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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

PHRR210209-002881

NCT03486873, 3475-587 MK-3475-587 (Other Identifier: Merck) KEYNOTE-587 (Other Identifier: Merck) PFDA CTA 2020-23-07-21 SLMC IERC SL-20132

2020-CT0539

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

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 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 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 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.

Regime Classification Priority
2017 - 2022 Global competitiveness and innovation in health Drug discovery and development
Start Date Duration in Months Target Completion Date Actual Completion Date
2020-10-12 95 2028-09-12 0000-00-00

Ongoing

Institution Classification Region LTO #
Merck Sharp & Dohme (I.A.) LLC Private Business NCR LTO-3000006624320
Institution Region
Merck Sharp & Dohme (I.A.) LLC NCR
Name E-Mail Institution and Institution Address
Priscila Perez priscila.d.perez@merck.com 26/F Philamlife Tower, 8767 Paseo de Roxas, Makati City, 1226 Philippines
Name E-Mail Institution and Institution Address
Priscila Perez priscila.d.perez@merck.com 26/F Philamlife Tower, 8767 Paseo de Roxas, Makati City, 1226 Philippines
Name Expertise Affiliation
Rubi K. Li, MD Medical Oncology St. Luke's Medical Center - Quezon City
Project Location Institutional Ethics Review Board
St. Luke's Medical Center - Quezon City St. Luke's Medical Center Institutional Ethics Review Board

Solid tumors

Overall Survival (OS) [ Time Frame: Up to approximately 10 years ]
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 follow-up.

Duration of Response (DOR) Per Evaluation Criteria Used in the Parent Study [ Time Frame: Up to approximately 10 years ]
DOR is determined by disease assessment and is defined as the time from the earliest date of qualifying response on the parent study until earliest date of disease progression or death from any cause, whichever comes first based upon investigator assessment. The DOR will be presented.
Duration of Complete Response (DOCR) Per Evaluation Criteria Used in the Parent Study [ Time Frame: Up to approximately 10 years ]
DOCR is determined by disease assessment and is defined as the time from the date of complete response (CR) on the parent study until earliest date of disease progression or death from any cause, whichever comes first based upon investigator assessment. The DOCR will be presented.
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) ]
A SAE is defined as any untoward medical occurrence that, at any dose: Results in death, Is life-threatening, Requires inpatient hospitalization or prolongation of existing hospitalization, Results in persistent or significant disability/incapacity or Is a congenital anomaly/birth defect. The number of participants who experience a SAE in this study will be presented.
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) ]
AEOSI for this study include selected preferred terms from Medical Dictionary for Regulatory Activities (MedDRA) version 20.1 for the following higher-level terms: Pneumonitis, Colitis, Hepatitis, Nephritis, Adrenal Insufficiency, Hypophysitis, Hyperthyroidism, Hypothyroidism, Thyroiditis, Type 1 Diabetes Mellitus, Severe Skin Reactions Including Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN): or If grade 3 or higher, Uveitis, Pancreatitis, Myositis, Guillain-Barre Syndrome, Myocarditis, Encephalitis, Sarcoidosis, Infusion Reactions and Myasthenic Syndrome. The number of participants who experience an AEOSI in this study will be presented.
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) ]
ECIs for this study include: 1) An overdose of Sponsor's product, that is not associated with clinical symptoms or abnormal laboratory results or 2) An elevated aspartate aminotransferase (AST) or alanine aminotransferase (ALT) lab value that is ≥3X the upper limit of normal (ULN) and an elevated total bilirubin lab value that is ≥2X ULN and, at the same time, an alkaline phosphatase lab value that is <2X ULN, as determined by way of protocol-specified laboratory testing or unscheduled laboratory testing. The number of participants who experience an ECI in this study will be presented.

Recruiting

  • Argentina
  • Australia
  • Austria
  • Belgium
  • Brazil
  • Canada
  • Chile
  • China
  • Colombia
  • Czech Republic
  • Denmark
  • Finland
  • France
  • Germany
  • Greece
  • Guatemala
  • Hungary
  • Ireland
  • Israel
  • Italy
  • Japan
  • Lithuania
  • Malaysia
  • Netherlands
  • New Zealand
  • Norway
  • Poland
  • Portugal
  • Puerto Rico
  • Russia
  • Singapore
  • South Africa
  • South Korea
  • Spain
  • Sweden
  • Switzerland
  • Taiwan
  • Turkey
  • United Kingdom
  • United States

Clinical Trial

NCT03486873, 3475-587 MK-3475-587 (Other Identifier: Merck) KEYNOTE-587 (Other Identifier: Merck) PFDA CTA 2020-23-07-21 SLMC IERC SL-20132

20200505113939

2020-07-23

0000-00-00

3

1

Study is still ongoing

2020-10-12

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.
Non-small cell lung cancer (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)

 

Interventional

Drug: Pembrolizumab 200 or 400 mg IV infusion Other Names: MK-3475 KEYTRUDA® Drug: Standard of Care (SOC) IV infusion or oral tablets

Experimental: Pembrolizumab 200 mg
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.
Intervention: Drug: Pembrolizumab

Experimental: Pembrolizumab 400 mg
Participants receive pembrolizumab 400 mg via intravenous (IV) infusion on Day 1 of each 6-week cycle for up to 17 administrations or more for First Course participants and up to 8 administrations for Second Course participants.
Intervention: Drug: Pembrolizumab

Experimental: Pembrolizumab 200 mg + 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.
Interventions:
Drug: Pembrolizumab
Drug: Standard of Care (SOC)

Experimental: Pembrolizumab 400 mg + SOC (Per Parent Study)
Participants receive pembrolizumab 400 mg via IV infusion on Day 1 of each 6-week cycle PLUS SOC treatment (or per parent study if there is no SOC) for up to 17 administrations or more for First Course participants and up to 8 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.
Interventions:
Drug: Pembrolizumab
Drug: Standard of Care (SOC)

Active Comparator: SOC (Per Parent Study)

Participants receive the dose matched non-pembrolizumab SOC treatment (e.g. chemotherapy) they were receiving as per parent study protocol.

Intervention:

Drug: Standard of Care (SOC)

Date Amendment Classification Reason
2020-09-21 Amendments related to the protocol Inclusion of pembrolizumab 400 mg Q6W dosing schedule would provide participants and treating investigators with two flexible treatment options: the 400 mg Q6W dose, and the currently available dose of 200 mg Q3W.
2021-06-01 Amendments related to the protocol The dose modification and toxicity management guidelines for irAEs and table were updated. The dose modification and toxicity management guidelines for irAEs and table were updated as requested by the U.S. FDA in an effort to harmonize the presentation of safety information across all FDA approved PD-1/L1 antibody prescribing information.

Non-Randomized

N/A

Unspecified

Parallel

Treatment 

Phase III

Utilization Utilization Info
Publication
Oral Presentation
Drug Literature
Posters
Others

For updates, please refer to ClinicalTrials.gov data: https://clinicaltrials.gov/ct2/show/record/NCT03486873?term=3475-587&draw=2&rank=1

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