KEYMAKER-U01 Substudy 2: Efficacy and Safety Study of Pembrolizumab (MK-3475) When Used With Investigational Agents in Treatment-naïve Participants With Anti-programmed Cell Death Receptor Ligand 1 (PD-L1) Positive Advanced Non-small Cell Lung Cancer (NSCLC) (MK-3475-01B/KEYMAKER-U01B)
- Conditions
- Carcinoma, Non-Small-Cell Lung
- Interventions
- Registration Number
- NCT04165083
- Lead Sponsor
- Merck Sharp & Dohme LLC
- Brief Summary
The purpose of this study is to assess the efficacy and safety of pembrolizumab (MK-3475) in combination with MK-4830 in treatment-naïve participants with advanced squamous or non-squamous NSCLC that is PD-L1 positive.
This study is one of three pembrolizumab substudies being conducted under one pembrolizumab umbrella master protocol (MK-3475-U01/KEYMAKER-U01).
The pembrolizumab+ MK-0482 arm was added with Amendment 6.
- Detailed Description
The master screening protocol is MK-3475-U01(KEYMAKER-U01) - NCT04165798
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 120
Not provided
- Has a diagnosis of small cell lung cancer
- 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 before the first dose of study treatment
- Has a known additional malignancy that is progressing or has required active treatment within the past 2 years
- Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
- Has an active autoimmune disease that has required systemic treatment in the past 2 years
- Has a history of (noninfectious) pneumonitis that required steroids or has current pneumonitis
- Has an active infection requiring systemic therapy
- Has clinically significant cardiac disease, including unstable angina, acute myocardial infarction within 6 months from Day 1 of study treatment, or New York Heart Association Class III or IV congestive heart failure
- 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 known psychiatric or substance abuse disorders that would interfere with cooperating with the requirements of the study
- Has had major surgery <3 weeks before the first dose of study treatment
- Has received prior radiation therapy to the lung that is >30 Gray (Gy) within 6 months of the first dose of study treatment
- Has received any prior immunotherapy and was discontinued from that treatment due to a severe or worse immune-related adverse event (irAE)
- Has had chemotherapy or biological cancer therapy within 4 weeks before the first dose of study treatment or has not recovered to Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 or better from the AEs due to cancer therapeutics administered more than 4 weeks before the first dose of study treatment (including participants who had previous immunomodulatory therapy with residual irAEs)
- Has received a live vaccine within 30 days before the first dose of study treatment. Any licensed COVID-19 vaccine (including for Emergency Use) in a particular country is allowed as long as they are messenger ribonucleic acid (mRNA) vaccines, adenoviral vaccines, or inactivated vaccines. Investigational vaccines (ie, those not licensed or approved for Emergency Use) are not allowed
- Has received prior systemic cytotoxic chemotherapy or other targeted or biological antineoplastic therapy for metastatic disease.
- Has received prior therapy with an anti-programmed cell death receptor 1 (PD-1), anti-programmed cell death receptor ligand 1 (PD-L1), or anti-programmed cell death receptor ligand 2 (PD-L2) agent or prior therapy targeting other immuno-regulatory receptors or mechanisms
- Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks before the first dose of study treatment
- Has had a severe hypersensitivity reaction to treatment with monoclonal antibodies (including pembrolizumab) and/or any of their excipients
- 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
- Has had an allogenic tissue/solid organ transplant
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Pembrolizumab + MK-4830 Pembrolizumab On Day 1 of each 3-week cycle, participants receive pembrolizumab 200 mg intravenously (IV) PLUS MK-4830 IV for a maximum of 35 cycles (approximately 2 years) Pembrolizumab + MK-0482 Pembrolizumab On Day 1 of each 3-week cycle, participants receive pembrolizumab 200 mg intravenously (IV) PLUS MK-0482 IV for a maximum of 35 cycles (approximately 2 years) Pembrolizumab + MK-4830 MK-4830 On Day 1 of each 3-week cycle, participants receive pembrolizumab 200 mg intravenously (IV) PLUS MK-4830 IV for a maximum of 35 cycles (approximately 2 years) Pembrolizumab + MK-0482 MK-0482 On Day 1 of each 3-week cycle, participants receive pembrolizumab 200 mg intravenously (IV) PLUS MK-0482 IV for a maximum of 35 cycles (approximately 2 years)
- Primary Outcome Measures
Name Time Method Objective Response Rate (ORR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Up to approximately 24 months ORR was defined as the percentage of participants in the analysis population who had a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1.
- Secondary Outcome Measures
Name Time Method Number of Participants Who Experience One or More Adverse Events (AEs) Up to approximately 27 months An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment.
Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Up to approximately 24 months PFS is defined as the time from first dose of study treatment until either the earliest date of documented progressive disease (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD.
Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE) Up to approximately 24 months An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment.
Trial Locations
- Locations (39)
MedStar Franklin Square Medical Center ( Site 0033)
🇺🇸Baltimore, Maryland, United States
Abramson Cancer Center of the University of Pennsylvania ( Site 0010)
🇺🇸Philadelphia, Pennsylvania, United States
Massachusetts General Hospital ( Site 0003)
🇺🇸Boston, Massachusetts, United States
Dana Farber Cancer Institute ( Site 0002)
🇺🇸Boston, Massachusetts, United States
Cleveland Clinic ( Site 0006)
🇺🇸Cleveland, Ohio, United States
Shaare Zedek Medical Center ( Site 0075)
🇮🇱Jerusalem, Israel
City of Hope ( Site 0014)
🇺🇸Duarte, California, United States
Meir Medical Center ( Site 0071)
🇮🇱Kfar-Saba, Israel
Rambam Health Care Campus-Oncology ( Site 0076)
🇮🇱Haifa, Israel
Sanford Fargo Medical Center ( Site 0039)
🇺🇸Fargo, North Dakota, United States
Banner MD Anderson Cancer Center ( Site 0001)
🇺🇸Gilbert, Arizona, United States
UCSF Medical Center at Mission Bay ( Site 0007)
🇺🇸San Francisco, California, United States
Georgetown University ( Site 0036)
🇺🇸Washington, District of Columbia, United States
University of Kentucky Markey Cancer Center ( Site 0019)
🇺🇸Lexington, Kentucky, United States
Oncology Hematology West, PC DBA Nebraska Cancer Specialists ( Site 0031)
🇺🇸Omaha, Nebraska, United States
Laura and Isaac Perlmutter Cancer Center at NYU Langone Health ( Site 0034)
🇺🇸New York, New York, United States
John Theurer Cancer Center at Hackensack University Medical Center ( Site 0037)
🇺🇸Hackensack, New Jersey, United States
Dartmouth Hitchcock Medical Center ( Site 0016)
🇺🇸Lebanon, New Hampshire, United States
Ohio State University Comprehensive Cancer Center ( Site 0015)
🇺🇸Columbus, Ohio, United States
Sanford Cancer Center ( Site 0038)
🇺🇸Sioux Falls, South Dakota, United States
The University of Texas MD Anderson Cancer Center ( Site 0009)
🇺🇸Houston, Texas, United States
Orszagos Koranyi Pulmonologiai Intezet ( Site 0060)
🇭🇺Budapest, Hungary
Petz Aladar Megyei Oktato Korhaz ( Site 0062)
🇭🇺Gyor, Gyor-Moson-Sopron, Hungary
Jász-Nagykun-Szolnok Vármegyei Hetényi Géza Kórház ( Site 0061)
🇭🇺Szolnok, Jasz-Nagykun-Szolnok, Hungary
Soroka Medical Center ( Site 0072)
🇮🇱Beer-Sheva, Israel
Chaim Sheba Medical Center ( Site 0070)
🇮🇱Ramat Gan, Israel
Rabin Medical Center ( Site 0074)
🇮🇱Petah Tikva, Israel
Azienda Ospedaliera Universitaria Careggi ( Site 0173)
🇮🇹Florence, Firenze, Italy
Sourasky Medical Center ( Site 0077)
🇮🇱Tel Aviv, Israel
Policlinico Gemelli di Roma ( Site 0174)
🇮🇹Roma, Lazio, Italy
IRCCS Ospedale San Raffaele ( Site 0171)
🇮🇹Milano, Italy
Severance Hospital ( Site 0080)
🇰🇷Seoul, Korea, Republic of
Seoul National University Bundang Hospital ( Site 0081)
🇰🇷Seongnam-si, Kyonggi-do, Korea, Republic of
Uniwersyteckie Centrum Kliniczne-Early Clinical Trials Unit ( Site 0150)
🇵🇱Gdańsk, Pomorskie, Poland
Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - P-Klinika Nowotworow Pluca i Klatki Pier
🇵🇱Warszawa, Mazowieckie, Poland
Szpital Wojewódzki im. Mikoaja Kopernika w Koszalinie-Oddzial Dzienny Chemioterapii ( Site 0152)
🇵🇱Koszalin, Zachodniopomorskie, Poland
ICO L Hospitalet ( Site 0090)
🇪🇸Hospitalet de Llobregat, Barcelona, Spain
Hospital Universitario Quiron Madrid ( Site 0091)
🇪🇸Pozuelo de Alarcon, Madrid, Spain
Samsung Medical Center ( Site 0082)
🇰🇷Seoul, Korea, Republic of