Clinical Trial - NCT03486873

Long-term Safety and Efficacy Extension Study for Participants With Advanced Tumors Who Are Currently on Treatment or in Follow-up in a Pembrolizumab (MK-3475) Study (MK-3475-587/KEYNOTE-587)

Recruiting

Sponsor: Merck Sharp & Dohme Corp.

Collaborators:

Information provided by (Responsible party): Sponsor

ClinicalTrials.gov Identifier: NCT03486873

Protocol Info

Short Description: Phase III Extension Trial of Pembrolizumab in Advanced Tumors
Long Description: A Multicenter, Open label, Phase III Extension Trial to Study the Long-term Safety and Efficacy in Participants with Advanced Tumors Who Are Currently on Treatment or in Follow-up in a Pembrolizumab Trial.
MGH Status: Open
Sponsor: Merck
Disease Program: Melanoma

Next Steps


If you are interested in this protocol or in other treatment options at Massachusetts General Hospital, please Request a Consultation.




Purpose

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 roll-over 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 roll-over 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 in their parent study will enter the First Course Phase of this study and complete up to 35 cycles of study treatment with pembrolizumab or a pembrolizumab-based combination. 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 cycles of study treatment with pembrolizumab or a pembrolizumab-based combination. Any participant originating from a parent trial where crossover to pembrolizumab was permitted upon disease progression may be eligible for 35 doses (approximately 2 years) of pembrolizumab, 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.
Condition Title Intervention Phase
Solid Tumors Pembrolizumab Standard of Care (SOC) Phase 3
Study Type Interventional
Official Title A Multicenter, Open Label, Phase III Extension Trial to Study the Long-term Safety and Efficacy in Participants With Advanced Tumors Who Are Currently on Treatment or in Follow-up in a Pembrolizumab Trial

Primary Outcome Measures

Overall Survival (OS) [Time Frame: Up to approximately 10 years] [Designated as safety issue: ]


Secondary Outcome Measures

Duration of Response (DOR) Per Evaluation Criteria Used in the Parent Study [Time Frame: Up to approximately 10 years] [Designated as safety issue: ]

Duration of Complete Response (DOCR) Per Evaluation Criteria Used in the Parent Study [Time Frame: Up to approximately 10 years] [Designated as safety issue: ]

Serious Adverse Events (SAEs) [Time Frame: Up to approximately 42 months (Up to 90 days after last dose of study treatment)] [Designated as safety issue: ]

Adverse Events of Special Interest (AEOSI) [Time Frame: Up to approximately 40 months (Up to 30 days after last dose of study treatment)] [Designated as safety issue: ]

Events of Clinical Interest (ECI) [Time Frame: Up to approximately 40 months (Up to 30 days after last dose of study treatment)] [Designated as safety issue: ]

Estimated Enrollment: 2300
Study Start Date: August 2018
Estimated Study Completion Date: May 2028
Estimated Primary Completion Date: May 2028
Arms Assigned Interventions

Experimental:Pembrolizumab

Participants receive pembrolizumab 200 mg via intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 35 administrations or more for First Course participants and up to 17 administrations for Second Course participants.
Biological:Pembrolizumab
200 mg IV infusion

Experimental:Pembrolizumab+SOC (Per Parent Study)

Participants receive pembrolizumab 200 mg via IV infusion on Day 1 of each 3-week cycle PLUS standard of care (SOC) treatment (or per parent study if there is no SOC) for up to 35 administrations or more for First Course participants and up to 17 administrations for Second Course participants. Participants receiving a pembrolizumab-based combination treatment will receive the dose regimen of the combination drug(s) which is recommended per SOC, or was used in the parent study protocol if there is no SOC recommendation.
Drug:Standard of Care (SOC)
IV infusion or oral tablets

Active Comparator:SOC (Per Parent Study)

Participants receive the same non-pembrolizumab SOC treatment (e.g. chemotherapy) they were receiving in the parent study for up to 35 administrations or more for First Course participants and up to 17 administrations for Second Course participants.

Eligibility

Ages Eligible for Study: N/A-N/A

Genders Eligible for Study: All

Accepts Healthly Volunteers: No

Inclusion Criteria:

  • Advanced unresectable or metastatic tumor(s)
  • Currently enrolled in a Merck-sponsored pembrolizumab study and is receiving study treatment or in a Follow-up Phase at the time MK-3475-587 is open. The parent studies must have completed all regulatory requirements and submissions, if any, or have fully addressed their primary endpoint(s) before all their participants roll over into this MK-3475-587 extension study.

Additional eligibility criteria for participants who enter Second Course Phase once they are enrolled on MK-3475-587:

  • Has not received any anticancer systemic treatment since the last dose of pembrolizumab or a pembrolizumab-based combination in First Course Phase
  • Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Demonstrates adequate organ function
  • Have resolution of any toxic effect(s) of First Course Phase trial treatment with pembrolizumab or a pembrolizumab-based combination to Grade 1 or less (except alopecia) before trial treatment in Second Course Phase is started. If participant received major surgery or radiation therapy of >30 Gray (Gy), they must have recovered from the toxicity and/or complications of the intervention.
  • Male participant must agree to use contraception during the Second Course Phase study treatment period and for ≥120 days, corresponding to time needed to eliminate any study combination treatment(s), plus 75 days (a spermatogenesis cycle) for study treatments with evidence of genotoxicity at any dose after the last dose of study treatment and refrain from donating sperm during this period.
  • A female participant is eligible to enroll if she is not pregnant, not breastfeeding, and ≥1 of the following conditions applies: A woman of childbearing potential (WOCBP) who agrees to use contraception during the study treatment period and for ≥120 days (corresponding to time needed to eliminate any study combination treatment(s) plus 30 days (a menstruation cycle) for study treatments with risk of genotoxicity.

Exclusion Criteria:

  • There are no exclusion criteria to participate in MK-3475-587.

Participants are excluded from entering Second Course trial treatment once they are enrolled on MK-3475-587 if any of the following criteria applies:

  • Has severe hypersensitivity (≥ Grade 3) to pembrolizumab and/or any of its excipients
  • Has received a live vaccine within 30 days prior to the first dose of Second Course Phase trial treatment
  • 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 to the Cycle 1 Day 1 of Second Course Phase
  • Has a known additional malignancy that is progressing or requires active treatment. Exceptions include early stage cancers (carcinoma in situ or Stage 1) treated with curative intent, melanoma (non-ulcerated, thin primary), basal cell carcinoma of the skin, squamous cell carcinoma of the skin, in situ cervical cancer, or in situ breast cancer that has undergone potentially curative therapy.
  • Has known active central nervous system metastases and/or carcinomatous meningitis
  • Has an active autoimmune disease that has required systemic treatment in the past 2 years (i.e., use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed.
  • Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis. Note: Participants that experienced pneumonitis during First Course that did not meet the criteria for permanent discontinuation are eligible.
  • NSCLC participants only: Has interstitial lung disease
  • Has an active infection requiring systemic therapy
  • Has a known history of human immunodeficiency virus (HIV) infection.
  • Has a known history of or is positive for hepatitis B or hepatitis C
  • Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the Second Course Phase eligibility Visit through 120 days after the last dose of study treatment.
  • Has severe cardiovascular disease, i.e., arrhythmias, requiring chronic treatment, congestive heart failure (New York Heart Association Class III or IV) or symptomatic ischemic heart disease.
  • Has hepatic decompensation (Child-Pugh score >6 [class B and C])
  • Has uncontrolled thyroid dysfunction
  • Has uncontrolled diabetes mellitus
  • Has had an allogeneic tissue/solid organ transplant
  • Has a known history of active tuberculosis (TB; Bacillus tuberculosis)

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT03486873

Locations

  • United States, Arizona
    • University of Arizona Cancer Center ( Site 0018) Tucson, Arizona, United States, 85724
  • United States, California
    • California Cancer Associates for Research & Excellence ( Site 0016) Fresno, California, United States, 93720
    • The Angeles Clinic and Research Institute ( Site 0005) Los Angeles, California, United States, 90025
    • UCLA Medical Center Hematology Oncology ( Site 0009) Los Angeles, California, United States, 90095
    • UCSF Helen Diller Family Comprehensive Cancer Center ( Site 0004) San Francisco, California, United States, 94115
  • United States, Colorado
    • University of Colorado Cancer Center ( Site 0021) Aurora, Colorado, United States, 80045
  • United States, Connecticut
    • Yale Cancer Center ( Site 0014) New Haven, Connecticut, United States, 06511
  • United States, Florida
    • Holy Cross Hospital, Michael & Dianne Bienes Comp Cancer Ctr ( Site 0022) Fort Lauderdale, Florida, United States, 33308
    • Mount Sinai Medical Center Comprehensive Cancer Center ( Site 0031) Miami Beach, Florida, United States, 33140
    • Moffitt Cancer Center ( Site 0011) Tampa, Florida, United States, 33612
  • United States, Georgia
    • Emory University ( Site 0013) Atlanta, Georgia, United States, 30322
  • United States, Illinois
    • The University of Chicago ( Site 0020) Chicago, Illinois, United States, 60637
  • United States, Iowa
    • University of Iowa Hospital and Clinics ( Site 0026) Iowa City, Iowa, United States, 52242
  • United States, Massachusetts
    • Massachusetts General Hospital ( Site 0041) Boston, Massachusetts, United States, 02114
    • Dana-Farber Cancer Institute ( Site 0006) Boston, Massachusetts, United States, 02215
  • United States, Minnesota
    • Mayo Clinic Rochester - St. Mary's Hospital ( Site 0002) Rochester, Minnesota, United States, 55905
  • United States, New Jersey
    • John Theurer Cancer Center at Hackensack University Med Ctr ( Site 0038) Hackensack, New Jersey, United States, 07601
    • Cancer Institute of New Jersey ( Site 0025) New Brunswick, New Jersey, United States, 08903
  • United States, New York
    • Memorial Sloan Kettering Cancer Center ( Site 0012) New York, New York, United States, 10065
  • United States, North Carolina
    • Levine Cancer Institute ( Site 0034) Charlotte, North Carolina, United States, 28204
    • Duke Cancer Center ( Site 0028) Durham, North Carolina, United States, 27710
  • United States, Pennsylvania
    • St. Luke's University Health Network ( Site 0017) Easton, Pennsylvania, United States, 18045
    • University of Pennsylvania ( Site 0010) Philadelphia, Pennsylvania, United States, 19104
    • UPMC Hillman Cancer Center ( Site 0008) Pittsburgh, Pennsylvania, United States, 15232
  • United States, Texas
    • University of Texas MD Anderson Cancer Center ( Site 0007) Houston, Texas, United States, 77030
    • South Texas Accelerated Research Therapeutics, LLC (START) ( Site 0001) San Antonio, Texas, United States, 78229
  • United States, Virginia
    • University of Virginia Health System ( Site 0035) Charlottesville, Virginia, United States, 22908
  • Australia, New South Wales
    • Calvary Mater Newcastle ( Site 3005) Waratah, New South Wales, Australia, 2298
    • Westmead Hospital ( Site 3000) Westmead, New South Wales, Australia, 2145
    • Melanoma Institute Australia ( Site 3001) Wollstonecraft, New South Wales, Australia, 2065
  • Australia, Queensland
    • Princess Alexandra Hospital ( Site 3002) Brisbane, Queensland, Australia, 4102
  • Australia, Western Australia
    • Sir Charles Gairdner Hospital ( Site 3006) Nedlands, Western Australia, Australia, 6009
  • Australia,
    • Chris OBrien Lifehouse ( Site 3003) Camperdown, , Australia, 2050
    • Austin Health-Austin Hospital ( Site 3004) Heidelberg, , Australia, 3084
  • Austria,
    • Medical University of Graz ( Site 2952) Graz, , Austria, 8036
    • Medizinische Universitaet Innsbruck ( Site 2951) Innsbruck, , Austria, 6020
    • Medizinische Universitaet Wien, Universitaetsklinik fuer Dermatologie ( Site 2953) Wien, , Austria, 1090
  • Belgium,
    • UZ Brussel ( Site 2900) Brussels, , Belgium, 1090
    • UZ Leuven ( Site 2901) Leuven, , Belgium, 3000
  • Canada, Alberta
    • Cross Cancer Institute ( Site 2804) Edmonton, Alberta, Canada, T6G 1Z2
  • Canada, Ontario
    • Juravinski Cancer Centre ( Site 2801) Hamilton, Ontario, Canada, L8V 5C2
    • Sunnybrook Research Institute ( Site 2802) Toronto, Ontario, Canada, M4N 3M5
    • Princess Margaret Cancer Centre ( Site 2803) Toronto, Ontario, Canada, M5G 2M9
  • Canada, Quebec
    • Jewish General Hospital ( Site 2800) Montreal, Quebec, Canada, H3T 1E2
  • Chile,
    • Fundacion Arturo Lopez Perez FALP ( Site 2750) Santiago, , Chile, 7500921
  • Colombia, Valle Del Cauca
    • Fundacion Valle del Lili ( Site 2700) Cali, Valle Del Cauca, Colombia, 760032
  • France,
    • Institut Bergonie ( Site 2502) Bordeaux, , France, 33076
    • Ambroise Pare Hopital ( Site 2503) Boulogne, , France, 92100
    • CHU de Brest. Hopital Morvan ( Site 2504) Brest, , France, 29200
    • Hopital Trousseau ( Site 2512) Chambray-Les-Tours, , France, 37170
    • CHRU Lille Hospital Claude Huriez ( Site 2506) Lille, , France, 59037
    • CHU La Timone ( Site 2508) Marseille, , France, 13385
    • Hopital Cochin ( Site 2509) Paris, , France, 75006
    • Hopital Saint Louis ( Site 2510) Paris, , France, 75010
    • C.H.U. Pontchaillou ( Site 2511) Rennes, , France, 35033
    • Institut Gustave Roussy ( Site 2513) Villejuif, , France, 94800
  • Germany,
    • Elbe Klinikum Buxtehude ( Site 2400) Buxtehude, , Germany, 21614
    • Universitaetsklinikum Essen ( Site 2404) Essen, , Germany, 45122
    • SRH Wald-Klinikum Gera GmbH ( Site 2403) Gera, , Germany, 07548
    • Medizinische Hochschule Hannover ( Site 2402) Hannover, , Germany, 30625
    • Universitaetsklinik Muenchen ( Site 2406) Muenchen, , Germany, 80337
    • Universitaetsklinikum Tuebingen ( Site 2405) Tuebingen, , Germany, 72076
  • Israel,
    • Rambam Medical Center ( Site 2053) Haifa, , Israel, 3109601
    • Hadassah Ein Kerem Medical Center ( Site 2051) Jerusalem, , Israel, 9112001
    • Chaim Sheba Medical Center. ( Site 2052) Ramat Gan, , Israel, 5265601
  • Italy,
    • Istituto Nazionale Tumori IRCCS Fondazione Pascale ( Site 1955) Napoli, , Italy, 80131
  • Korea, Republic of, Gyeonggi-do
    • Seoul National University Bundang Hospital ( Site 0951) Seongnam-si, Gyeonggi-do, Korea, Republic of, 13620
  • Korea, Republic of,
    • Seoul National University Hospital ( Site 0953) Seoul, , Korea, Republic of, 03080
    • Asan Medical Center ( Site 0952) Seoul, , Korea, Republic of, 05505
    • Samsung Medical Center ( Site 0950) Seoul, , Korea, Republic of, 06351
  • Netherlands,
    • Universitair Medisch Centrum Groningen ( Site 1550) Groningen, , Netherlands, 9713 GZ
  • New Zealand,
    • Canterbury Regional Cancer & Blood Service ( Site 1500) Christchurch, , New Zealand, 8011
    • Capital & Coast District Health Board - Wellington Hospital ( Site 1501) Wellington, , New Zealand, 6021
  • Norway,
    • Helse Bergen Haukeland universitetssykehus ( Site 1451) Bergen, , Norway, 5021
    • Oslo Universitetssykehus Radiumhospitalet ( Site 1450) Oslo, , Norway, 0379
  • Spain,
    • H.U. Vall de Hebron ( Site 0850) Barcelona, , Spain, 08035
    • Hospital Clinic de Barcelona ( Site 0852) Barcelona, , Spain, 08036
    • Hospital Germans Trias i Pujol ( Site 0851) Barcelona, , Spain, 08916
    • Clinica Universitaria de Navarra ( Site 0855) Madrid, , Spain, 28027
    • Hospital General Universitario 12 de Octubre ( Site 0856) Madrid, , Spain, 28041
    • Hospital Universitario La Paz ( Site 0853) Madrid, , Spain, 28046
    • Hospital General Universitario de Valencia ( Site 0854) Valencia, , Spain, 46014
  • Sweden,
    • Karolinska Universitetssjukhuset Solna ( Site 0802) Stockholm, , Sweden, 171 76
    • Norrlands Universitetssjukhus ( Site 0800) Umea, , Sweden, 901 85
    • Blod och Tumorssjukdomar. Akademiska sjukhuset ( Site 0801) Uppsala, , Sweden, 751 85
  • Switzerland,
    • Universitaetsspital Zuerich ( Site 0750) Zuerich, , Switzerland, 8091
  • United Kingdom,
    • Mid Essex Hospitals Service Trust. Broomfield Hospital ( Site 0503) Broomfield, , United Kingdom, CM1 7ET
    • Western General Hospital ( Site 0502) Edinburgh, , United Kingdom, EH4 2XU
    • Royal Free Hospital ( Site 0507) London, , United Kingdom, NW3 2QG
    • Royal Marsden Hospital ( Site 0505) London, , United Kingdom, SW3 6JJ
    • Sarah Cannon Research UK ( Site 0504) London, , United Kingdom, W1G 6AD

Sponsors and Collaborators

Merck Sharp & Dohme Corp.

More Information

No publications provided

Responsible Party: Sponsor
ClinicalTrials.gov Identifier: NCT03486873
Other Study ID Numbers: MK-3475-587
Study First Received:
Last Updated:
Health Authority:

Keywords provided by Merck Sharp & Dohme Corp.:

PD1

PD-1

PDL1

PD-L1

Additional relevant MeSH terms:

Pembrolizumab

Next Steps


If you are interested in this protocol or in other treatment options at Massachusetts General Hospital, please Request a Consultation.







ClinicalTrials.gov processed this data on August 15, 2019