Efficacy and Safety of Pembrolizumab (MK-3475) Plus Lenvatinib (E7080/MK-7902) in Previously Treated Participants With Select Solid Tumors (MK-7902-005/E7080-G000-224/LEAP-005)

Program Status

Completed

Phase

Phase 2

Prior Immunotherapy Allowed

No

CRC-directed Trial

Yes

Drugs

Lenvatinib, Pembrolizumab, Keytruda, Lenvima

Tags

MSS/ MMRp

Comments

Lenvatinib (E7080) is a multi-targeted Tyrosine Kinase Inhibitor: targets receptor tyrosine kinases, including vascular endothelial growth factor receptor 1 and 2 (VEGFR1/2), fibroblast growth factor receptor 1, platelet‑derived growth factor receptor β and v‑kit Hardy‑Zuckerman 4 feline sarcoma viral oncogene homolog.
Pembrolizumab is an anti PD-1, checkpoint inhibitor immunotherapy.

Patients need to have received 2 prior lines of therapy
No prior exposure to study drugs or other anti PD-1 inhibitors, anti-CTLA4, OX40, is allowed.

Location Location Status
United States
City of Hope ( Site 0002)
Duarte, California 91010
Completed
Cedars Sinai Medical Center ( Site 0003)
Los Angeles, California 90048
Completed
University of California Davis Comprehensive Cancer Center ( Site 0005)
Sacramento, California 95817
Completed
University of Colorado, Anschutz Cancer Pavilion ( Site 0007)
Aurora, Colorado 80045
Completed
University of Florida-Health Cancer Center-Orlando ( Site 0015)
Orlando, Florida 32806
Completed
Rutgers Cancer Institute of New Jersey ( Site 0009)
New Brunswick, New Jersey 08901
Completed
Laura and Isaac Perlmutter Cancer Center at NYU Langone Health ( Site 0023)
New York, New York 10016
Completed
Sanford Fargo Medical Center ( Site 0059)
Fargo, North Dakota 58102
Completed
Lehigh Valley Hospital- Cedar Crest ( Site 0047)
Allentown, Pennsylvania 18103
Completed
Sanford Cancer Center ( Site 0058)
Sioux Falls, South Dakota 57104
Completed
West Cancer Center - East Campus ( Site 0018)
Germantown, Tennessee 38138
Completed
Mary Crowley Cancer Research Centers - Medical City Hospital ( Site 0049)
Dallas, Texas 75230
Completed
Swedish Medical Center ( Site 0021)
Seattle, Washington 98104
Completed
University of Wisconsin Carbone Cancer Center ( Site 0017)
Madison, Wisconsin 53792-0001
Completed
Argentina
Fundacion Favaloro para la Docencia e Investigacion Medica ( Site 2106)
Ciudad Autonoma de Buenos Aires, Buenos Aires C1078AAI
Completed
Hospital Aleman ( Site 2100)
Buenos Aires, Caba 1118
Completed
Hospital Britanico de Buenos Aires ( Site 2109)
Ciudad de Buenos Aires, Caba C1280AEB
Completed
Instituto de Oncologia de Rosario ( Site 2105)
Rosario, Santa Fe S2000KZE
Completed
CEMIC ( Site 2104)
Buenos Aires C1431FWO
Completed
IDIM Instituto de Diagnostico e Investigaciones Metabolicas ( Site 2101)
Caba C1012AAR
Completed
Australia
Royal Brisbane and Women s Hospital ( Site 0901)
Herston, Queensland 4029
Completed
Alfred Health ( Site 0902)
Melbourne, Victoria 3004
Completed
Sir Charles Gairdner Hospital ( Site 0903)
Nedlands, Western Australia 6009
Completed
Canada
BC Cancer - Abbotsford ( Site 0200)
Abbotsford, British Columbia V2S 0C2
Completed
CancerCare Manitoba ( Site 0201)
Winnipeg, Manitoba R3E 0V9
Completed
Hamilton Health Sciences-Juravinski Cancer Centre ( Site 0208)
Hamilton, Ontario L8V 4X2
Completed
Sunnybrook Research Institute ( Site 0207)
Toronto, Ontario M4N 3M5
Completed
Princess Margaret Cancer Centre ( Site 0202)
Toronto, Ontario M5G 2M9
Completed
Centre Hospitalier de l Universite de Montreal - CHUM ( Site 0210)
Montreal, Quebec H2X 3E4
Completed
CHU de Quebec Universite de Laval ( Site 0206)
Quebec G1R 2J6
Completed
Chile
Centro Investigación del Cáncer James Lind ( Site 1203)
Temuco, Araucania 4780000
Completed
Fundacion Arturo Lopez Perez ( Site 1201)
Santiago, Region M. De Santiago 7500921
Completed
Pontificia Universidad Catolica de Chile ( Site 1202)
Santiago, Region M. De Santiago 8330024
Completed
Hospital Clinico Universidad de Chile ( Site 1200)
Santiago, Region M. De Santiago 8380456
Completed
Colombia
Fundacion Colombiana de Cancerologia Clinica Vida ( Site 1105)
Medellin, Antioquia 050030
Completed
Instituto Nacional de Cancerologia E.S.E ( Site 1102)
Bogota, Distrito Capital De Bogota 110321
Completed
Oncologos del Occidente S.A. ( Site 1106)
Pereira, Risaralda 660001
Completed
Fundacion Valle del Lili ( Site 1101)
Cali, Valle Del Cauca 760032
Completed
France
Centre Antoine Lacassagne ( Site 0404)
Nice, Alpes-Maritimes 06189
Completed
Centre Leon Berard ( Site 0405)
Lyon, Auvergne 69373
Completed
Institut Claudius Regaud IUCT Oncopole ( Site 0403)
Toulouse, Haute-Garonne 31059
Completed
Centre Oscar Lambret ( Site 0401)
Lille, Nord 59000
Completed
Institut de Cancerologie de l Ouest Centre Rene Gauducheau ( Site 0402)
Saint-Herblain, Val-de-Marne 44805
Completed
Institut Gustave Roussy ( Site 0400)
Villejuif, Val-de-Marne 94800
Completed
Germany
Robert Bosch GmbH ( Site 0307)
Stuttgart, Baden-Wurttemberg 70376
Completed
Universitaetsklinikum Regensburg ( Site 0304)
Regensburg, Bayern 93053
Completed
Universitaetsklinikum Frankfurt ( Site 0306)
Frankfurt am Main, Hessen 60528
Completed
HELIOS Dr. Horst Schmidt Kliniken Wiesbaden ( Site 0301)
Wiesbaden, Hessen 65199
Completed
SRH Wald-Klinikum Gera GmbH ( Site 0309)
Gera, Thuringen 07548
Completed
Universitaetsklinikum Jena ( Site 0302)
Jena, Thuringen 07740
Completed
Israel
Soroka Medical Center ( Site 0601)
Beer Sheva 8457108
Completed
Rambam Medical Center ( Site 0602)
Haifa 3109601
Completed
Hadassah Ein Kerem Medical Center ( Site 0604)
Jerusalem 9112001
Completed
Chaim Sheba Medical Center ( Site 0600)
Ramat Gan 5262000
Completed
Sourasky Medical Center ( Site 0603)
Tel Aviv 6423906
Completed
Italy
Istituto Clinico Humanitas Research Hospital ( Site 1402)
Rozzano, Milano
Completed
Policlinico Le Scotte - A.O. Senese ( Site 1401)
Siena, Toscana 53100
Completed
Istituto Nazionale Tumori Fondazione Pascale ( Site 1400)
Napoli 80131
Completed
Fondazione Policlinico Universitario A. Gemelli ( Site 1403)
Roma 00168
Completed
Korea, Republic of
Asan Medical Center ( Site 1002)
Songpagu, Seoul 05505
Completed
Seoul National University Hospital ( Site 1000)
Seoul 03080
Completed
Severance Hospital Yonsei University Health System ( Site 1001)
Seoul 03722
Completed
Russian Federation
Arkhangelsk Clinical Oncological Dispensary ( Site 1600)
Arkhangelsk, Arkhangel Skaya Oblast 163045
Completed
Russian Oncological Research Center n.a. N.N. Blokhin ( Site 1604)
Moscow, Moskva 115478
Completed
Leningrad Regional Oncology Center ( Site 1609)
Saint-Petersburg, Sankt-Peterburg 188663
Completed
Scientific Research Oncology Institute n.a. N.N.Petrov ( Site 1610)
Saint-Petersburg, Sankt-Peterburg 197758
Completed
City Clinical Oncology Center ( Site 1608)
Saint-Petersburg, Sankt-Peterburg 198255
Completed
Republican Clinical Oncology Dispensary of Tatarstan MoH ( Site 1603)
Kazan, Tatarstan, Respublika 420029
Completed
Spain
Hospital Clinic i Provincial ( Site 0703)
Barcelona 08036
Completed
Hospital Universitario Gregorio Maranon ( Site 0701)
Madrid 28009
Completed
Clinica Universitaria de Navarra ( Site 0704)
Madrid 28027
Completed
Hospital Ramon y Cajal ( Site 0702)
Madrid 28034
Completed
Switzerland
Inselspital Universitaetsspital Bern ( Site 1705)
Bern, Berne 3010
Completed
Kantonsspital Graubuenden ( Site 1704)
Chur, Grisons 7000
Completed
Kantonsspital St. Gallen ( Site 1702)
St. Gallen, Sankt Gallen 9007
Completed
Ospedale Regionale di Bellinzona e Valli ( Site 1703)
Bellinzona, Ticino 6500
Completed
Hopitaux Universitaires de Geneve HUG ( Site 1701)
Geneve 1211
Completed
Universitaetsspital Zurich ( Site 1700)
Zurich 8091
Completed
Taiwan
National Cheng Kung University Hospital ( Site 3003)
Tainan 704
Completed
National Taiwan University Hospital ( Site 3000)
Taipei 10002
Completed
Thailand
Chulalongkorn University ( Site 5001)
Bangkok, Krung Thep Maha Nakhon 10330
Completed
Ramathibodi Hospital. ( Site 5002)
Bangkok, Krung Thep Maha Nakhon 10400
Completed
Siriraj Hospital ( Site 5003)
Bangkok, Krung Thep Maha Nakhon 10700
Completed
United Kingdom
Cambridge University Hospitals NHS Trust ( Site 0803)
Cambridge, Cambridgeshire CB2 0QQ
Completed
Leicester Royal Infirmary. Univ. Hosp. of Leicester NHS Trust ( Site 0804)
Leicester, Leicestershire LE1 5WW
Completed
Guy's Hospital ( Site 0806)
London, London, City Of SE1 9RT
Completed
Royal Marsden Hospital (Sutton) ( Site 0800)
London, Surrey SM3 5PT
Completed
Christie NHS Foundation Trust ( Site 0805)
Manchester M20 4BX
Completed

Inclusion Criteria

Inclusion Criteria:

* Has a histologically or cytologically-documented, advanced (metastatic and/or unresectable) solid tumor that is incurable and for which prior standard systemic therapy has failed in one of the following cohorts: TNBC, Ovarian Cancer, Gastric Cancer, Colorectal Cancer, GBM, BTC (intrahepatic, extrahepatic cholangiocarcinoma and gall bladder cancer; excludes Ampulla of Vater), Pancreatic Cancer
* Must have progressed on or since the last treatment
* Has measurable disease per RECIST 1.1 (RANO for the GBM cohort) as assessed by the local site investigator/radiology and confirmed by BICR
* Has provided a PD-L1 evaluable archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated
* Male participants agree to use approved contraception during the treatment period for at least 7 days after the last dose of lenvatinib, or refrain from heterosexual intercourse during this period
* Female participants are not pregnant or breastfeeding, and are not a woman of childbearing potential (WOCBP), OR are a WOCBP that agrees to use contraception during the treatment period (or 14 days prior to the initiation of study treatment for oral contraception) and for at least 120 days post pembrolizumab, or 30 days post lenvatinib, whichever occurs last
* Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 within 3 days of study treatment initiation
* Has adequate organ function

For Triple Negative Breast Cancer Participants:

* Has received one or 2 prior lines of therapy
* Has Lactate Dehydrogenase (LDH) <2.0 x Upper Limit of Normal (ULN)
* Has locally determined results for estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 tumor analyses

For Ovarian Cancer Participants:

- Has primary ovarian cancer and has received 3 prior lines of therapy.

For Gastric Cancer Participants:

- Has received 2 prior lines of therapy. Note: Gastric cancer will include participants with both gastric and gastroesophageal junction (GEJ) adenocarcinoma. Participants with squamous cell carcinoma histology are not eligible

For Colorectal Cancer Participants:

- Has received 2 prior lines of therapy

For GBM Participants:

* Has failed initial systemic therapy for newly diagnosed GBM
* Have the following time periods elapsed before the projected start of scheduled study treatment: 1) at least 3 weeks from prior surgical resection, 2) at least 1 week from stereotactic biopsy, 3) at least 6 months from completion of prior radiotherapy, 4) at least 4 weeks (or 5 half-lives, whichever is shorter) from any investigational agent, 5) at least 4 weeks from cytotoxic therapy, 6) at least 6 weeks from antibodies, 7) at least 4 weeks (or 5 half-lives, whichever is shorter) from other antitumor therapies and 1 week for cancer vaccines
* Be neurologically stable (e.g. without a progression of neurologic symptoms or requiring escalating doses of systemic steroid therapy within last 2 weeks) and clinically stable
* Has histologically confirmed World Health Organization (WHO) Grade IV GBM
* Has locally determined result for O^6-methylguanine-DNA methyltransferase (MGMT) analysis

For Biliary Tract Cancer Participants:

* Has received 1 prior line of therapy
* Child-Pugh Score, Class A: well-compensated disease. Child-Pugh Score of 5-6

For Pancreatic Cancer Participants:

* Has pathologically (histologically or cytologically) confirmed pancreatic ductal adenocarcinoma that is metastatic at enrollment
* Has received one or 2 prior lines of therapy
* Has received prior therapy with at least 1 (platinum-containing regimen or gemcitabine-containing regimen) but no more than 2 prior systemic therapies for unresectable or metastatic pancreatic cancer

Exclusion Criteria

Exclusion Criteria:

* Has gastrointestinal malabsorption or any other condition that might affect the absorption of lenvatinib
* Has present or progressive accumulation of pleural, ascitic, or pericardial fluid requiring drainage or diuretic drugs within 2 weeks prior to enrollment (applies to all cohorts except the ovarian cancer cohort)
* Has radiographic evidence of encasement or invasion of a major blood vessel or of intratumoral cavitation. Participants with portal vein invasion (Vp4), inferior vena cava, or cardiac involvement based on imaging in the BTC cohort are not eligible for enrollment
* Has clinical significant hemoptysis or tumor bleeding within 2 weeks prior to the first dose of study treatment
* Has significant cardiovascular impairment within 12 months of the first dose of study treatment, such as history of congestive heart failure greater than New York Heart Association (NYHA) Class II, unstable angina, myocardial infarction or cerebrovascular accident (CVA), or cardiac arrhythmia associated with hemodynamic instability
* Has a history of arterial thromboembolism within 12 months of start of study treatment
* Has a known additional malignancy that is progressing or has required active treatment within the past 3 years.
* Has a serious nonhealing wound, ulcer or bone fracture
* Has had major surgery within 3 weeks prior to first dose of study interventions
* Has biologic response modifiers therapy (e.g. granulocyte colony-stimulating factor) within 4 weeks before study entry
* Has preexisting ≥Grade 3 gastrointestinal (GI) or non-gastrointestinal fistula
* Has received prior therapy with lenvatinib, an anti-PD-1, anti-PD-L1, or anti PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g. cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], Tumor necrosis factor receptor superfamily, member 4 [OX 40], tumor necrosis factor receptor superfamily member 9 [CD137])
* Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to study treatment start
* If participant received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment
* Has received prior radiotherapy within 2 weeks of start of study treatment. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-central nervous system (CNS) disease
* Has received a live vaccine within 30 days prior to the first dose of study treatment
* Has known intolerance to lenvatinib (and/or any of the excipients)
* Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study 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 the first dose of study treatment
* Has known active CNS metastases and/or carcinomatous meningitis
* Has tumors involving the brain stem
* Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients
* Has an active autoimmune disease that has required systemic treatment in past 2 years
* Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis
* Has an active infection requiring systemic therapy
* Has a known history of human immunodeficiency virus (HIV) infection
* Has a known history of hepatitis B or known active hepatitis C virus infection
* Has a known history of active tuberculosis (TB; Bacillus tuberculosis)
* Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of study treatment
* Has had an allogenic tissue/solid organ transplant (large organ transplants, stem-cell transplant requiring chronic immunosuppressant therapy necessary to prevent graft rejection)

For GBM Participants:

* Has carcinomatous meningitis
* Has recurrent tumor greater than 6 cm in maximum diameter
* Has tumor primarily localized to the brainstem or spinal cord
* Has presence of multifocal tumor, diffuse leptomeningeal or extracranial disease
* Has evidence of intratumoral or peritumoral hemorrhage on baseline magnetic resonance imaging (MRI) scan other than those that are grade ≤ 1 and either post-operative or stable on at least 2 consecutive MRI scans
* Has received Optune® TTFields within 2 weeks of study intervention

NCT ID

NCT03797326

Date Trial Added

2019-01-09

Updated Date

2024-11-15