutation



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Carcinoma, Non-Small-Cell Lung

Intervention(s)

Biological: Ipilimumab

Biological: Pembrolizumab

Other: Placebo

Primary Outcome(s)

Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Based on Blinded Independent Central Review (BICR) [Time Frame: Up to approximately 32 months (through data cut-off date 01 Sep 2020)]

Overall Survival (OS) [Time Frame: Up to approximately 32 months (through data cut-off date: 01 Sep 2020)]

Secondary Outcome(s)

Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status/Quality of Life (Items 29 and 30) Scale Score to Week 18 [Time Frame: Baseline, Week 18]

Number of Participants Who Discontinued Study Treatment Due to an AE [Time Frame: Up to approximately 24 months]

Number of Participants Who Experienced an Adverse Event (AE) [Time Frame: Up to approximately 27 months]

Duration of Response (DOR) Per RECIST 1.1 Based on BICR [Time Frame: Up to approximately 32 months (data cut-off date 01 Sep 2020)]

Objective Response Rate (ORR) Per RECIST 1.1 Based on BICR [Time Frame: Up to approximately 32 months (data cut-off date 01 Sep 2020)]

Time to True Deterioration (TTD) in Cough, Pain in Chest, and Shortness of Breath [Time Frame: Up to approximately 32 months (data cut-off date 01 Sep 2020)]

Secondary ID(s)

3475-598

KEYNOTE-598

2016-004364-20

MK-3475-598

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 10/09/2021
• URL: https://clinicaltrials.gov/ct2/show/results/NCT03302234