Clinical trial NCT03517449: Lenvatinib in Combination With Pembrolizumab Versus Treatment of Physician's Choice in Participants With Advanced Endometrial Cancer (MK-3475-775/E7080-G000-309 Per Merck Standard Convention [KEYNOTE-775])
Official title: A Multicenter, Open-label, Randomized, Phase 3 Trial to Compare the Efficacy and Safety of Lenvatinib in Combination With Pembrolizumab Versus Treatment of Physician's Choice in Participants With Advanced Endometrial Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Endometrial Neoplasms
Keywords: programmed cell death 1 (PD-1, PD1)
programmed cell death ligand 1 (PD-L1, PDL1)
programmed cell death ligand 2 (PD-L2, PDL2)
vascular endothelial growth factor (VEGF) receptors
lenvatinib
pembrolizumab
doxorubicin
paclitaxel
phase 3 endometrial cancer
Lead sponsor: Eisai Inc.
Sponsor class: INDUSTRY
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2018-05-07
Enrollment: 827
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a study of pembrolizumab (MK-3475, KEYTRUDA®) in combination with lenvatinib (E7080) versus treatment of physician's choice (doxorubicin or paclitaxel) for the treatment of advanced endometrial cancer. Participants will be randomly assigned to receive either pembrolizumab and lenvatinib or treatment of physician's choice. The primary study hypothesis is that pembrolizumab in combination with lenvatinib prolongs progression free survival (PFS) and overall survival (OS) when compared to treatment of physician's choice.


Eligibility criteria: Inclusion Criteria:

1. Has a histologically confirmed diagnosis of endometrial carcinoma (EC)
2. Documented evidence of advanced, recurrent or metastatic EC.
3. Has radiographic evidence of disease progression after 1 prior systemic, platinum-based chemotherapy regimen for EC. Participants may have received up to 1 additional line of platinum-based chemotherapy if given in the neoadjuvant or adjuvant treatment setting.

   Note: There is no restriction regarding prior hormonal therapy.
4. Has historical or fresh tumor biopsy specimen for determination of mismatch repair (MMR) status.
5. Has at least 1 measurable target lesion according to Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 and confirmed by Blinded Independent Central Review BICR.
6. Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 7 days of starting study treatment.
7. Is not pregnant, breastfeeding, and agrees to use a highly effective method of contraception during the treatment period and for at least 120 days (for participants treated with lenvatinib plus pembrolizumab) or at least 180 days (for participants treated with treatment of physician's choice \[TPC\]) after the last dose of study treatment.

Exclusion Criteria:

1. Has carcinosarcoma (malignant mixed mullerian tumor), endometrial leiomyosarcoma and endometrial stromal sarcomas.
2. Has unstable central nervous system (CNS) metastases.
3. Has active malignancy (except for endometrial cancer, definitively treated in-situ carcinomas \[e.g. breast, cervix, bladder\], or basal or squamous cell carcinoma of the skin) within 24 months of study start.
4. Has gastrointestinal malabsorption, gastrointestinal anastomosis, or any other condition that might affect the absorption of lenvatinib.
5. Has a pre-existing greater than or equal (\>=) Grade 3 gastrointestinal or non-gastrointestinal fistula.
6. Has radiographic evidence of major blood vessel invasion/infiltration.
7. Has clinically significant hemoptysis or tumor bleeding within 2 weeks prior to the first dose of study treatment.
8. Has a history of congestive heart failure greater than New York Heart Association (NYHA) Class II, unstable angina, myocardial infarction, cerebrovascular accident (CVA) stroke, or cardiac arrhythmia associated with hemodynamic instability within 12 months of the first dose of study treatment.
9. Has an active infection requiring systemic treatment.
10. Has not recovered adequately from any toxicity and/or complications from major surgery prior to starting therapy.
11. Is positive for Human Immunodeficiency Virus (HIV).
12. Has active Hepatitis B or C.
13. Has a history of (non-infectious) pneumonitis that required treatment with steroids, or has current pneumonitis.
14. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study.
15. 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 study start -Has an active autoimmune disease (with the exception of psoriasis) that has required systemic treatment in the past 2 years.
16. Is pregnant or breastfeeding.
17. Has had an allogenic tissue/solid organ transplant.
18. Has received \>1 prior systemic chemotherapy regimen (other than adjuvant or neoadjuvant) for Endometrial Cancer. Participants may receive up to 2 regimens of platinum-based chemotherapy in total, as long as one is given in the neoadjuvant or adjuvant treatment setting.
19. Has received prior anticancer treatment within 28 days of study start. All acute toxicities related to prior treatments must be resolved to Grade ≤1, except for alopecia and Grade ≤2 peripheral neuropathy.
20. Has received prior treatment with any treatment targeting VEGF-directed angiogenesis, any anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
21. Has received prior treatment with an agent directed to a stimulatory or co-inhibitory T-cell receptor other than an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent, and who has discontinued from that treatment due to a Grade 3 or higher immune-related adverse event.
22. Has received prior radiation therapy within 21 days of study start with the exception of palliative radiotherapy to bone lesions, which is allowed if completed 2 weeks of study start. Participants must have recovered from all radiation-related toxicities and/or complications prior to randomization.
23. Has received a live vaccine within 30 days of study start.
24. Has a known intolerance to study treatment (or any of the excipients).
25. Prior enrollment on a clinical study evaluating pembrolizumab and lenvatinib for endometrial carcinoma, regardless of treatment received.
26. Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks of study start.
27. Participants with urine protein ≥1 gram (g)/24 hour.
28. Prolongation of corrected QT (QTc) interval to \>480 milliseconds (ms).
29. Left ventricular ejection fraction (LVEF) below the institutional normal range as determined by multigated acquisition scan (MUGA) or echocardiogram (ECHO).

Primary outcomes:
measure: Progression-free Survival (PFS)
timeFrame: From the date of randomization to the date of the first documentation of disease progression or death, whichever occurred first or up to data cutoff date 26 October 2020 (up to approximately 2 years 5 months)
measure: Overall Survival (OS)
timeFrame: From the date of randomization until the date of death from any cause or up to data cutoff date 26 October 2020 (up to approximately 2 years 5 months)
Secondary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: From date of randomization up to first documentation of PD or date of death, whichever occurred first up to data cutoff date 26 October 2020 (up to approximately 2 years 5 months)
measure: Health-Related Quality of Life (HRQoL) Assessed by European Organisation for the Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire C30 (QLQC30) Score
timeFrame: At baseline (prior to first dose of study drug), on Day 1 of each subsequent cycle (cycle length of either 21 or 28 days), and at the post-treatment visit (up to 5 years and 5 months)
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Immune-Related Adverse Events (irAEs)
timeFrame: From the first dose of study drug up to data cutoff date 26 October 2020 (up to approximately 2 years 5 months)
measure: Percentage of Participants Discontinued Study Treatment Due to TEAEs
timeFrame: From the first dose of study drug up to data cutoff date 26 October 2020 (up to approximately 2 years 5 months)
measure: Time to Treatment Failure Due to Toxicity
timeFrame: From the date of randomization to the date of discontinuation of study treatment due to TEAEs (up to 5 years 5 months)
measure: Model Predicted Apparent Total Clearance (CL/F) for Lenvatinib
timeFrame: Cycle 1 Day 1: 0.5-10 hours post-dose; Cycle 1 Day 15: 0-12 hours post-dose; Cycle 2 Day 1: 0.5-10 hours post-dose (each cycle length=21 days)
measure: Model Predicted Area Under the Plasma Drug Concentration-time Curve (AUC) for Lenvatinib
timeFrame: Cycle 1 Day 1: 0.5-10 hours post-dose; Cycle 1 Day 15: 0-12 hours post-dose; Cycle 2 Day 1: 0.5-10 hours post-dose (each cycle length=21 days)
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Arizona Oncology Associates, PC- HAL
state: Arizona
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
city: Santa Monica
country: United States
facility: University of California Los Angeles
state: California
city: New Haven
country: United States
facility: Smilow Cancer Hospital at Yale New Haven
state: Connecticut
city: Miami
country: United States
facility: University of Miami Health System
state: Florida
city: Orlando
country: United States
facility: Florida Hospital Cancer Institute
state: Florida
city: Augusta
country: United States
facility: Georgia Cancer Center at Augusta University
state: Georgia
city: Evanston
country: United States
facility: North Shore University Health System
state: Illinois
city: New Orleans
country: United States
facility: University Medical Center New Orleans
state: Louisiana
city: Baltimore
country: United States
facility: Greater Baltimore Medical Center
state: Maryland
city: Wheaton
country: United States
facility: Maryland Oncology Hematology, P.A.
state: Maryland
city: Hackensack
country: United States
facility: John Theurer Cancer Center at Hackensack University Med Ctr
state: New Jersey
city: Teaneck
country: United States
facility: Holy Name Medical Center
state: New Jersey
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Rochester
country: United States
facility: University of Rochester
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Oklahoma City
country: United States
facility: Stephenson Cancer Center
state: Oklahoma
city: Eugene
country: United States
facility: Willamette Valley Cancer Institute and Research Center
state: Oregon
city: Sioux Falls
country: United States
facility: Sanford Gynecology Oncology
state: South Dakota
city: Germantown
country: United States
facility: UT West Cancer Center
state: Tennessee
city: Austin
country: United States
facility: Texas Oncology-South Austin
state: Texas
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center at Dallas
state: Texas
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: San Antonio
country: United States
facility: Texas Oncology-San Antonio Medical Center
state: Texas
city: Salt Lake City
country: United States
facility: Utah Cancer Specialists
state: Utah
city: Berazategui
country: Argentina
facility: Centro de Oncologia e Investigacion Buenos Aires COIBA
state: Buenos Aires
city: Mar del Plata
country: Argentina
facility: Hospital Privado de la Comunidad
state: Buenos Aires
city: Buenos Aires
country: Argentina
facility: Instituto de Investigaciones Metabolicas
city: Buenos Aires
country: Argentina
facility: Hospital Aleman
city: Buenos Aires
country: Argentina
facility: Instituto de Oncologia Angel H. Roffo
city: Buenos Aires
country: Argentina
facility: Instituto Medico Especializado Alexander Fleming
city: La Rioja
country: Argentina
facility: Centro Oncologico Riojano Integral
city: Sydney
country: Australia
facility: Royal North Shore Hospital
state: New South Wales
city: Herston
country: Australia
facility: Royal Brisbane and Women s Hospital
state: Queensland
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre
state: Victoria
city: Subiaco
country: Australia
facility: St John of God
state: Western Australia
city: Goiania
country: Brazil
facility: Hospital Araujo Jorge
state: GO
city: Rio de Janeiro
country: Brazil
facility: Instituto Nacional do Cancer II
state: RJ
city: Porto Alegre
country: Brazil
facility: Hospital de Clinicas de Porto Alegre
state: RS
city: Porto Alegre
country: Brazil
facility: Uniao Brasileira de Educacao e Assistencia Hospital Sao Lucas da Pucrs
state: RS
city: Jau
country: Brazil
facility: Fundacao Dr Amaral Carvalho
state: SP
city: Sao Paulo
country: Brazil
facility: Instituto do Cancer de Sao Paulo - ICESP
state: SP
city: Sao Paulo
country: Brazil
facility: Clinica de Pesquisas e Ctro de Estudos Onc. Ginecol. e Mamaria Ltda
state: SP
city: Belo Horizonte
country: Brazil
facility: Faculdade de Medicina da Universidade Federal de Minas Gerais
city: Calgary
country: Canada
facility: Tom Baker Cancer Centre
state: Alberta
city: Winnipeg
country: Canada
facility: Cancer Care Manitoba
state: Manitoba
city: London
country: Canada
facility: London Health Sciences Centre
state: Ontario
city: Ottawa
country: Canada
facility: Ottawa General Hospital
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Health Science Centre
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
city: Montreal
country: Canada
facility: CIUSSS de l Est de L Ile de Montreal - Hopital Maisonneuve-Rosemont
state: Quebec
city: Montreal
country: Canada
facility: Centre Hospitalier de l Universite de Montreal - CHUM
state: Quebec
city: Montreal
country: Canada
facility: Jewish General Hospital
state: Quebec
city: Sherbrooke
country: Canada
facility: CIUSSS de l'Estrie-CHUS
state: Quebec
city: Quebec
country: Canada
facility: CHU de Quebec-Universite Laval-Hotel Dieu de Quebec
city: Bogota
country: Colombia
facility: Clinica del Country
state: Cundinamarca
city: Cali
country: Colombia
facility: Fundacion Valle del Lili
state: Valle Del Cauca
city: Barranquilla
country: Colombia
facility: Biomelab S A S
city: Bogota
country: Colombia
facility: Clinica Colsanitas S.A. - Sede Clinica Universitaria Colombia
city: Medellin
country: Colombia
facility: Rodrigo Botero SAS
city: Medellin
country: Colombia
facility: Fundacion Colombiana de Cancerologia Clinica Vida
city: Monteria
country: Colombia
facility: Oncomedica S.A.
city: Bordeaux
country: France
facility: Institut Bergonie
city: Caen
country: France
facility: Centre de Lutte Contre le Cancer Francois Baclesse
city: Lille
country: France
facility: Centre Oscar Lambret
city: Lyon
country: France
facility: Centre Leon Berard
city: Montpellier
country: France
facility: Institut Regional du Cancer de Montpellier - ICM
city: Nantes
country: France
facility: Hopital prive du Confluent
city: Paris
country: France
facility: Groupe Hospitalier Broca Cochin Hotel Dieu
city: Paris
country: France
facility: Hopital Diaconesses Croix Saint Simon
city: Pierre Benite
country: France
facility: Centre Hospitalier Lyon Sud
city: Plerin
country: France
facility: Centre Armoricain de Radiotherapie Imagerie medicale et Oncologie
city: Rennes
country: France
facility: Centre Eugene Marquis
city: Villejuif
country: France
facility: Institut Gustave Roussy
city: Berlin
country: Germany
facility: EISAI Trial Site 4
city: Dresden
country: Germany
facility: EISAI Trial Site 2
city: Erlangen
country: Germany
facility: EISAI Trial Site 1
city: Hamburg
country: Germany
facility: EISAI Trial Site 6
city: Rostock
country: Germany
facility: EISAI Trial Site 3
city: Tuebingen
country: Germany
facility: EISAI Trial Site 5
city: Dublin
country: Ireland
facility: Mater Misericordiae University Hospital
city: Beer Sheva
country: Israel
facility: Soroka Medical Center
city: Haifa
country: Israel
facility: Rambam Medical Center
city: Holon
country: Israel
facility: Edith Wolfson Medical Center
city: Jerusalem
country: Israel
facility: Hadassah Medical Center. Ein Kerem
city: Petah Tikva
country: Israel
facility: Rabin Medical Center
city: Ramat Gan
country: Israel
facility: Chaim Sheba Medical Center
city: Catania
country: Italy
facility: Azienda Ospedaliera per l Emergenza Cannizzaro
city: Meldola
country: Italy
facility: Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
city: Milano
country: Italy
facility: Ospedale San Raffaele
city: Milano
country: Italy
facility: Istituto Europeo di Oncologia
city: Milan
country: Italy
facility: Fondazione IRCCS Istituto Nazionale dei Tumori
city: Napoli
country: Italy
facility: Istituto Nazionale Tumori IRCCS Fondazione Pascale
city: Roma
country: Italy
facility: Policlinico Universitario Agostino Gemelli
city: Nagoya
country: Japan
facility: EISAI Trial Site 9
state: Aichi
city: Kashiwa
country: Japan
facility: EISAI Trial Site 18
state: Chiba
city: Matsuyama
country: Japan
facility: EISAI Trial Site 7
state: Ehime
city: Toon
country: Japan
facility: EISAI Trial Site 15
state: Ehime
city: Kurume
country: Japan
facility: EISAI Trial Site 5
state: Fukoka
city: Sapporo
country: Japan
facility: EISAI Trial Site 11
state: Hokkaido
city: Akashi
country: Japan
facility: EISAI Trial Site 8
state: Hyogo
city: Tsukuba
country: Japan
facility: EISAI Trial Site 17
state: Ibaraki
city: Morioka
country: Japan
facility: EISAI Trial Site 4
state: Iwate
city: Isehara
country: Japan
facility: EISAI Trial Site 19
state: Kanagawa
city: Sendai
country: Japan
facility: EISAI Trial Site 14
state: Miyagi
city: Hidaka
country: Japan
facility: EISAI Trial Site 1
state: Saitama
city: Sunto-gun
country: Japan
facility: EISAI Trial Site 2
state: Shizuoka
city: Kagoshima
country: Japan
facility: EISAI Trial Site 16
city: Niigata
country: Japan
facility: EISAI Trial Site 3
city: Tokyo
country: Japan
facility: EISAI Trial Site 10
city: Tokyo
country: Japan
facility: EISAI Trial Site 12
city: Tokyo
country: Japan
facility: EISAI Trial Site 13
city: Tokyo
country: Japan
facility: EISAI Trial Site 6
city: Goyang-si
country: Korea, Republic of
facility: National Cancer Center
state: Gyeonggi-do
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: La Paz
country: Mexico
facility: Investigacion Onco Farmaceutica S de RL de CV
state: Baja California
city: Monterrey
country: Mexico
facility: Alivia Clinica de Alta Especialidad S.A. de C.V.
state: Nuevo Leon
city: Mexico City
country: Mexico
facility: Grupo Medico Camino SC
city: Toluca
country: Mexico
facility: Centro Hemato Oncologico Privado
city: Veracruz
country: Mexico
facility: Faicic S de RL de CV
city: Auckland
country: New Zealand
facility: Auckland City Hospital
city: Krakow
country: Poland
facility: Centrum Onkologii Instytut im. Marii Sklodowskiej Curie
state: Malopolskie
city: Warszawa
country: Poland
facility: Centrum Onkologii. Instytut im. Marii Sklodowskiej-Curie
state: Mazowieckie
city: Bielsko-Biala
country: Poland
facility: Beskidzkie Centrum Onkologii im. Jana Pawla II
city: Gdynia
country: Poland
facility: Szpital Morski im. PCK Szpitale Wojewodzkie w Gdyni Sp. z o.o.
city: Gliwice
country: Poland
facility: Centrum Onkologii Instytut im. Marii Sklodowskiej Curie
city: Lodz
country: Poland
facility: Instytut Centrum Zdrowia Matki Polki
city: Szczecin
country: Poland
facility: Pomorski Uniwersytet Medyczny w Szczecinie
city: Warszawa
country: Poland
facility: Szpital Kliniczny im Ks Anny Mazowieckiej
city: Barnaul
country: Russian Federation
facility: Altay Regional Oncology Dispensary
city: Kazan
country: Russian Federation
facility: Republican Clinical Oncology Dispensary of Tatarstan MoH
city: Moscow
country: Russian Federation
facility: FSBI National Medical Oncology Research Center n.a. N.N. Blokhina
city: Moscow
country: Russian Federation
facility: FSBI-FRCC of Special Types Med. Care & Technologies FMBA of Russia
city: Saint Petersburg
country: Russian Federation
facility: SPb SBHI City Clinical Oncological Dispensary
city: Saint-Petersburg
country: Russian Federation
facility: Leningrad Regional Oncology Center
city: Saransk
country: Russian Federation
facility: Mordovia Republican Oncological Dispensary
city: Tomsk
country: Russian Federation
facility: Tomsk National Research Medical Center of Russian Academy of Sciences
city: Ufa
country: Russian Federation
facility: Republican Clinical Oncology Dispensary of Republic of Bashkortostan
city: Hospitalet de Llobregat
country: Spain
facility: Instituto Catalan de Oncologia ICO - Hospital Duran i Reynals
state: Barcelona
city: Barcelona
country: Spain
facility: Hospital General Universitari Vall d Hebron
city: Madrid
country: Spain
facility: Hospital Universitario Gregorio Maranon
city: Madrid
country: Spain
facility: Clinica Universitaria Navarra - Madrid
city: Madrid
country: Spain
facility: Hospital Ramon y Cajal
city: Madrid
country: Spain
facility: Hospital Clinico San Carlos
city: Valencia
country: Spain
facility: Hospital Universitario y Politecnico La Fe de Valencia
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
state: Beitou
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Veterans General Hospital
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Chang Gung Memorial Hospital of the C.G.M.F.
city: Taichung
country: Taiwan
facility: Taichung Veterans General Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taoyuan
country: Taiwan
facility: Chang Gung Medical Foundation. Linkou Branch
city: Adana
country: Turkey
facility: Basken Adana Dr.Turgut Noyan Uygulama ve Arastirma Merkezi
city: Ankara
country: Turkey
facility: Hacettepe University Medical Faculty
city: Ankara
country: Turkey
facility: Baskent Universitesi Ankara Hastanesi
city: Bursa
country: Turkey
facility: Acibadem Bursa Hastanesi
city: Istanbul
country: Turkey
facility: Acibadem Universitesi Atakent Hastanesi
city: Istanbul
country: Turkey
facility: Florence Nightingale Gayrettepe Hastanesi
city: Izmir
country: Turkey
facility: Ege Universitesi Tip Fakultesi
city: Brighton
country: United Kingdom
facility: Royal Sussex County Hospital
city: Cambridge
country: United Kingdom
facility: Addenbrookes Hospital
city: London
country: United Kingdom
facility: Barts Health NHS Trust - St Bartholomew s Hospital
city: London
country: United Kingdom
facility: Guy s & St Thomas NHS Foundation Trust
city: London
country: United Kingdom
facility: The Royal Marsden Foundation Trust
city: London
country: United Kingdom
facility: The Royal Marsden NHS Foundation Trust
city: London
country: United Kingdom
facility: Imperial College Healthcare NHS Trust
city: London
country: United Kingdom
facility: University College Hospital
city: Southampton
country: United Kingdom
facility: University Hospital Southampton NHS Foundation Trust
Study officials:
affiliation: Eisai Inc.
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Makker V, Colombo N, Casado Herraez A, Santin AD, Colomba E, Miller DS, Fujiwara K, Pignata S, Baron-Hay S, Ray-Coquard I, Shapira-Frommer R, Ushijima K, Sakata J, Yonemori K, Kim YM, Guerra EM, Sanli UA, McCormack MM, Smith AD, Keefe S, Bird S, Dutta L, Orlowski RJ, Lorusso D; Study 309-KEYNOTE-775 Investigators. Lenvatinib plus Pembrolizumab for Advanced Endometrial Cancer. N Engl J Med. 2022 Feb 3;386(5):437-448. doi: 10.1056/NEJMoa2108330. Epub 2022 Jan 19.