Recruiting
Phase 3
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)
Condition(s) studied
Solid TumorsHematologic Malignancies
Investigational drug(s) / intervention(s)
PembrolizumabStandard of Care (SOC)LenvatinibOlaparibMK-4280MK-4280APembrolizumab (+) Berahyaluronidase alfa
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
Study 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.
Eligibility
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.
Primary outcome measure(s)
- Overall Survival (OS) — 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 known to be alive.
Trial sites (782)
| Facility | City | Region | Status |
| Arizona Cancer Center at UMC North ( Site 0018) |
Tucson |
Arizona |
Recruiting |
| Comprehensive Blood & Cancer Center [Bakersfield, CA] ( Site 0054) |
Bakersfield |
California |
Recruiting |
| California Cancer Associates for Research & Excellence ( Site 0016) |
Fresno |
California |
Completed |
| Providence Medical Foundation ( Site 0087) |
Fullerton |
California |
Completed |
| The Angeles Clinic and Research Institute ( Site 0005) |
Los Angeles |
California |
Active Not Recruiting |
| UCLA - Hematology/Oncology - Administrative Office ( Site 0009) |
Los Angeles |
California |
Recruiting |
| University of California, Irvine (UCI) Health - UC Irvine Medical Center ( Site 0076) |
Orange |
California |
Completed |
| Stanford Cancer Center ( Site 0086) |
Palo Alto |
California |
Recruiting |
| UCSF Helen Diller Family Comprehensive Cancer Center ( Site 0004) |
San Francisco |
California |
Recruiting |
| Providence Saint John's Health Center ( Site 0059) |
Santa Monica |
California |
Recruiting |
| University of Colorado Cancer Center ( Site 0021) |
Aurora |
Colorado |
Recruiting |
| Yale Cancer Center ( Site 0014) |
New Haven |
Connecticut |
Completed |
| Georgetown University Medical Center ( Site 0023) |
Washington D.C. |
District of Columbia |
Active Not Recruiting |
| Holy Cross Hospital, Michael & Dianne Bienes Comp Cancer Ctr ( Site 0022) |
Fort Lauderdale |
Florida |
Recruiting |
| Baptist MD Anderson Cancer Center ( Site 0083) |
Jacksonville |
Florida |
Completed |
| Mount Sinai Braman Comprehensive Cancer Center ( Site 0031) |
Miami Beach |
Florida |
Recruiting |
| Moffitt Cancer Center ( Site 0011) |
Tampa |
Florida |
Completed |
| Emory School of Medicine ( Site 0013) |
Atlanta |
Georgia |
Completed |
| Augusta University ( Site 0077) |
Augusta |
Georgia |
Recruiting |
| Northwest Georgia Oncology Centers PC ( Site 0061) |
Marietta |
Georgia |
Recruiting |
| Kaiser Permanente Moanalua Medical Center ( Site 0063) |
Honolulu |
Hawaii |
Completed |
| The University of Chicago ( Site 0020) |
Chicago |
Illinois |
Recruiting |
| University of Iowa Hospital and Clinics ( Site 0026) |
Iowa City |
Iowa |
Recruiting |
| James Graham Brown Cancer Center ( Site 0058) |
Louisville |
Kentucky |
Recruiting |
| Mercy Health-Paducah Cancer Center ( Site 0084) |
Paducah |
Kentucky |
Recruiting |
| Women's Cancer Care ( Site 0088) |
Covington |
Louisiana |
Recruiting |
| MedStar Franklin Square Medical Center ( Site 0046) |
Baltimore |
Maryland |
Recruiting |
| Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins ( Site 0056) |
Baltimore |
Maryland |
Recruiting |
| Maryland Oncology Hematology (MOH) ( Site 8000) |
Columbia |
Maryland |
Recruiting |
| Massachusetts General Hospital ( Site 0041) |
Boston |
Massachusetts |
Active Not Recruiting |
| Dana-Farber Cancer Institute ( Site 0006) |
Boston |
Massachusetts |
Active Not Recruiting |
| Karmanos Cancer Institute ( Site 0047) |
Detroit |
Michigan |
Recruiting |
| Mayo Clinic in Rochester, Minnesota ( Site 0002) |
Rochester |
Minnesota |
Active Not Recruiting |
| Comprehensive Cancer Centers of Nevada ( Site 0043) |
Las Vegas |
Nevada |
Recruiting |
| John Theurer Cancer Center at Hackensack University Medical Center ( Site 0038) |
Hackensack |
New Jersey |
Active Not Recruiting |
| Cancer Institute of New Jersey ( Site 0025) |
New Brunswick |
New Jersey |
Recruiting |
| Laura and Isaac Perlmutter Cancer Center at NYU Langone Health ( Site 0032) |
New York |
New York |
Recruiting |
| Memorial Sloan Kettering Cancer Center ( Site 0012) |
New York |
New York |
Completed |
| White Plains Hospital-Center for Cancer Care ( Site 0069) |
White Plains |
New York |
Recruiting |
| WakeMed Cancer Care - Waverly Hematology & Medical Oncology ( Site 0074) |
Cary |
North Carolina |
Recruiting |
+ 742 more sites — see the full list on the official registry below.
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