Recruiting
Phase 3

Pembrolizumab

Sponsor:

Merck Sharp & Dohme LLC

Code:

NCT03486873

Conditions

Solid Tumors

Hematologic Malignancies

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Pembrolizumab

Standard of Care (SOC)

Lenvatinib

Olaparib

MK-4280

Study Details

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 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

Study ID

NCT03486873

Start date

Aug 21, 2018

Status verified date

Sep, 2026

Completion date

Aug 4, 2043

Anticipated

Primary completion date

Aug 4, 2043

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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

Enrollment

3500 participants

Anticipated

Allocation

Non randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

experimental: Olaparib 300mg

Participants receive Olaparib 300 mg orally twice daily (BID) until disease progression or toxicity prohibits its administration.

experimental: Olaparib 250mg

Participants receive Olaparib 250 mg orally twice daily (BID) until disease progression or toxicity prohibits its administration.

experimental: Olaparib 100mg

Participants receive Olaparib 100 mg orally twice daily (BID) until disease progression or toxicity prohibits its administration.

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.

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.

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.

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.

Interventions

Pembrolizumab

200 or 400 mg IV infusion

Standard of Care (SOC)

IV infusion or oral tablets

Lenvatinib

Oral capsules

Olaparib

300mg or 250mg or 100mg oral tablers

MK-4280

IV Infusion

MK-4280A

800mg favezelimab + 200mg pembrolizumab IV Infusion

Pembrolizumab (+) Berahyaluronidase alfa

395 mg or 790 mg SC administration

Primary outcome measure

  • Overall Survival (OS) [ Time Frame: Up to approximately 10 years ]

Central Contacts and Locations

Central contacts

Toll Free Number

1-888-577-8839Trialsites@msd.com

Locations

Arizona Cancer Center at UMC North ( Site 0018)

Recruiting

Tucson, Arizona, United States, 85719

Contacts

Study Coordinator

520-694-1053

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

Recruiting

Bakersfield, California, United States, 93309

Contacts

Study Coordinator

661-322-2206

UCLA - Hematology/Oncology - Administrative Office ( Site 0009)

Recruiting

Los Angeles, California, United States, 90095

Contacts

Study Coordinator

310-794-6913

Stanford Cancer Center ( Site 0086)

Recruiting

Palo Alto, California, United States, 94304

Contacts

Study Coordinator

650-721-7489

UCSF Helen Diller Family Comprehensive Cancer Center ( Site 0004)

Recruiting

San Francisco, California, United States, 94158

Contacts

Study Coordinator

415-514-6382

Providence Saint John's Health Center ( Site 0059)

Recruiting

Santa Monica, California, United States, 90404

Contacts

Study Coordinator

310-449-5244

University of Colorado Cancer Center ( Site 0021)

Recruiting

Aurora, Colorado, United States, 80045

Contacts

Study Coordinator

720-848-7135

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

Recruiting

Fort Lauderdale, Florida, United States, 33308

Contacts

Study Coordinator

954-776-3036

Mount Sinai Braman Comprehensive Cancer Center ( Site 0031)

Recruiting

Miami Beach, Florida, United States, 33140

Contacts

Study Coordinator

305-674-2625

Augusta University ( Site 0077)

Recruiting

Augusta, Georgia, United States, 30912

Contacts

Study Coordinator

706-721-5557

Northwest Georgia Oncology Centers PC ( Site 0061)

Recruiting

Marietta, Georgia, United States, 30060

Contacts

Study Coordinator

770-281-5124

The University of Chicago ( Site 0020)

Recruiting

Chicago, Illinois, United States, 60637

Contacts

Study Coordinator

773-834-7961

University of Iowa Hospital and Clinics ( Site 0026)

Recruiting

Iowa City, Iowa, United States, 52242

Contacts

Study Coordinator

319-356-1228

James Graham Brown Cancer Center ( Site 0058)

Recruiting

Louisville, Kentucky, United States, 40202

Contacts

Study Coordinator

502-562-4673

Mercy Health-Paducah Cancer Center ( Site 0084)

Recruiting

Paducah, Kentucky, United States, 42003

Contacts

Study Coordinator

270-441-4343

Women's Cancer Care ( Site 0088)

Recruiting

Covington, Louisiana, United States, 70433

Contacts

Study Coordinator

985-317-6005

MedStar Franklin Square Medical Center ( Site 0046)

Recruiting

Baltimore, Maryland, United States, 21237

Contacts

Study Coordinator

443-777-7364

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

Recruiting

Baltimore, Maryland, United States, 21287

Contacts

Study Coordinator

410-955-5222

Maryland Oncology Hematology (MOH) ( Site 8000)

Recruiting

Columbia, Maryland, United States, 21044

Contacts

Study Coordinator

410-964-2212

Karmanos Cancer Institute ( Site 0047)

Recruiting

Detroit, Michigan, United States, 48201

Contacts

Study Coordinator

800-527-6266

Comprehensive Cancer Centers of Nevada ( Site 0043)

Recruiting

Las Vegas, Nevada, United States, 89169

Contacts

Study Coordinator

702-952-3400

Cancer Institute of New Jersey ( Site 0025)

Recruiting

New Brunswick, New Jersey, United States, 08901

Contacts

Study Coordinator

917-991-4174

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

Recruiting

New York, New York, United States, 10016

Contacts

Study Coordinator

212-731-5431

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

Recruiting

White Plains, New York, United States, 10601

Contacts

Study Coordinator

914-849-7630

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

Recruiting

Cary, North Carolina, United States, 27518

Contacts

Study Coordinator

919-235-2873

University of North Carolina at Chapel Hill ( Site 0040)

Recruiting

Chapel Hill, North Carolina, United States, 27514

Contacts

Study Coordinator

919-843-7713

Duke Cancer Center ( Site 0028)

Recruiting

Durham, North Carolina, United States, 27710

Contacts

Study Coordinator

919-668-3771

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

Recruiting

Tulsa, Oklahoma, United States, 74146

Contacts

Study Coordinator

918-505-3200

University of Pennsylvania ( Site 0010)

Recruiting

Philadelphia, Pennsylvania, United States, 19104

Contacts

Study Coordinator

215-662-7908

Fox Chase Cancer Center ( Site 0042)

Recruiting

Philadelphia, Pennsylvania, United States, 19111

Contacts

Study Coordinator

215-214-4297

UPMC Hillman Cancer Center ( Site 0008)

Recruiting

Pittsburgh, Pennsylvania, United States, 15232

Contacts

Study Coordinator

412-623-3272

Vanderbilt Health One Hundred Oaks Diagnostic ( Site 0060)

Recruiting

Nashville, Tennessee, United States, 37204

Contacts

Study Coordinator

615-936-6726

Vanderbilt University Medical Center-Vanderbilt-Ingram Cancer Center ( Site 0015)

Recruiting

Nashville, Tennessee, United States, 37232

Contacts

Study Coordinator

615-936-6726

Texas Oncology - Central/South Texas ( Site 8001)

Recruiting

Austin, Texas, United States, 78745

Contacts

Study Coordinator

512-447-2202

Texas Oncology-Baylor Sammons Cancer Center ( Site 0062)

Recruiting

Dallas, Texas, United States, 75246

Contacts

Study Coordinator

214-370-1000

University of Texas MD Anderson Cancer Center ( Site 0007)

Recruiting

Houston, Texas, United States, 77030

Contacts

Study Coordinator

713-792-2921

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

Recruiting

San Antonio, Texas, United States, 78229

Contacts

Study Coordinator

210-593-5265

University of Virginia Health System ( Site 0035)

Recruiting

Charlottesville, Virginia, United States, 22908

Contacts

Study Coordinator

434-243-6303

VCU Health Adult Outpatient Pavillion ( Site 0080)

Recruiting

Richmond, Virginia, United States, 23219

Contacts

Study Coordinator

804-628-6430

Blue Ridge Cancer Care ( Site 0067)

Recruiting

Roanoke, Virginia, United States, 24014

Contacts

Study Coordinator

540-491-2244

Fred Hutchinson Cancer Center ( Site 0024)

Recruiting

Bellevue, Washington, United States, 98004

Contacts

Study Coordinator

206-606-8245

Arthur J.E. Child Comprehensive Cancer Centre ( Site 2815)

Recruiting

Calgary, Alberta, Canada, T2N 5G2

Contacts

Study Coordinator

(587) 231-6204

Cross Cancer Institute ( Site 2804)

Recruiting

Edmonton, Alberta, Canada, T6G 1Z2

Contacts

Study Coordinator

7804328248

CancerCare Manitoba ( Site 2814)

Recruiting

Winnipeg, Manitoba, Canada, R3E 0V9

Contacts

Study Coordinator

204-787-2197

Kingston Health Sciences Centre-Kingston General Hospital Site ( Site 2808)

Recruiting

Kingston, Ontario, Canada, K7L 2V7

Contacts

Study Coordinator

6135496666

The Ottawa Hospital - General Campus ( Site 2813)

Recruiting

Ottawa, Ontario, Canada, K1H 8L6

Contacts

Study Coordinator

613-737-7700x71985

Sunnybrook Research Institute ( Site 2802)

Recruiting

Toronto, Ontario, Canada, M4N 3M5

Contacts

Study Coordinator

4164804616

Mount Sinai Hospital ( Site 2811)

Recruiting

Toronto, Ontario, Canada, M5G 1X5

Contacts

Study Coordinator

416-586-5117

Princess Margaret Cancer Centre ( Site 2803)

Recruiting

Toronto, Ontario, Canada, M5G 2C4

Contacts

Study Coordinator

4169462000

Centre Intégré de Santé et de Services Sociaux de la Montérégie-Centre-Oncology ( Site 2809)

Recruiting

Greenfield Park, Quebec, Canada, J4V 2H1

Contacts

Study Coordinator

4504665000

Centre Intégré de Santé et de Services Sociaux (CISSS) de La-Centre intégré de cancérologie de Lava ( Site 2810)

Recruiting

Laval, Quebec, Canada, H7M 3L9

Contacts

Study Coordinator

450-668-1010x23671

Centre Hospitalier de l Universite de Montreal - CHUM ( Site 2807)

Recruiting

Montreal, Quebec, Canada, H2X 3E4

Contacts

Study Coordinator

5144127512

Jewish General Hospital ( Site 2800)

Recruiting

Montreal, Quebec, Canada, H3T 1E2

Contacts

Study Coordinator

5143408222

St. Marys Hospital Center ( Site 2820)

Recruiting

Montreal, Quebec, Canada, H3T 1M5

Contacts

Study Coordinator

514-345-3511x3378

McGill University Health Centre ( Site 2818)

Recruiting

Montreal, Quebec, Canada, H4A 3J1

Contacts

Study Coordinator

5149341934

Centre intégré de cancérologie du CHU de Québec Université Laval, Hôpital de l'Enfant-Jésus ( Site 2805)

Recruiting

Québec, Quebec, Canada, G1J 1Z4

Contacts

Study Coordinator

4185254444

Centre intégré universitaire de santé et de services sociaux de l'Estrie - Centre Hospitalier Univer ( Site 2812)

Recruiting

Sherbrooke, Quebec, Canada, J1H 5H4

Contacts

Study Coordinator

8193461110X12848

Centre integre universitaire de sante et de services sociaux de la Mauricie-et-du-centre-du-quebec ( Site 2816)

Recruiting

Trois-Rivières, Quebec, Canada, G8Z 3R9

Contacts

Study Coordinator

8196973333x63238

More Information

Sponsor

Merck Sharp & Dohme LLC

Last update posted

Sep 3, 2026

Last verified

Sep, 2026

Keywords

  • PD1
  • PD-1
  • PDL1
  • PD-L1

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-08. This information was provided to ClinicalTrials.gov by Merck Sharp & Dohme LLC on 2026-09-03.