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)

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 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.

Conditions

  • Solid Tumors
  • Hematologic Malignancies

Eligibility

Eligible Ages
Over 18 Years
Eligible Sex
All
Accepts Healthy Volunteers
No

Inclusion 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. 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. - 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. Additional eligibility criteria for participants who enter dosing with Lenvatinib: - 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.

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. 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). Additional exclusion criteria for participants who enter dosing with Lenvatinib: - 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.

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
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.
  • Drug: Pembrolizumab
    200 or 400 mg IV infusion
    Other names:
    • MK-3475
    • KEYTRUDA®
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.
  • Drug: Pembrolizumab
    200 or 400 mg IV infusion
    Other names:
    • MK-3475
    • KEYTRUDA®
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.
  • 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 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.
  • Drug: Pembrolizumab
    200 or 400 mg IV infusion
    Other names:
    • MK-3475
    • KEYTRUDA®
  • Drug: Standard of Care (SOC)
    IV infusion or oral tablets
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.
  • Drug: Standard of Care (SOC)
    IV infusion or oral tablets
Experimental
Lenvatinib 20 mg 		Participants with body weight (BW)>60kg receive Lenvatinib 20mg orally once daily on a 21 or 42 day cycle. It is taken 0-4 hours after completion of pembrolizumabd administration in the clinic on cycle 1 day 1(C1D1), C2D1, C3D1, etc. Taken at home on all other days.
  • Drug: Lenvatinib
    Oral capsules
Experimental
Lenvatinib 24 mg 		Participants with body weight (BW)>60 kg receive Lenvatinib 24 mg orally once daily on a 21 or 42 day cycle. It is taken 0-4 hours after completion of pembrolizumabd administration in the clinic on cycle 1 day 1(C1D1), C2D1, C3D1, etc. Taken at home on all other days.
  • Drug: Lenvatinib
    Oral capsules
Experimental
Lenvatinib 12 mg 		Participants with body weight (BW)>60 kg receive Lenvatinib 12 mg orally once daily on a 21 or 42 day cycle. It is taken 0-4 hours after completion of pembrolizumabd administration in the clinic on cycle 1 day 1(C1D1), C2D1, C3D1, etc. Taken at home on all other days.
  • Drug: Lenvatinib
    Oral capsules
Experimental
Lenvatinib 8 mg 		Participants with body weight (BW)<60 kg receive Lenvatinib 8 mg orally once daily on a 21 or 42 day cycle. It is taken 0-4 hours after completion of pembrolizumabd administration in the clinic on cycle 1 day 1(C1D1), C2D1, C3D1, etc. Taken at home on all other days.
  • Drug: Lenvatinib
    Oral capsules
Experimental
Lenvatinib 2mg 		Participants with body weight (BW)<60 kg receive Lenvatinib 2 mg orally once daily on a 21 or 42 day cycle. It is taken 0-4 hours after completion of pembrolizumab administration in the clinic on cycle 1 day 1(C1D1), C2D1, C3D1, etc. Taken at home on all other days.
  • Drug: Lenvatinib
    Oral capsules
Experimental
Olaparib 300mg 		Participants receive Olaparib 300 mg orally twice daily (BID) until disease progression or toxicity prohibits its administration.
  • Drug: Olaparib
    300mg or 250mg or 100mg oral tablers
    Other names:
    • Lynparza
Experimental
Olaparib 250mg 		Participants receive Olaparib 250 mg orally twice daily (BID) until disease progression or toxicity prohibits its administration.
  • Drug: Olaparib
    300mg or 250mg or 100mg oral tablers
    Other names:
    • Lynparza
Experimental
Olaparib 100mg 		Participants receive Olaparib 100 mg orally twice daily (BID) until disease progression or toxicity prohibits its administration.
  • Drug: Olaparib
    300mg or 250mg or 100mg oral tablers
    Other names:
    • Lynparza
Experimental
MK-4280 800mg 		Participants receive MK-4280 800mg as IV infusion every 3 weeks (Q3W) and may continue study therapy until study treatment completion or may transition to pembrolizumab to complete their treatment.
  • Drug: MK-4280
    IV Infusion
    Other names:
    • Favezelimab
Experimental
MK-4280A 		Participants receive MK-4280A (800mg favezelimab + 200mg pembrolizumab) as IV infusion every 3 weeks (Q3W) and may continue study therapy until study treatment completion or may transition to pembrolizumab to complete their treatment.
  • Biological: MK-4280A
    800mg favezelimab + 200mg pembrolizumab IV Infusion
Experimental
Pembrolizumab (+) Berahyaluronidase alfa 395 mg 		Participants receive 395 mg of a fixed-dose formulation of pembrolizumab and berahyaluronidase alfa via subcutaneous (SC) administration on Day 1 of each 3-week cycle for up to 35 administrations.
  • Biological: Pembrolizumab (+) Berahyaluronidase alfa
    395 mg or 790 mg SC administration
    Other names:
    • MK-3475A
Experimental
Pembrolizumab (+) Berahyaluronidase alfa 790 mg 		Participants receive 790 mg of a fixed-dose formulation of pembrolizumab and berahyaluronidase alfa via SC administration on Day 1 of each 6-week cycle for up to 35 administrations.
  • Biological: Pembrolizumab (+) Berahyaluronidase alfa
    395 mg or 790 mg SC administration
    Other names:
    • MK-3475A

Recruiting Locations

Arizona Cancer Center at UMC North ( Site 0018)
Tucson, Arizona 85719
Contact:
Study Coordinator
520-694-1053

Comprehensive Blood & Cancer Center [Bakersfield, CA] ( Site 0054)
Bakersfield, California 93309
Contact:
Study Coordinator
661-322-2206

UCLA Hematology/Oncology - Westwood (Building 100) ( Site 0009)
Los Angeles, California 90095
Contact:
Study Coordinator
310-794-6913

Stanford Cancer Center ( Site 0086)
Palo Alto, California 94304
Contact:
Study Coordinator
650-721-7489

UCSF Helen Diller Family Comprehensive Cancer Center ( Site 0004)
San Francisco, California 94158
Contact:
Study Coordinator
415-514-6382

Providence Saint John's Health Center ( Site 0059)
Santa Monica, California 90404
Contact:
Study Coordinator
310-449-5244

University of Colorado Cancer Center ( Site 0021)
Aurora, Colorado 80045
Contact:
Study Coordinator
720-848-7135

Holy Cross Hospital, Michael & Dianne Bienes Comp Cancer Ctr ( Site 0022)
Fort Lauderdale, Florida 33308
Contact:
Study Coordinator
954-776-3036

Mount Sinai Braman Comprehensive Cancer Center ( Site 0031)
Miami Beach, Florida 33140
Contact:
Study Coordinator
305-674-2625

Augusta University ( Site 0077)
Augusta, Georgia 30912
Contact:
Study Coordinator
706-721-5557

Northwest Georgia Oncology Centers PC ( Site 0061)
Marietta, Georgia 30060
Contact:
Study Coordinator
770-281-5124

The University of Chicago ( Site 0020)
Chicago, Illinois 60637
Contact:
Study Coordinator
773-834-7961

University of Iowa Hospital and Clinics ( Site 0026)
Iowa City, Iowa 52242
Contact:
Study Coordinator
319-356-1228

James Graham Brown Cancer Center ( Site 0058)
Louisville, Kentucky 40202
Contact:
Study Coordinator
502-562-4673

Mercy Health-Paducah Cancer Center ( Site 0084)
Paducah, Kentucky 42003
Contact:
Study Coordinator
270-441-4343

Women's Cancer Care ( Site 0088)
Covington, Louisiana 70433
Contact:
Study Coordinator
985-317-6005

MedStar Franklin Square Medical Center ( Site 0046)
Baltimore, Maryland 21237
Contact:
Study Coordinator
443-777-7364

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins ( Site 0056)
Baltimore, Maryland 21287
Contact:
Study Coordinator
410-955-5222

Maryland Oncology Hematology (MOH) ( Site 8000)
Columbia, Maryland 21044
Contact:
Study Coordinator
410-964-2212

Karmanos Cancer Institute ( Site 0047)
Detroit, Michigan 48201
Contact:
Study Coordinator
800-527-6266

Mayo Clinic in Rochester, Minnesota ( Site 0002)
Rochester, Minnesota 55905
Contact:
Study Coordinator
507-538-6739

Comprehensive Cancer Centers of Nevada ( Site 0043)
Las Vegas, Nevada 89169
Contact:
Study Coordinator
702-952-3400

Cancer Institute of New Jersey ( Site 0025)
New Brunswick, New Jersey 08901
Contact:
Study Coordinator
917-991-4174

Laura and Isaac Perlmutter Cancer Center at NYU Langone Health ( Site 0032)
New York, New York 10016
Contact:
Study Coordinator
212-731-5431

White Plains Hospital-Center for Cancer Care ( Site 0069)
White Plains, New York 10601
Contact:
Study Coordinator
914-849-7630

WakeMed Cancer Care - Waverly Hematology & Medical Oncology ( Site 0074)
Cary, North Carolina 27518
Contact:
Study Coordinator
919-235-2873

University of North Carolina at Chapel Hill ( Site 0040)
Chapel Hill, North Carolina 27514
Contact:
Study Coordinator
919-843-7713

Duke Cancer Center ( Site 0028)
Durham, North Carolina 27710
Contact:
Study Coordinator
919-668-3771

Oklahoma Cancer Specialists and Research Institute, LLC ( Site 0082)
Tulsa, Oklahoma 74146
Contact:
Study Coordinator
918-505-3200

St. Luke's University Health Network ( Site 0017)
Bethlehem, Pennsylvania 18015
Contact:
Study Coordinator
484-503-4153

University of Pennsylvania ( Site 0010)
Philadelphia, Pennsylvania 19104
Contact:
Study Coordinator
215-662-7908

Fox Chase Cancer Center ( Site 0042)
Philadelphia, Pennsylvania 19111
Contact:
Study Coordinator
215-214-4297

UPMC Hillman Cancer Center ( Site 0008)
Pittsburgh, Pennsylvania 15232
Contact:
Study Coordinator
412-623-3272

Saint Francis Health System ( Site 0089)
Greenville, South Carolina 29607
Contact:
Study Coordinator
864-603-6300

Vanderbilt Health One Hundred Oaks Diagnostic ( Site 0060)
Nashville, Tennessee 37204
Contact:
Study Coordinator
615-936-6726

Vanderbilt Ingram Cancer Center ( Site 0015)
Nashville, Tennessee 37232
Contact:
Study Coordinator
615-936-6726

Texas Oncology - Central/South Texas ( Site 8001)
Austin, Texas 78745
Contact:
Study Coordinator
512-447-2202

Texas Oncology-Baylor Sammons Cancer Center ( Site 0062)
Dallas, Texas 75246
Contact:
Study Coordinator
214-370-1000

University of Texas MD Anderson Cancer Center ( Site 0007)
Houston, Texas 77030
Contact:
Study Coordinator
713-792-2921

South Texas Accelerated Research Therapeutics, LLC (START) ( Site 0001)
San Antonio, Texas 78229
Contact:
Study Coordinator
210-593-5265

University of Virginia Health System ( Site 0035)
Charlottesville, Virginia 22908
Contact:
Study Coordinator
434-243-6303

VCU Health Adult Outpatient Pavillion ( Site 0080)
Richmond, Virginia 23219
Contact:
Study Coordinator
804-628-6430

Blue Ridge Cancer Care ( Site 0067)
Roanoke, Virginia 24014
Contact:
Study Coordinator
540-491-2244

Fred Hutchinson Cancer Center ( Site 0024)
Seattle, Washington 98109
Contact:
Study Coordinator
206-606-8245

More Details

Status
Recruiting
Sponsor
Merck Sharp & Dohme LLC

Study Contact

Toll Free Number
1-888-577-8839
Trialsites@msd.com