A Multicenter, Open-label, Phase 3 Study to Evaluate the Long-term Safety and Efficacy in Participants Who Are Currently on Treatment or in Follow-up in Studies That Include Pembrolizumab
Summary
The purpose of this study is to evaluate the long-term safety and efficacy of pembrolizumab (MK-3475) in participants from previous Merck pembrolizumab-based parent studies who transition into this extension study. This study will consist of three phases: 1) First Course Phase, 2) Survival Follow-up Phase or 3) Second Course Phase. Each participant will transition to this extension study in one of the following three phases, depending on the study phase they were in at the completion of the parent study. Participants who were in the First Course Phase of study treatment with pembrolizumab or lenvatinib in their parent study will enter the First Course Phase of this study and complete up to 35 doses or more every 3 weeks (Q3W) or 17 doses or more every 6 weeks (Q6W) of study treatment with pembrolizumab or a pembrolizumab-based combination or lenvatinib according to arm assignment. Participants who were in the Follow-up Phase in the parent study (post-treatment or Survival Follow-up Phase) will enter the Survival Follow-up Phase of this study. Participants who were in the Second Course Phase in their parent study will enter Second Course Phase of this study and complete up to 17 doses Q3W or 8 doses Q6W of study treatment with pembrolizumab or a pembrolizumab-based combination according to arm assignment. Any participant originating from a parent trial where crossover to pembrolizumab was permitted upon disease progression may be eligible for 35 doses as Q3W or 17 doses Q6W of pembrolizumab (approximately 2 years), if they progress while on the control arm and pembrolizumab is approved for the indication in the country where the potential eligible crossover participant is being evaluated.
Arms & interventions
- DrugPembrolizumab
200 or 400 mg IV infusion
- DrugStandard of Care (SOC)
IV infusion or oral tablets
- DrugLenvatinib
Oral capsules
- DrugOlaparib
300mg or 250mg or 100mg oral tablers
- DrugMK-4280
IV Infusion
- BiologicalMK-4280A
800mg favezelimab + 200mg pembrolizumab IV Infusion
- BiologicalPembrolizumab (+) Berahyaluronidase alfa
395 mg or 790 mg SC administration
Outcome measures
Primary
Overall Survival (OS)
OS is defined as the time from randomization or start of study treatment for non-randomized participants (on the parent study) to death due to any cause. Participants without documented death at the time of analysis will be censored at the date of the last known to be alive.
Time frame: Up to approximately 10 years
Secondary
Modified Progression Free Survival (PFS) Per Evaluation Criteria Used in the Parent Trial
Time frame: Up to approximately 10 years
Modified Event Free Survival (EFS) Per Evaluation Criteria Used in the Parent Trial
Time frame: Up to approximately 10 years
Number of Participants Who Experience Serious Adverse Events (SAEs)
Time frame: Up to approximately 42 months (Up to 90 days after last dose of study treatment)
Number of Participants Who Experience Adverse Events of Special Interest (AEOSI)
Time frame: Up to approximately 40 months (Up to 30 days after last dose of study treatment)
Number of Participants Who Experience Clinically Significant Adverse Events (CSAE)
Time frame: Up to approximately 40 months (Up to 30 days after last dose of study treatment)
Number of Participants Who Experience Events of Clinical Interest (ECI)
Time frame: Up to approximately 40 months (Up to 30 days after last dose of study treatment)
Number of Participants Who Discontinue Study Treatment Due to an AE
Time frame: Up to approximately 39 months
Eligibility criteria
Study locations (65)
Arizona Cancer Center at UMC North ( Site 0018)
Tucson, Arizona, 85719
Comprehensive Blood & Cancer Center [Bakersfield, CA] ( Site 0054)
Bakersfield, California, 93309
California Cancer Associates for Research & Excellence ( Site 0016)
Fresno, California, 93720
Providence Medical Foundation ( Site 0087)
Fullerton, California, 92835
The Angeles Clinic and Research Institute ( Site 0005)
Los Angeles, California, 90025
UCLA Hematology/Oncology - Westwood (Building 100) ( Site 0009)
Los Angeles, California, 90095
University of California, Irvine (UCI) Health - UC Irvine Medical Center ( Site 0076)
Orange, California, 92868
Stanford Cancer Center ( Site 0086)
Palo Alto, California, 94304
UCSF Helen Diller Family Comprehensive Cancer Center ( Site 0004)
San Francisco, California, 94158
Providence Saint John's Health Center ( Site 0059)
Santa Monica, California, 90404
University of Colorado Cancer Center ( Site 0021)
Aurora, Colorado, 80045
Yale Cancer Center ( Site 0014)
New Haven, Connecticut, 06511
Georgetown University Medical Center ( Site 0023)
Washington D.C., District of Columbia, 20007
Holy Cross Hospital, Michael & Dianne Bienes Comp Cancer Ctr ( Site 0022)
Fort Lauderdale, Florida, 33308
Baptist MD Anderson Cancer Center ( Site 0083)
Jacksonville, Florida, 32207
Mount Sinai Medical Center Comprehensive Cancer Center ( Site 0031)
Miami Beach, Florida, 33140
Moffitt Cancer Center ( Site 0011)
Tampa, Florida, 33612
Emory School of Medicine ( Site 0013)
Atlanta, Georgia, 30322
Augusta University ( Site 0077)
Augusta, Georgia, 30912
Northwest Georgia Oncology Centers PC ( Site 0061)
Marietta, Georgia, 30060
Kaiser Permanente Moanalua Medical Center ( Site 0063)
Honolulu, Hawaii, 96813
The University of Chicago ( Site 0020)
Chicago, Illinois, 60637
University of Iowa Hospital and Clinics ( Site 0026)
Iowa City, Iowa, 52242
James Graham Brown Cancer Center ( Site 0058)
Louisville, Kentucky, 40202
Mercy Health-Paducah Cancer Center ( Site 0084)
Paducah, Kentucky, 42003
Women's Cancer Care ( Site 0088)
Covington, Louisiana, 70433
MedStar Franklin Square Medical Center ( Site 0046)
Baltimore, Maryland, 21237
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins ( Site 0056)
Baltimore, Maryland, 21287
Maryland Oncology Hematology (MOH) ( Site 8000)
Columbia, Maryland, 21044
Massachusetts General Hospital ( Site 0041)
Boston, Massachusetts, 02114
Dana-Farber Cancer Institute ( Site 0006)
Boston, Massachusetts, 02215
Karmanos Cancer Institute ( Site 0047)
Detroit, Michigan, 48201
Mayo Clinic in Rochester, Minnesota ( Site 0002)
Rochester, Minnesota, 55905
Comprehensive Cancer Centers of Nevada ( Site 0043)
Las Vegas, Nevada, 89169
John Theurer Cancer Center at Hackensack University Medical Center ( Site 0038)
Hackensack, New Jersey, 07601
Cancer Institute of New Jersey ( Site 0025)
New Brunswick, New Jersey, 08901
Laura and Isaac Perlmutter Cancer Center at NYU Langone Health ( Site 0032)
New York, New York, 10016
Memorial Sloan Kettering Cancer Center ( Site 0012)
New York, New York, 10065
White Plains Hospital-Center for Cancer Care ( Site 0069)
White Plains, New York, 10601
WakeMed Cancer Care - Waverly Hematology & Medical Oncology ( Site 0074)
Cary, North Carolina, 27518
University of North Carolina at Chapel Hill ( Site 0040)
Chapel Hill, North Carolina, 27514
Levine Cancer Institute ( Site 0034)
Charlotte, North Carolina, 28204
Duke Cancer Center ( Site 0028)
Durham, North Carolina, 27710
Sanford Fargo Medical Center-Roger Maris Cancer Center ( Site 0065)
Fargo, North Dakota, 58102
University Hospitals ( Site 0044)
Cleveland, Ohio, 44106
Oklahoma Cancer Specialists and Research Institute, LLC ( Site 0082)
Tulsa, Oklahoma, 74146
Providence Portland Medical Center ( Site 0051)
Portland, Oregon, 97225
St. Luke's University Health Network ( Site 0017)
Bethlehem, Pennsylvania, 18015
University of Pennsylvania ( Site 0010)
Philadelphia, Pennsylvania, 19104
Fox Chase Cancer Center ( Site 0042)
Philadelphia, Pennsylvania, 19111
UPMC Hillman Cancer Center ( Site 0008)
Pittsburgh, Pennsylvania, 15232
Saint Francis Health System ( Site 0089)
Greenville, South Carolina, 29607
Sanford Cancer Center ( Site 0066)
Sioux Falls, South Dakota, 57104
West Cancer Center and Research Institute ( Site 0055)
Germantown, Tennessee, 38138
Vanderbilt Health One Hundred Oaks Diagnostic ( Site 0060)
Nashville, Tennessee, 37204
Vanderbilt Ingram Cancer Center ( Site 0015)
Nashville, Tennessee, 37232
Texas Oncology - Central/South Texas ( Site 8001)
Austin, Texas, 78745
Texas Oncology-Baylor Sammons Cancer Center ( Site 0062)
Dallas, Texas, 75246
University of Texas MD Anderson Cancer Center ( Site 0007)
Houston, Texas, 77030
South Texas Accelerated Research Therapeutics, LLC (START) ( Site 0001)
San Antonio, Texas, 78229
University of Virginia Health System ( Site 0035)
Charlottesville, Virginia, 22908
Bon Secours St. Francis Medical Center-Oncology Research ( Site 0075)
Midlothian, Virginia, 23114
VCU Health Adult Outpatient Pavillion ( Site 0080)
Richmond, Virginia, 23219
Blue Ridge Cancer Care ( Site 0067)
Roanoke, Virginia, 24014
Fred Hutchinson Cancer Center ( Site 0024)
Seattle, Washington, 98109
References
- Robert C, Carlino MS, McNeil C, Ribas A, Grob JJ, Schachter J, Nyakas M, Kee D, Petrella TM, Blaustein A, Lotem M, Arance A, Daud AI, Hamid O, Larkin J, Anderson J, Krepler C, Grebennik D, Long GV. Seven-Year Follow-Up of the Phase III KEYNOTE-006 Study: Pembrolizumab Versus Ipilimumab in Advanced Melanoma. J Clin Oncol. 2023 Aug 20;41(24):3998-4003. doi: 10.1200/JCO.22.01599. Epub 2023 Jun 22.(PubMed)
- Long GV, Carlino MS, McNeil C, Ribas A, Gaudy-Marqueste C, Schachter J, Nyakas M, Kee D, Petrella TM, Blaustein A, Lotem M, Arance AM, Daud AI, Hamid O, Larkin J, Yao L, Singh R, Lal R, Robert C. Pembrolizumab versus ipilimumab for advanced melanoma: 10-year follow-up of the phase III KEYNOTE-006 study. Ann Oncol. 2024 Dec;35(12):1191-1199. doi: 10.1016/j.annonc.2024.08.2330. Epub 2024 Sep 15.(PubMed)