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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)

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ClinicalTrials.gov Identifier: NCT03486873
Recruitment Status : Recruiting
First Posted : April 3, 2018
Last Update Posted : May 26, 2020
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Study Description
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Brief 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 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 or disease Intervention/treatment Phase
Solid Tumors Biological: Pembrolizumab Drug: Standard of Care (SOC) Phase 3

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 2300 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : August 21, 2018
Estimated Primary Completion Date : May 10, 2028
Estimated Study Completion Date : May 10, 2028

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
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
Other Name: MK-3475
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.
 Biological: Pembrolizumab
200 mg IV infusion
Other Name: MK-3475

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.
 Drug: Standard of Care (SOC)
IV infusion or oral tablets


Outcome Measures
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Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03486873


Contacts
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Contact: Toll Free Number 1-888-577-8839 Trialsites@merck.com

Locations
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Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
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Study Director: Medical Director Merck Sharp & Dohme Corp.
More Information
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Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT03486873    
Other Study ID Numbers: 3475-587
MK-3475-587 ( Other Identifier: Merck )
2017-004417-42 ( EudraCT Number )
KEYNOTE-587 ( Other Identifier: Merck )
195006 ( Registry Identifier: JAPIC-CTI )
First Posted: April 3, 2018    Key Record Dates
Last Update Posted: May 26, 2020
Last Verified: May 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
URL: http://engagezone.msd.com/ds_documentation.php

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Merck Sharp & Dohme Corp.:
PD1
PD-1
PDL1
PD-L1
Additional relevant MeSH terms:
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Pembrolizumab
Antineoplastic Agents, Immunological
Antineoplastic Agents