RECRUITING

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)

Conditions

Solid Tumors Hematologic Malignancies PD1 PD-1 PDL1 PD-L1

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

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

Quick Facts

Study Start:2018-08-21

Study Completion:2043-08-04

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT03486873

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* Treated on the parent pembrolizumab studies established by the Sponsor as MK-3475-587 ready. * Currently receiving pembrolizumab, pembrolizumab based combinations or lenvatinib from parent studies or in a follow-up phase. * 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. * 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. * Adequately controlled blood pressure (BP) to \<150/90 mmHg, with or without antihypertensive medications. * For male agrees to be abstinent from penile-vaginal intercourse OR agrees to use a highly effective contraceptive method while receiving study drug and for 7 days after the last dose of lenvatinib. * Is female and not pregnant/breastfeeding and at least one of the following applies during the study and for ≥4 days after: is not a woman of childbearing potential (WOCBP), is a WOCBP and uses highly effective contraception (low user dependency method OR a user dependent hormonal method in combination with a barrier method) or is a WOCBP who is abstinent from heterosexual intercourse.	* 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. For parent studies where inclusion of participants with hepatitis was permitted, MK-3475-587 will follow the parent study eligibility criteria for hepatitis. * 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). * Has had major surgery within 3 weeks prior to first dose of study intervention(s). * Has preexisting ≥Grade 3 gastrointestinal or non-gastrointestinal fistula. * Has urine protein ≥1 g/24 hours. * Has LVEF below the institutional (or local laboratory) normal range, as determined by multigated acquisition scan (MUGA) or echocardiogram (ECHO). * Has radiographic evidence of encasement or invasion of a major blood vessel, or of intratumoral cavitation. * Prolongation of QT intervals corrected for heart rate using Fridericia's (cube root) correction (QTcF) interval to \>480 ms. * Has clinically significant cardiovascular disease within 12 months from first dose of study intervention, including New York Heart Association Class III or IV congestive heart failure, unstable angina, myocardial infarction, cerebral vascular accident, or cardiac arrhythmia associated with hemodynamic instability. * Gastrointestinal malabsorption or any other condition that might affect the absorption of lenvatinib. * Active hemoptysis (bright red blood of at least 0.5 teaspoon) within 3 weeks prior to the first dose of study drug. * Has a history of any contraindication or has a severe hypersensitivity to any components of lenvatinib.

Inclusion Criteria

Exclusion Criteria

* Treated on the parent pembrolizumab studies established by the Sponsor as MK-3475-587 ready.
* Currently receiving pembrolizumab, pembrolizumab based combinations or lenvatinib from parent studies or in a follow-up phase.
* 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.
* 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.
* Adequately controlled blood pressure (BP) to \<150/90 mmHg, with or without antihypertensive medications.
* For male agrees to be abstinent from penile-vaginal intercourse OR agrees to use a highly effective contraceptive method while receiving study drug and for 7 days after the last dose of lenvatinib.
* Is female and not pregnant/breastfeeding and at least one of the following applies during the study and for ≥4 days after: is not a woman of childbearing potential (WOCBP), is a WOCBP and uses highly effective contraception (low user dependency method OR a user dependent hormonal method in combination with a barrier method) or is a WOCBP who is abstinent from heterosexual intercourse.

* 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. For parent studies where inclusion of participants with hepatitis was permitted, MK-3475-587 will follow the parent study eligibility criteria for hepatitis.
* 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).
* Has had major surgery within 3 weeks prior to first dose of study intervention(s).
* Has preexisting ≥Grade 3 gastrointestinal or non-gastrointestinal fistula.
* Has urine protein ≥1 g/24 hours.
* Has LVEF below the institutional (or local laboratory) normal range, as determined by multigated acquisition scan (MUGA) or echocardiogram (ECHO).
* Has radiographic evidence of encasement or invasion of a major blood vessel, or of intratumoral cavitation.
* Prolongation of QT intervals corrected for heart rate using Fridericia's (cube root) correction (QTcF) interval to \>480 ms.
* Has clinically significant cardiovascular disease within 12 months from first dose of study intervention, including New York Heart Association Class III or IV congestive heart failure, unstable angina, myocardial infarction, cerebral vascular accident, or cardiac arrhythmia associated with hemodynamic instability.
* Gastrointestinal malabsorption or any other condition that might affect the absorption of lenvatinib.
* Active hemoptysis (bright red blood of at least 0.5 teaspoon) within 3 weeks prior to the first dose of study drug.
* Has a history of any contraindication or has a severe hypersensitivity to any components of lenvatinib.

Contacts and Locations

Study Contact

Toll Free Number

CONTACT

1-888-577-8839

Trialsites@msd.com

Principal Investigator

Medical Director

STUDY_DIRECTOR

Merck Sharp & Dohme LLC

Study Locations (Sites)

Arizona Cancer Center at UMC North ( Site 0018)

Tucson, Arizona, 85719

United States

Comprehensive Blood & Cancer Center [Bakersfield, CA] ( Site 0054)

Bakersfield, California, 93309

United States

California Cancer Associates for Research & Excellence ( Site 0016)

Fresno, California, 93720

United States

Providence Medical Foundation ( Site 0087)

Fullerton, California, 92835

United States

The Angeles Clinic and Research Institute ( Site 0005)

Los Angeles, California, 90025

United States

UCLA Hematology/Oncology - Westwood (Building 100) ( Site 0009)

Los Angeles, California, 90095

United States

University of California, Irvine (UCI) Health - UC Irvine Medical Center ( Site 0076)

Orange, California, 92868

United States

UCSF Helen Diller Family Comprehensive Cancer Center ( Site 0004)

San Francisco, California, 94158

United States

Providence Saint John's Health Center ( Site 0059)

Santa Monica, California, 90404

United States

University of Colorado Cancer Center ( Site 0021)

Aurora, Colorado, 80045

United States

Yale Cancer Center ( Site 0014)

New Haven, Connecticut, 06511

United States

Georgetown University Medical Center ( Site 0023)

Washington, District of Columbia, 20007

United States

Holy Cross Hospital, Michael & Dianne Bienes Comp Cancer Ctr ( Site 0022)

Fort Lauderdale, Florida, 33308

United States

Baptist MD Anderson Cancer Center ( Site 0083)

Jacksonville, Florida, 32207

United States

Mount Sinai Medical Center Comprehensive Cancer Center ( Site 0031)

Miami Beach, Florida, 33140

United States

Moffitt Cancer Center ( Site 0011)

Tampa, Florida, 33612

United States

Emory School of Medicine ( Site 0013)

Atlanta, Georgia, 30322

United States

Augusta University ( Site 0077)

Augusta, Georgia, 30912

United States

Northwest Georgia Oncology Centers PC ( Site 0061)

Marietta, Georgia, 30060

United States

Kaiser Permanente Moanalua Medical Center ( Site 0063)

Honolulu, Hawaii, 96813

United States

The University of Chicago ( Site 0020)

Chicago, Illinois, 60637

United States

University of Iowa Hospital and Clinics ( Site 0026)

Iowa City, Iowa, 52242

United States

James Graham Brown Cancer Center ( Site 0058)

Louisville, Kentucky, 40202

United States

Mercy Health-Paducah Cancer Center ( Site 0084)

Paducah, Kentucky, 42003

United States

Women's Cancer Care ( Site 0088)

Covington, Louisiana, 70433

United States

MedStar Franklin Square Medical Center ( Site 0046)

Baltimore, Maryland, 21237

United States

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins ( Site 0056)

Baltimore, Maryland, 21287

United States

Massachusetts General Hospital ( Site 0041)

Boston, Massachusetts, 02114

United States

Dana-Farber Cancer Institute ( Site 0006)

Boston, Massachusetts, 02215

United States

Karmanos Cancer Institute ( Site 0047)

Detroit, Michigan, 48201

United States

Mayo Clinic in Rochester, Minnesota ( Site 0002)

Rochester, Minnesota, 55905

United States

Comprehensive Cancer Centers of Nevada ( Site 0043)

Las Vegas, Nevada, 89169

United States

John Theurer Cancer Center at Hackensack University Medical Center ( Site 0038)

Hackensack, New Jersey, 07601

United States

Cancer Institute of New Jersey ( Site 0025)

New Brunswick, New Jersey, 08903

United States

Laura and Isaac Perlmutter Cancer Center at NYU Langone Health ( Site 0032)

New York, New York, 10016

United States

Memorial Sloan Kettering Cancer Center ( Site 0012)

New York, New York, 10065

United States

White Plains Hospital-Center for Cancer Care ( Site 0069)

White Plains, New York, 10601

United States

WakeMed Cancer Care - Waverly Hematology & Medical Oncology ( Site 0074)

Cary, North Carolina, 27518

United States

University of North Carolina at Chapel Hill ( Site 0040)

Chapel Hill, North Carolina, 27599

United States

Levine Cancer Institute ( Site 0034)

Charlotte, North Carolina, 28204

United States

Duke Cancer Center ( Site 0028)

Durham, North Carolina, 27710

United States

Sanford Fargo Medical Center-Roger Maris Cancer Center ( Site 0065)

Fargo, North Dakota, 58122

United States

University Hospitals ( Site 0044)

Cleveland, Ohio, 44106

United States

Oklahoma Cancer Specialists and Research Institute, LLC ( Site 0082)

Tulsa, Oklahoma, 74146

United States

Providence Portland Medical Center ( Site 0051)

Portland, Oregon, 97225

United States

St. Luke's University Health Network ( Site 0017)

Bethlehem, Pennsylvania, 18015

United States

University of Pennsylvania ( Site 0010)

Philadelphia, Pennsylvania, 19104

United States

Fox Chase Cancer Center ( Site 0042)

Philadelphia, Pennsylvania, 19111

United States

UPMC Hillman Cancer Center ( Site 0008)

Pittsburgh, Pennsylvania, 15232

United States

Sanford Cancer Center ( Site 0066)

Sioux Falls, South Dakota, 57104

United States

West Cancer Center and Research Institute ( Site 0055)

Germantown, Tennessee, 38138

United States

Vanderbilt Health One Hundred Oaks Diagnostic ( Site 0060)

Nashville, Tennessee, 37204

United States

Vanderbilt Ingram Cancer Center ( Site 0015)

Nashville, Tennessee, 37232

United States

Texas Oncology-Baylor Sammons Cancer Center ( Site 0062)

Dallas, Texas, 75246

United States

University of Texas MD Anderson Cancer Center ( Site 0007)

Houston, Texas, 77030

United States

South Texas Accelerated Research Therapeutics, LLC (START) ( Site 0001)

San Antonio, Texas, 78229

United States

University of Virginia Health System ( Site 0035)

Charlottesville, Virginia, 22908

United States

Bon Secours St. Francis Medical Center-Oncology Research ( Site 0075)

Midlothian, Virginia, 23114

United States

Blue Ridge Cancer Care ( Site 0067)

Roanoke, Virginia, 24014

United States

Fred Hutchinson Cancer Center ( Site 0024)

Seattle, Washington, 98109

United States

Collaborators and Investigators

Sponsor: Merck Sharp & Dohme LLC

Medical Director, STUDY_DIRECTOR, Merck Sharp & Dohme LLC

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2018-08-21

Study Completion Date2043-08-04

Study Record Updates

Study Start Date2018-08-21

Study Completion Date2043-08-04

Terms related to this study

Keywords Provided by Researchers

PD1
PD-1
PDL1
PD-L1

Additional Relevant MeSH Terms

Solid Tumors
Hematologic Malignancies