KEYMAKER-U01 Substudy 3: Efficacy and Safety Study of Pembrolizumab (MK-3475) When Used With Investigational Agents in Participants With Advanced Non-small Cell Lung Cancer (NSCLC), Previously Treated With Anti-programmed Cell Death Receptor Ligand 1 (PD-L1) Therapy (MK-3475-01C/KEYMAKER-U01C)
- Conditions
- Carcinoma, Non-Small-Cell Lung
- Interventions
- Registration Number
- NCT04165096
- 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 boserolimab (MK-5890), MK-4830, MK-0482 in participants with advanced squamous or non-squamous NSCLC that have been previously treated with anti-PD-L1 therapy.
This study is one of three pembrolizumab substudies being conducted under one pembrolizumab umbrella master protocol (MK-3475-U01/KEYMAKER-U01).
- Detailed Description
The master screening protocol is MK-3475-U01 (KEYMAKER-U01) - NCT04165798
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 135
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 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 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)
- 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 participated in Substudies 1 or 2
- 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 Boserolimab + Pembrolizumab Pembrolizumab On Day 1 of each 3-week cycle, participants receive pembrolizumab 200 mg intravenously (IV) PLUS boserolimab IV for a maximum of 35 cycles (approximately 2 years). All participants are premedicated 1.5 hours (±30 minutes) before infusion of boserolimab with 50 mg oral (PO) diphenhydramine (or equivalent dose of antihistamine) and 500-1000 mg of acetaminophen PO (or equivalent dose of analgesic). Boserolimab + Pembrolizumab Boserolimab On Day 1 of each 3-week cycle, participants receive pembrolizumab 200 mg intravenously (IV) PLUS boserolimab IV for a maximum of 35 cycles (approximately 2 years). All participants are premedicated 1.5 hours (±30 minutes) before infusion of boserolimab with 50 mg oral (PO) diphenhydramine (or equivalent dose of antihistamine) and 500-1000 mg of acetaminophen PO (or equivalent dose of analgesic). 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). Boserolimab + Pembrolizumab acetaminophen On Day 1 of each 3-week cycle, participants receive pembrolizumab 200 mg intravenously (IV) PLUS boserolimab IV for a maximum of 35 cycles (approximately 2 years). All participants are premedicated 1.5 hours (±30 minutes) before infusion of boserolimab with 50 mg oral (PO) diphenhydramine (or equivalent dose of antihistamine) and 500-1000 mg of acetaminophen PO (or equivalent dose of analgesic). Boserolimab + Pembrolizumab diphenhydramine On Day 1 of each 3-week cycle, participants receive pembrolizumab 200 mg intravenously (IV) PLUS boserolimab IV for a maximum of 35 cycles (approximately 2 years). All participants are premedicated 1.5 hours (±30 minutes) before infusion of boserolimab with 50 mg oral (PO) diphenhydramine (or equivalent dose of antihistamine) and 500-1000 mg of acetaminophen PO (or equivalent dose of analgesic). 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).
- 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 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 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.
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)
Cleveland Clinic Main ( Site 0006)
🇺🇸Cleveland, Ohio, United States
Banner MD Anderson Cancer Center ( Site 0001)
🇺🇸Gilbert, Arizona, United States
City of Hope ( Site 0014)
🇺🇸Duarte, California, 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
MedStar Franklin Square Medical Center ( Site 0033)
🇺🇸Baltimore, Maryland, United States
Massachusetts General Hospital ( Site 0003)
🇺🇸Boston, Massachusetts, United States
Dana Farber Cancer Institute ( Site 0002)
🇺🇸Boston, Massachusetts, United States
Oncology Hematology West, PC DBA Nebraska Cancer Specialists ( Site 0031)
🇺🇸Omaha, Nebraska, United States
Dartmouth Hitchcock Medical Center ( Site 0016)
🇺🇸Lebanon, New Hampshire, United States
John Theurer Cancer Center at Hackensack University Medical Center ( Site 0037)
🇺🇸Hackensack, New Jersey, United States
Laura and Isaac Perlmutter Cancer Center ( Site 0034)
🇺🇸New York, New York, United States
Sanford Fargo Medical Center ( Site 0039)
🇺🇸Fargo, North Dakota, United States
Ohio State University Comprehensive Cancer Center ( Site 0015)
🇺🇸Columbus, Ohio, United States
Abramson Cancer Center of the University of Pennsylvania ( Site 0010)
🇺🇸Philadelphia, Pennsylvania, 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
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
Orszagos Koranyi Pulmonologiai Intezet ( Site 0060)
🇭🇺Budapest, Hungary
Soroka Medical Center ( Site 0072)
🇮🇱Beer-Sheva, Israel
Rambam Health Care Campus-Oncology ( Site 0076)
🇮🇱Haifa, Israel
Shaare Zedek Medical Center ( Site 0075)
🇮🇱Jerusalem, Israel
Meir Medical Center ( Site 0071)
🇮🇱Kfar-Saba, Israel
ICO L Hospitalet ( Site 0090)
🇪🇸Hospitalet de Llobregat, Barcelona, Spain
Hospital Universitario Quiron Madrid ( Site 0091)
🇪🇸Pozuelo de Alarcon, Madrid, Spain
Rabin Medical Center ( Site 0074)
🇮🇱Petah Tikva, Israel
Chaim Sheba Medical Center ( Site 0070)
🇮🇱Ramat Gan, Israel
Sourasky Medical Center ( Site 0077)
🇮🇱Tel Aviv, Israel
Azienda Ospedaliera Universitaria Careggi ( Site 0173)
🇮🇹Florence, Firenze, Italy
Policlinico Gemelli di Roma ( Site 0174)
🇮🇹Roma, Lazio, Italy
IRCCS Ospedale San Raffaele ( Site 0171)
🇮🇹Milano, Italy
Seoul National University Bundang Hospital ( Site 0081)
🇰🇷Seongnam-si, Kyonggi-do, Korea, Republic of
Severance Hospital ( Site 0080)
🇰🇷Seoul, Korea, Republic of
Samsung Medical Center ( Site 0082)
🇰🇷Seoul, Korea, Republic of
Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - P-Klinika Nowotworow Pluca i Klatki Pier
🇵🇱Warszawa, Mazowieckie, Poland
Uniwersyteckie Centrum Kliniczne-Early Clinical Trials Unit ( Site 0150)
🇵🇱Gdansk, Pomorskie, Poland
Szpital Wojewódzki im. Mikoaja Kopernika w Koszalinie-Oddzial Dzienny Chemioterapii ( Site 0152)
🇵🇱Koszalin, Zachodniopomorskie, Poland