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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])

Sponsor
Eisai Inc. (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT03517449
Collaborator
Merck Sharp & Dohme LLC (Industry)
827
Enrollment
169
Locations
2
Arms
55.2
Anticipated Duration (Months)
4.9
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
827 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Jun 11, 2018
Actual Primary Completion Date :
Oct 26, 2020
Anticipated Study Completion Date :
Jan 16, 2023

Arms and Interventions

Arm Intervention/Treatment
Experimental: Lenvatinib 20 mg + Pembrolizumab 200 mg

Participants will receive pembrolizumab 200 milligram (mg) administered by intravenous (IV) infusion on Day 1 of each 21-day cycle plus lenvatinib 20 mg administered orally (PO) once daily (QD) during each 21-day cycle for up to 35 cycles.

Drug: Pembrolizumab
200 mg administered by IV infusion on Day 1 of each 21-day cycle.
Other Names:
  • KEYTRUDA®
  • MK-3475

    • Drug: Lenvatinib
    20 mg administered orally (PO) QD during each 21-day cycle.
    Other Names:
  • LENVIMA®

    		•
    Active Comparator: Treatment of Physician's Choice

    Participants will receive either of the following treatments: doxorubicin 60 milligram per square meter (mg/m^2) administered by IV on Day 1 of each 21-day cycle for up to a maximum cumulative dose of 500 mg/m^2 OR paclitaxel 80 mg/m^2 administered by IV on a 28-day cycle: 3 weeks receiving paclitaxel once a week and 1 week not receiving paclitaxel.

    Drug: Paclitaxel
    80 mg/m^2 administered by IV on a 28-day cycle: 3 weeks receiving paclitaxel once a week and 1 week not receiving paclitaxel.
    Other Names:
  • TAXOL®

    • Drug: Doxorubicin
    60 mg/m^2 administered by IV on Day 1 of each 21-day cycle.
    Other Names:
  • ADRIAMYCIN®

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Progression-free Survival (PFS) [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)]

      PFS was defined as the time from the date of randomization to the date of the first documentation of disease progression, as determined by Blinded Independent Central Review (BICR) per Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 or death due to any cause (whichever occurred first). Disease progression was defined as at least 20 percent (%) increase (including an absolute increase of at least 5 millimeter [mm]) in the sum of diameter of target lesions, taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions. PFS was estimated and analyzed using Kaplan-Meier method.

    2. Overall Survival (OS) [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)]

      OS was defined as the time from the date of randomization to the date of death due to any cause. Participants who were lost to follow-up and those who were alive at the date of data cut-off were censored at the date the participant was last known alive, or date of data cut-off, whichever occurred first.

    Secondary Outcome Measures

    1. Objective Response Rate (ORR) [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)]

      ORR was defined as the percentage of participants who had best overall response of either complete response (CR) or partial response (PR) as determined by BICR per RECIST 1.1. CR was defined as the disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis to less than (<) 10mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.

    2. 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 [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)]

      EORTC QLQ-C30 was a questionnaire which included 30 questions that rates the overall quality of life in cancer participants. The first 28 questions use a 4-point scale (1=not at all to 4=very much) for evaluating function (physical, role, social, cognitive, emotional), symptoms (diarrhea, fatigue, dyspnea, appetite loss, insomnia, nausea/vomiting, constipation, and pain) and financial difficulties. The last 2 questions use a 7-point scale (1=very poor to 7=excellent) to evaluate overall health and quality of life. Scores are transformed to a range of 0 to 100 using a standard EORTC algorithm. A high score for a functional scale represents a high/healthy level of functioning, a high score for the global health status/quality of life (QoL) represents a high QoL, but a high score for a symptom scale/item represents a high level of symptomatology/problem. Data for this outcome measure will be reported after study completion (anticipated study completion date is November 2023).

    3. Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Immune-Related Adverse Events (irAEs) [From the first dose of study drug up to data cutoff date 26 October 2020 (up to approximately 2 years 5 months)]

      TEAEs was defined as AEs that occurred (or worsened, if present at Baseline) after the first dose of study drug through 28 days after the last dose of study drug. AE was defined as any untoward medical occurrence in a participants or clinical study participant temporally associated with the use of study treatment, whether or not considered related to the study treatment. A SAE was defined as any untoward medical occurrence at any dose if it resulted in death or life-threatening AE or required inpatient hospitalization or prolongation of existing hospitalization or resulted in persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions or was a congenital anomaly/birth defect. irAE was defined as any unfavorable and unintended immune-related sign, symptom, or disease (new or worsening) temporally associated with the use of study therapy, regardless of whether or not a causal relationship with the study therapy can be determined.

    4. Percentage of Participants Discontinued Study Treatment Due to TEAEs [From the first dose of study drug up to data cutoff date 26 October 2020 (up to approximately 2 years 5 months)]

      TEAEs was defined as those AEs that occurred (or worsened, if present at Baseline) after the first dose of study drug through 30 days after the last dose of study drug. An AE was defined as any untoward medical occurrence in a participants or clinical study participant temporally associated with the use of study treatment, whether or not considered related to the study treatment.

    5. Time to Treatment Failure Due to Toxicity [From the date of randomization to the date of discontinuation of study treatment due to TEAEs (up to 5 years 5 months)]

      Time to treatment failure due to toxicity was defined as the time from the date of randomization to the date a participant discontinued study treatment due to TEAEs. Data for this outcome measure will be reported after study completion (anticipated study completion date is November 2023).

    6. Model Predicted Apparent Total Clearance (CL/F) for Lenvatinib [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)]

      Sparse pharmacokinetic (PK) samples were collected and analyzed using a population PK approach to estimate PK parameters. Individual predicted CL/F for lenvatinib was then derived from the PK model. The data was collected and analyzed for lenvatinib plus pembrolizumab arm only.

    7. Model Predicted Area Under the Plasma Drug Concentration-time Curve (AUC) for Lenvatinib [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)]

      Sparse PK samples were collected and analyzed using a population PK approach to estimate PK parameters. Individual predicted AUC for lenvatinib was then derived from the PK model. The data was collected and analyzed for lenvatinib plus pembrolizumab arm only.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    Female
    Accepts Healthy Volunteers:
    No
    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.

    1. Has historical or fresh tumor biopsy specimen for determination of mismatch repair (MMR) status.

    2. 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.

    3. Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 7 days of starting study treatment.

    4. 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).

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Arizona Oncology Associates, PC- HAL Phoenix Arizona United States 85016
    2 University of California San Francisco San Francisco California United States 94158
    3 University of California Los Angeles Santa Monica California United States 90095
    4 Smilow Cancer Hospital at Yale New Haven New Haven Connecticut United States 06510
    5 University of Miami Health System Miami Florida United States 33136
    6 Florida Hospital Cancer Institute Orlando Florida United States 32804
    7 Georgia Cancer Center at Augusta University Augusta Georgia United States 30912
    8 North Shore University Health System Evanston Illinois United States 60201
    9 University Medical Center New Orleans New Orleans Louisiana United States 70112
    10 Greater Baltimore Medical Center Baltimore Maryland United States 21204
    11 Maryland Oncology Hematology, P.A. Wheaton Maryland United States 20902
    12 John Theurer Cancer Center at Hackensack University Med Ctr Hackensack New Jersey United States 07601
    13 Holy Name Medical Center Teaneck New Jersey United States 07666
    14 Memorial Sloan Kettering Cancer Center New York New York United States 10022
    15 University of Rochester Rochester New York United States 14642
    16 Duke University Medical Center Durham North Carolina United States 27710
    17 Stephenson Cancer Center Oklahoma City Oklahoma United States 73104
    18 Willamette Valley Cancer Institute and Research Center Eugene Oregon United States 97401
    19 Sanford Gynecology Oncology Sioux Falls South Dakota United States 57104
    20 UT West Cancer Center Germantown Tennessee United States 38138
    21 Texas Oncology-South Austin Austin Texas United States 78745
    22 University of Texas Southwestern Medical Center at Dallas Dallas Texas United States 75390-9032
    23 The University of Texas MD Anderson Cancer Center Houston Texas United States 77030
    24 Texas Oncology-San Antonio Medical Center San Antonio Texas United States 78240
    25 Utah Cancer Specialists Salt Lake City Utah United States 84106
    26 Centro de Oncologia e Investigacion Buenos Aires COIBA Berazategui Buenos Aires Argentina B1884BBF
    27 Hospital Privado de la Comunidad Mar del Plata Buenos Aires Argentina B7602CBM
    28 Instituto de Investigaciones Metabolicas Buenos Aires Argentina C1012AAR
    29 Hospital Aleman Buenos Aires Argentina C1118AAT
    30 Instituto de Oncologia Angel H. Roffo Buenos Aires Argentina C1417DTB
    31 Instituto Medico Especializado Alexander Fleming Buenos Aires Argentina C1426ANZ
    32 Centro Oncologico Riojano Integral La Rioja Argentina F5300COE
    33 Royal North Shore Hospital Sydney New South Wales Australia 2065
    34 Royal Brisbane and Women s Hospital Herston Queensland Australia 4029
    35 Peter MacCallum Cancer Centre Melbourne Victoria Australia 3000
    36 St John of God Subiaco Western Australia Australia 6008
    37 Hospital Araujo Jorge Goiania GO Brazil 74175-120
    38 Instituto Nacional do Cancer II Rio de Janeiro RJ Brazil 20220-410
    39 Hospital de Clinicas de Porto Alegre Porto Alegre RS Brazil 90035-903
    40 Uniao Brasileira de Educacao e Assistencia Hospital Sao Lucas da Pucrs Porto Alegre RS Brazil 90610-000
    41 Fundacao Dr Amaral Carvalho Jau SP Brazil 17210-080
    42 Instituto do Cancer de Sao Paulo - ICESP Sao Paulo SP Brazil 01246-000
    43 Clinica de Pesquisas e Ctro de Estudos Onc. Ginecol. e Mamaria Ltda Sao Paulo SP Brazil 01317-000
    44 Faculdade de Medicina da Universidade Federal de Minas Gerais Belo Horizonte Brazil 30130-100
    45 Tom Baker Cancer Centre Calgary Alberta Canada T2N 4N2
    46 Cancer Care Manitoba Winnipeg Manitoba Canada R3E 0V9
    47 London Health Sciences Centre London Ontario Canada N6A 5W9
    48 Ottawa General Hospital Ottawa Ontario Canada K1H 8L6
    49 Sunnybrook Health Science Centre Toronto Ontario Canada M4N 3M5
    50 Princess Margaret Cancer Centre Toronto Ontario Canada M5G 2M9
    51 CIUSSS de l Est de L Ile de Montreal - Hopital Maisonneuve-Rosemont Montreal Quebec Canada H1T 2M4
    52 Centre Hospitalier de l Universite de Montreal - CHUM Montreal Quebec Canada H2X 3E4
    53 Jewish General Hospital Montreal Quebec Canada H3T 1E2
    54 CIUSSS de l'Estrie-CHUS Sherbrooke Quebec Canada J1H 5N4
    55 CHU de Quebec-Universite Laval-Hotel Dieu de Quebec Quebec Canada G1R 2J6
    56 Clinica del Country Bogota Cundinamarca Colombia 110221
    57 Fundacion Valle del Lili Cali Valle Del Cauca Colombia 760032
    58 Biomelab S A S Barranquilla Colombia 08002
    59 Clinica Colsanitas S.A. - Sede Clinica Universitaria Colombia Bogota Colombia 111321
    60 Rodrigo Botero SAS Medellin Colombia 50015
    61 Fundacion Colombiana de Cancerologia Clinica Vida Medellin Colombia 50032
    62 Oncomedica S.A. Monteria Colombia 230002
    63 Institut Bergonie Bordeaux France 33076
    64 Centre de Lutte Contre le Cancer Francois Baclesse Caen France 14076
    65 Centre Oscar Lambret Lille France 59020
    66 Centre Leon Berard Lyon France 69008
    67 Institut Regional du Cancer de Montpellier - ICM Montpellier France 34298
    68 Hopital prive du Confluent Nantes France 44277
    69 Groupe Hospitalier Broca Cochin Hotel Dieu Paris France 75014
    70 Hopital Diaconesses Croix Saint Simon Paris France 75020
    71 Centre Hospitalier Lyon Sud Pierre Benite France 69310
    72 Centre Armoricain de Radiotherapie Imagerie medicale et Oncologie Plerin France 22190
    73 Centre Eugene Marquis Rennes France 35042
    74 Institut Gustave Roussy Villejuif France 94800
    75 EISAI Trial Site 4 Berlin Germany
    76 EISAI Trial Site 2 Dresden Germany
    77 EISAI Trial Site 1 Erlangen Germany
    78 EISAI Trial Site 6 Hamburg Germany
    79 EISAI Trial Site 3 Rostock Germany
    80 EISAI Trial Site 5 Tuebingen Germany
    81 Mater Misericordiae University Hospital Dublin Ireland D07 R2WY
    82 Soroka Medical Center Beer Sheva Israel 84101
    83 Rambam Medical Center Haifa Israel 3525408
    84 Edith Wolfson Medical Center Holon Israel 5822012
    85 Hadassah Medical Center. Ein Kerem Jerusalem Israel 9112001
    86 Rabin Medical Center Petah Tikva Israel 4941492
    87 Chaim Sheba Medical Center Ramat Gan Israel 5262000
    88 Azienda Ospedaliera per l Emergenza Cannizzaro Catania Italy 95126
    89 Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori Meldola Italy 47014
    90 Ospedale San Raffaele Milano Italy 20132
    91 Istituto Europeo di Oncologia Milano Italy 20141
    92 Fondazione IRCCS Istituto Nazionale dei Tumori Milan Italy 20133
    93 Istituto Nazionale Tumori IRCCS Fondazione Pascale Napoli Italy 80131
    94 Policlinico Universitario Agostino Gemelli Roma Italy 168
    95 EISAI Trial Site 9 Nagoya Aichi Japan
    96 EISAI Trial Site 18 Kashiwa Chiba Japan
    97 EISAI Trial Site 7 Matsuyama Ehime Japan
    98 EISAI Trial Site 15 Toon Ehime Japan
    99 EISAI Trial Site 5 Kurume Fukoka Japan
    100 EISAI Trial Site 11 Sapporo Hokkaido Japan
    101 EISAI Trial Site 8 Akashi Hyogo Japan
    102 EISAI Trial Site 17 Tsukuba Ibaraki Japan
    103 EISAI Trial Site 4 Morioka Iwate Japan
    104 EISAI Trial Site 19 Isehara Kanagawa Japan
    105 EISAI Trial Site 14 Sendai Miyagi Japan
    106 EISAI Trial Site 1 Hidaka Saitama Japan
    107 EISAI Trial Site 2 Sunto-gun Shizuoka Japan
    108 EISAI Trial Site 16 Kagoshima Japan
    109 EISAI Trial Site 3 Niigata Japan
    110 EISAI Trial Site 10 Tokyo Japan
    111 EISAI Trial Site 12 Tokyo Japan
    112 EISAI Trial Site 13 Tokyo Japan
    113 EISAI Trial Site 6 Tokyo Japan
    114 National Cancer Center Goyang-si Gyeonggi-do Korea, Republic of 10408
    115 Seoul National University Hospital Seoul Korea, Republic of 3080
    116 Asan Medical Center Seoul Korea, Republic of 5505
    117 Samsung Medical Center Seoul Korea, Republic of 6351
    118 Investigacion Onco Farmaceutica S de RL de CV La Paz Baja California Mexico 23040
    119 Alivia Clinica de Alta Especialidad S.A. de C.V. Monterrey Nuevo Leon Mexico 64060
    120 Grupo Medico Camino SC Mexico City Mexico 3310
    121 Centro Hemato Oncologico Privado Toluca Mexico 50080
    122 Faicic S de RL de CV Veracruz Mexico 91900
    123 Auckland City Hospital Auckland New Zealand 1023
    124 Centrum Onkologii Instytut im. Marii Sklodowskiej Curie Krakow Malopolskie Poland 31-115
    125 Centrum Onkologii. Instytut im. Marii Sklodowskiej-Curie Warszawa Mazowieckie Poland 02-781
    126 Beskidzkie Centrum Onkologii im. Jana Pawla II Bielsko-Biala Poland 43-300
    127 Szpital Morski im. PCK Szpitale Wojewodzkie w Gdyni Sp. z o.o. Gdynia Poland 81-159
    128 Centrum Onkologii Instytut im. Marii Sklodowskiej Curie Gliwice Poland 44-101
    129 Instytut Centrum Zdrowia Matki Polki Lodz Poland 93-338
    130 Pomorski Uniwersytet Medyczny w Szczecinie Szczecin Poland 70-111
    131 Szpital Kliniczny im Ks Anny Mazowieckiej Warszawa Poland 00-315
    132 Altay Regional Oncology Dispensary Barnaul Russian Federation 656049
    133 Republican Clinical Oncology Dispensary of Tatarstan MoH Kazan Russian Federation 420029
    134 FSBI National Medical Oncology Research Center n.a. N.N. Blokhina Moscow Russian Federation 115478
    135 FSBI-FRCC of Special Types Med. Care & Technologies FMBA of Russia Moscow Russian Federation 115682
    136 SPb SBHI City Clinical Oncological Dispensary Saint Petersburg Russian Federation 198255
    137 Leningrad Regional Oncology Center Saint-Petersburg Russian Federation 191014
    138 Mordovia Republican Oncological Dispensary Saransk Russian Federation 430032
    139 Tomsk National Research Medical Center of Russian Academy of Sciences Tomsk Russian Federation 624028
    140 Republican Clinical Oncology Dispensary of Republic of Bashkortostan Ufa Russian Federation 450054
    141 Instituto Catalan de Oncologia ICO - Hospital Duran i Reynals Hospitalet de Llobregat Barcelona Spain 8908
    142 Hospital General Universitari Vall d Hebron Barcelona Spain 8035
    143 Hospital Universitario Gregorio Maranon Madrid Spain 28007
    144 Clinica Universitaria Navarra - Madrid Madrid Spain 28027
    145 Hospital Ramon y Cajal Madrid Spain 28034
    146 Hospital Clinico San Carlos Madrid Spain 28040
    147 Hospital Universitario y Politecnico La Fe de Valencia Valencia Spain 46026
    148 Taipei Veterans General Hospital Taipei Beitou Taiwan 11217
    149 Kaohsiung Veterans General Hospital Kaohsiung Taiwan 813
    150 Kaohsiung Chang Gung Memorial Hospital of the C.G.M.F. Kaohsiung Taiwan 833
    151 Taichung Veterans General Hospital Taichung Taiwan 40705
    152 National Taiwan University Hospital Taipei Taiwan 10002
    153 Chang Gung Medical Foundation. Linkou Branch Taoyuan Taiwan 33305
    154 Basken Adana Dr.Turgut Noyan Uygulama ve Arastirma Merkezi Adana Turkey 01250
    155 Hacettepe University Medical Faculty Ankara Turkey 06000
    156 Baskent Universitesi Ankara Hastanesi Ankara Turkey 06490
    157 Acibadem Bursa Hastanesi Bursa Turkey 16110
    158 Acibadem Universitesi Atakent Hastanesi Istanbul Turkey 34303
    159 Florence Nightingale Gayrettepe Hastanesi Istanbul Turkey 34349
    160 Ege Universitesi Tip Fakultesi Izmir Turkey 35040
    161 Royal Sussex County Hospital Brighton United Kingdom BN2 5BE
    162 Addenbrookes Hospital Cambridge United Kingdom CB2 0QQ
    163 Barts Health NHS Trust - St Bartholomew s Hospital London United Kingdom EC1A 7BE
    164 Guy s & St Thomas NHS Foundation Trust London United Kingdom SE1 9RT
    165 The Royal Marsden Foundation Trust London United Kingdom SM2 5PT
    166 The Royal Marsden NHS Foundation Trust London United Kingdom SW3 6JJ
    167 Imperial College Healthcare NHS Trust London United Kingdom W12 0HS
    168 University College Hospital London United Kingdom WC1E 6AG
    169 University Hospital Southampton NHS Foundation Trust Southampton United Kingdom SO16 6YD

    Sponsors and Collaborators

    • Eisai Inc.
    • Merck Sharp & Dohme LLC

    Investigators

    • Study Director: Medical Director, Eisai Inc.

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Eisai Inc.
    ClinicalTrials.gov Identifier:
    NCT03517449
    Other Study ID Numbers:
    • E7080-G000-309
    • 2017-004387-35
    • MK3475-775
    First Posted:
    May 7, 2018
    Last Update Posted:
    Mar 29, 2022
    Last Verified:
    Dec 1, 2021
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Eisai Inc.
    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
    Additional relevant MeSH terms:
    Endometrial Neoplasms
    Paclitaxel
    Doxorubicin
    Pembrolizumab
    Lenvatinib

    Study Results

    Participant Flow

    Recruitment Details Participants took part in the study at 167 investigative sites in Argentina, Australia, Brazil, Canada, Colombia, France, Germany, Ireland, Israel, Italy, Japan, Korea, Mexico, New Zealand, Poland, Russia, Spain, Taiwan, Turkey, United Kingdom and the United States. Results in this summary are reported based on the primary completion date (26 October 2020) of the study.
    Pre-assignment Detail A total of 1178 participants were screened, of which 351 were screen failures and 827 were enrolled and randomized, out of which 794 participants were treated.
    Arm/Group Title Lenvatinib 20 mg + Pembrolizumab 200 mg Treatment of Physician's Choice (TPC): Doxorubicin or Paclitaxel
    Arm/Group Description Participants with Endometrial cancer (EC) received lenvatinib 20 milligrams (mg) orally, once daily, plus pembrolizumab 200 mg intravenously, every 3 weeks in each 21-day cycle. Participants continued to receive treatment until disease progression, development of unacceptable toxicity, withdrawal of consent, completion of 35 treatments (approximately 2 years) with pembrolizumab, or sponsor termination of the study. Participants with EC received either doxorubicin 60 milligrams per square meter (mg/m^2) intravenously, every 3 weeks, in each 21-day treatment cycle, or paclitaxel 80 mg/m^2 intravenously, weekly (3 weeks on/1 week off), in each 28-day treatment cycle. Participants continued to receive treatment until a lifetime cumulative dose of 500 mg/m^2 doxorubicin, a maximum dose of paclitaxel per standard of care, or until disease progression, development of unacceptable toxicity, withdrawal of consent, or sponsor termination of the study.
    Period Title: Overall Study
    STARTED 411 416
    Treated 406 388
    COMPLETED 0 0
    NOT COMPLETED 411 416

    Baseline Characteristics

    Arm/Group Title Lenvatinib 20 mg + Pembrolizumab 200 mg Treatment of Physician's Choice (TPC): Doxorubicin or Paclitaxel Total
    Arm/Group Description Participants with EC received lenvatinib 20 mg orally, once daily, plus pembrolizumab 200 mg intravenously, every 3 weeks in each 21-day cycle. Participants continued to receive treatment until disease progression, development of unacceptable toxicity, withdrawal of consent, completion of 35 treatments (approximately 2 years) with pembrolizumab, or sponsor termination of the study. Participants with EC received either doxorubicin 60 mg/m^2 intravenously, every 3 weeks, in each 21-day treatment cycle, or paclitaxel 80 mg/m^2 intravenously, weekly (3 weeks on/1 week off), in each 28-day treatment cycle. Participants continued to receive treatment until a lifetime cumulative dose of 500 mg/m^2 doxorubicin, a maximum dose of paclitaxel per standard of care, or until disease progression, development of unacceptable toxicity, withdrawal of consent, or sponsor termination of the study. Total of all reporting groups
    Overall Participants 411 416 827
    Age (Years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Years]
    63.2
    (9.1)
    63.8
    (9.2)
    63.5
    (9.1)
    Sex: Female, Male (Count of Participants)
    Female
    411
    100%
    416
    100%
    827
    100%
    Male
    0
    0%
    0
    0%
    0
    0%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    60
    14.6%
    73
    17.5%
    133
    16.1%
    Not Hispanic or Latino
    308
    74.9%
    287
    69%
    595
    71.9%
    Unknown or Not Reported
    43
    10.5%
    56
    13.5%
    99
    12%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    4
    1%
    7
    1.7%
    11
    1.3%
    Asian
    85
    20.7%
    92
    22.1%
    177
    21.4%
    Native Hawaiian or Other Pacific Islander
    1
    0.2%
    0
    0%
    1
    0.1%
    Black or African American
    17
    4.1%
    14
    3.4%
    31
    3.7%
    White
    261
    63.5%
    246
    59.1%
    507
    61.3%
    More than one race
    7
    1.7%
    13
    3.1%
    20
    2.4%
    Unknown or Not Reported
    36
    8.8%
    44
    10.6%
    80
    9.7%

    Outcome Measures

    1. Primary Outcome
    Title Progression-free Survival (PFS)
    Description PFS was defined as the time from the date of randomization to the date of the first documentation of disease progression, as determined by Blinded Independent Central Review (BICR) per Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 or death due to any cause (whichever occurred first). Disease progression was defined as at least 20 percent (%) increase (including an absolute increase of at least 5 millimeter [mm]) in the sum of diameter of target lesions, taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions. PFS was estimated and analyzed using Kaplan-Meier method.
    Time Frame 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)

    Outcome Measure Data

    Analysis Population Description
    The ITT population included all randomized participants.
    Arm/Group Title Lenvatinib 20 mg + Pembrolizumab 200 mg Treatment of Physician's Choice (TPC): Doxorubicin or Paclitaxel
    Arm/Group Description Participants with EC received lenvatinib 20 mg orally, once daily, plus pembrolizumab 200 mg intravenously, every 3 weeks in each 21-day cycle. Participants continued to receive treatment until disease progression, development of unacceptable toxicity, withdrawal of consent, completion of 35 treatments (approximately 2 years) with pembrolizumab, or sponsor termination of the study. Participants with EC received either doxorubicin 60 mg/m^2 intravenously, every 3 weeks, in each 21-day treatment cycle, or paclitaxel 80 mg/m^2 intravenously, weekly (3 weeks on/1 week off), in each 28-day treatment cycle. Participants continued to receive treatment until a lifetime cumulative dose of 500 mg/m^2 doxorubicin, a maximum dose of paclitaxel per standard of care, or until disease progression, development of unacceptable toxicity, withdrawal of consent, or sponsor termination of the study.
    Measure Participants 411 416
    Median (95% Confidence Interval) [Months]
    7.2
    3.8
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Lenvatinib 20 mg + Pembrolizumab 200 mg, Treatment of Physician's Choice (TPC): Doxorubicin or Paclitaxel
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method Log Rank
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.56
    Confidence Interval (2-Sided) 95%
    0.47 to 0.66
    Parameter Dispersion Type:
    Value:
    Estimation Comments Regression, Cox method
    2. Primary Outcome
    Title Overall Survival (OS)
    Description OS was defined as the time from the date of randomization to the date of death due to any cause. Participants who were lost to follow-up and those who were alive at the date of data cut-off were censored at the date the participant was last known alive, or date of data cut-off, whichever occurred first.
    Time Frame 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)

    Outcome Measure Data

    Analysis Population Description
    The ITT population included all randomized participants.
    Arm/Group Title Lenvatinib 20 mg + Pembrolizumab 200 mg Treatment of Physician's Choice (TPC): Doxorubicin or Paclitaxel
    Arm/Group Description Participants with EC received lenvatinib 20 mg orally, once daily, plus pembrolizumab 200 mg intravenously, every 3 weeks in each 21-day cycle. Participants continued to receive treatment until disease progression, development of unacceptable toxicity, withdrawal of consent, completion of 35 treatments (approximately 2 years) with pembrolizumab, or sponsor termination of the study. Participants with EC received either doxorubicin 60 mg/m^2 intravenously, every 3 weeks, in each 21-day treatment cycle, or paclitaxel 80 mg/m^2 intravenously, weekly (3 weeks on/1 week off), in each 28-day treatment cycle. Participants continued to receive treatment until a lifetime cumulative dose of 500 mg/m^2 doxorubicin, a maximum dose of paclitaxel per standard of care, or until disease progression, development of unacceptable toxicity, withdrawal of consent, or sponsor termination of the study.
    Measure Participants 411 416
    Median (95% Confidence Interval) [Months]
    18.3
    11.4
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Lenvatinib 20 mg + Pembrolizumab 200 mg, Treatment of Physician's Choice (TPC): Doxorubicin or Paclitaxel
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method Log Rank
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.62
    Confidence Interval (2-Sided) 95%
    0.51 to 0.75
    Parameter Dispersion Type:
    Value:
    Estimation Comments Regression, Cox method
    3. Secondary Outcome
    Title Objective Response Rate (ORR)
    Description ORR was defined as the percentage of participants who had best overall response of either complete response (CR) or partial response (PR) as determined by BICR per RECIST 1.1. CR was defined as the disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis to less than (<) 10mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.
    Time Frame 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)

    Outcome Measure Data

    Analysis Population Description
    The ITT population included all randomized participants.
    Arm/Group Title Lenvatinib 20 mg + Pembrolizumab 200 mg Treatment of Physician's Choice (TPC): Doxorubicin or Paclitaxel
    Arm/Group Description Participants with EC received lenvatinib 20 mg orally, once daily, plus pembrolizumab 200 mg intravenously, every 3 weeks in each 21-day cycle. Participants continued to receive treatment until disease progression, development of unacceptable toxicity, withdrawal of consent, completion of 35 treatments (approximately 2 years) with pembrolizumab, or sponsor termination of the study. Participants with EC received either doxorubicin 60 mg/m^2 intravenously, every 3 weeks, in each 21-day treatment cycle, or paclitaxel 80 mg/m^2 intravenously, weekly (3 weeks on/1 week off), in each 28-day treatment cycle. Participants continued to receive treatment until a lifetime cumulative dose of 500 mg/m^2 doxorubicin, a maximum dose of paclitaxel per standard of care, or until disease progression, development of unacceptable toxicity, withdrawal of consent, or sponsor termination of the study.
    Measure Participants 411 416
    Number (95% Confidence Interval) [Percentage of participants]
    31.9
    7.8%
    14.7
    3.5%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Lenvatinib 20 mg + Pembrolizumab 200 mg, Treatment of Physician's Choice (TPC): Doxorubicin or Paclitaxel
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method Miettinen & Nurminen method
    Comments
    Method of Estimation Estimation Parameter Difference in Percent
    Estimated Value 17.2
    Confidence Interval (2-Sided) 95%
    11.5 to 22.9
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    4. Secondary Outcome
    Title 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
    Description EORTC QLQ-C30 was a questionnaire which included 30 questions that rates the overall quality of life in cancer participants. The first 28 questions use a 4-point scale (1=not at all to 4=very much) for evaluating function (physical, role, social, cognitive, emotional), symptoms (diarrhea, fatigue, dyspnea, appetite loss, insomnia, nausea/vomiting, constipation, and pain) and financial difficulties. The last 2 questions use a 7-point scale (1=very poor to 7=excellent) to evaluate overall health and quality of life. Scores are transformed to a range of 0 to 100 using a standard EORTC algorithm. A high score for a functional scale represents a high/healthy level of functioning, a high score for the global health status/quality of life (QoL) represents a high QoL, but a high score for a symptom scale/item represents a high level of symptomatology/problem. Data for this outcome measure will be reported after study completion (anticipated study completion date is November 2023).
    Time Frame 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)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    5. Secondary Outcome
    Title Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Immune-Related Adverse Events (irAEs)
    Description TEAEs was defined as AEs that occurred (or worsened, if present at Baseline) after the first dose of study drug through 28 days after the last dose of study drug. AE was defined as any untoward medical occurrence in a participants or clinical study participant temporally associated with the use of study treatment, whether or not considered related to the study treatment. A SAE was defined as any untoward medical occurrence at any dose if it resulted in death or life-threatening AE or required inpatient hospitalization or prolongation of existing hospitalization or resulted in persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions or was a congenital anomaly/birth defect. irAE was defined as any unfavorable and unintended immune-related sign, symptom, or disease (new or worsening) temporally associated with the use of study therapy, regardless of whether or not a causal relationship with the study therapy can be determined.
    Time Frame From the first dose of study drug up to data cutoff date 26 October 2020 (up to approximately 2 years 5 months)

    Outcome Measure Data

    Analysis Population Description
    Safety analysis population included all randomized participants who received at least 1 dose of study treatment.
    Arm/Group Title Lenvatinib 20 mg + Pembrolizumab 200 mg Treatment of Physician's Choice (TPC): Doxorubicin or Paclitaxel
    Arm/Group Description Participants with EC received lenvatinib 20 mg orally, once daily, plus pembrolizumab 200 mg intravenously, every 3 weeks in each 21-day cycle. Participants continued to receive treatment until disease progression, development of unacceptable toxicity, withdrawal of consent, completion of 35 treatments (approximately 2 years) with pembrolizumab, or sponsor termination of the study. Participants with EC received either doxorubicin 60 mg/m^2 intravenously, every 3 weeks, in each 21-day treatment cycle, or paclitaxel 80 mg/m^2 intravenously, weekly (3 weeks on/1 week off), in each 28-day treatment cycle. Participants continued to receive treatment until a lifetime cumulative dose of 500 mg/m^2 doxorubicin, a maximum dose of paclitaxel per standard of care, or until disease progression, development of unacceptable toxicity, withdrawal of consent, or sponsor termination of the study.
    Measure Participants 406 388
    Participants With TEAEs
    405
    98.5%
    386
    92.8%
    Participants With SAEs
    214
    52.1%
    118
    28.4%
    Participants With irAEs
    273
    66.4%
    17
    4.1%
    6. Secondary Outcome
    Title Percentage of Participants Discontinued Study Treatment Due to TEAEs
    Description TEAEs was defined as those AEs that occurred (or worsened, if present at Baseline) after the first dose of study drug through 30 days after the last dose of study drug. An AE was defined as any untoward medical occurrence in a participants or clinical study participant temporally associated with the use of study treatment, whether or not considered related to the study treatment.
    Time Frame From the first dose of study drug up to data cutoff date 26 October 2020 (up to approximately 2 years 5 months)

    Outcome Measure Data

    Analysis Population Description
    Safety analysis population included all randomized participants who received at least 1 dose of study treatment.
    Arm/Group Title Lenvatinib 20 mg + Pembrolizumab 200 mg Treatment of Physician's Choice (TPC): Doxorubicin or Paclitaxel
    Arm/Group Description Participants with EC received lenvatinib 20 mg orally, once daily, plus pembrolizumab 200 mg intravenously, every 3 weeks in each 21-day cycle. Participants continued to receive treatment until disease progression, development of unacceptable toxicity, withdrawal of consent, completion of 35 treatments (approximately 2 years) with pembrolizumab, or sponsor termination of the study. Participants with EC received either doxorubicin 60 mg/m^2 intravenously, every 3 weeks, in each 21-day treatment cycle, or paclitaxel 80 mg/m^2 intravenously, weekly (3 weeks on/1 week off), in each 28-day treatment cycle. Participants continued to receive treatment until a lifetime cumulative dose of 500 mg/m^2 doxorubicin, a maximum dose of paclitaxel per standard of care, or until disease progression, development of unacceptable toxicity, withdrawal of consent, or sponsor termination of the study.
    Measure Participants 406 388
    Number [Percentage of participants]
    33.0
    8%
    8.0
    1.9%
    7. Secondary Outcome
    Title Time to Treatment Failure Due to Toxicity
    Description Time to treatment failure due to toxicity was defined as the time from the date of randomization to the date a participant discontinued study treatment due to TEAEs. Data for this outcome measure will be reported after study completion (anticipated study completion date is November 2023).
    Time Frame From the date of randomization to the date of discontinuation of study treatment due to TEAEs (up to 5 years 5 months)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    8. Secondary Outcome
    Title Model Predicted Apparent Total Clearance (CL/F) for Lenvatinib
    Description Sparse pharmacokinetic (PK) samples were collected and analyzed using a population PK approach to estimate PK parameters. Individual predicted CL/F for lenvatinib was then derived from the PK model. The data was collected and analyzed for lenvatinib plus pembrolizumab arm only.
    Time Frame 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)

    Outcome Measure Data

    Analysis Population Description
    The population pharmacokinetic analysis set includes all the participants who have received at least 1 dose of study treatment with documented dosing history in the lenvatinib plus pembrolizumab arm, and have measurable plasma levels of lenvatinib. Here "overall number of participants analyzed" signifies participants who were evaluable for this outcome measure.
    Arm/Group Title Lenvatinib 20 mg + Pembrolizumab 200 mg
    Arm/Group Description Participants with EC received lenvatinib 20 mg orally, once daily, plus pembrolizumab 200 mg intravenously, every 3 weeks in each 21-day cycle. Participants continued to receive treatment until disease progression, development of unacceptable toxicity, withdrawal of consent, completion of 35 treatments (approximately 2 years) with pembrolizumab, or sponsor termination of the study.
    Measure Participants 403
    Mean (Standard Deviation) [liter per hour (L/h)]
    4.69
    (1.39)
    9. Secondary Outcome
    Title Model Predicted Area Under the Plasma Drug Concentration-time Curve (AUC) for Lenvatinib
    Description Sparse PK samples were collected and analyzed using a population PK approach to estimate PK parameters. Individual predicted AUC for lenvatinib was then derived from the PK model. The data was collected and analyzed for lenvatinib plus pembrolizumab arm only.
    Time Frame 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)

    Outcome Measure Data

    Analysis Population Description
    The population pharmacokinetic analysis set includes all the participants who have received at least 1 dose of study treatment with documented dosing history in the lenvatinib plus pembrolizumab arm, and have measurable plasma levels of lenvatinib. Here "overall number of participants analyzed" signifies participants who were evaluable for this outcome measure.
    Arm/Group Title Lenvatinib 20 mg + Pembrolizumab 200 mg
    Arm/Group Description Participants with EC received lenvatinib 20 mg orally, once daily, plus pembrolizumab 200 mg intravenously, every 3 weeks in each 21-day cycle. Participants continued to receive treatment until disease progression, development of unacceptable toxicity, withdrawal of consent, completion of 35 treatments (approximately 2 years) with pembrolizumab, or sponsor termination of the study.
    Measure Participants 403
    Mean (Standard Deviation) [nanogram*hour per milliliter (ng*h/mL)]
    4134
    (1350)

    Adverse Events

    Time Frame From the first dose of study drug up to data cutoff date 26 October 2020 (up to approximately 2 years 5 months)
    Adverse Event Reporting Description
    Arm/Group Title Lenvatinib 20 mg + Pembrolizumab 200 mg Treatment of Physician's Choice: (TPC) Doxorubicin or Paclitaxel
    Arm/Group Description Participants with EC received lenvatinib 20 mg orally, once daily, plus pembrolizumab 200 mg intravenously, every 3 weeks in each 21-day cycle. Participants continued to receive treatment until disease progression, development of unacceptable toxicity, withdrawal of consent, completion of 35 treatments (approximately 2 years) with pembrolizumab, or sponsor termination of the study. Participants with EC received either doxorubicin 60 mg/m^2 intravenously, every 3 weeks, in each 21-day treatment cycle, or paclitaxel 80 mg/m^2 intravenously, weekly (3 weeks on/1 week off), in each 28-day treatment cycle. Participants continued to receive treatment until a lifetime cumulative dose of 500 mg/m^2 doxorubicin, a maximum dose of paclitaxel per standard of care, or until disease progression, development of unacceptable toxicity, withdrawal of consent, or sponsor termination of the study.
    All Cause Mortality
    Lenvatinib 20 mg + Pembrolizumab 200 mg Treatment of Physician's Choice: (TPC) Doxorubicin or Paclitaxel
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 184/406 (45.3%) 236/388 (60.8%)
    Serious Adverse Events
    Lenvatinib 20 mg + Pembrolizumab 200 mg Treatment of Physician's Choice: (TPC) Doxorubicin or Paclitaxel
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 214/406 (52.7%) 118/388 (30.4%)
    Blood and lymphatic system disorders
    Anaemia 1/406 (0.2%) 9/388 (2.3%)
    Febrile bone marrow aplasia 0/406 (0%) 1/388 (0.3%)
    Febrile neutropenia 2/406 (0.5%) 16/388 (4.1%)
    Leukocytosis 0/406 (0%) 1/388 (0.3%)
    Leukopenia 0/406 (0%) 2/388 (0.5%)
    Neutropenia 1/406 (0.2%) 7/388 (1.8%)
    Neutrophilia 0/406 (0%) 1/388 (0.3%)
    Pancytopenia 1/406 (0.2%) 0/388 (0%)
    Thrombocytopenia 1/406 (0.2%) 1/388 (0.3%)
    Thrombotic microangiopathy 1/406 (0.2%) 0/388 (0%)
    Cardiac disorders
    Acute coronary syndrome 2/406 (0.5%) 0/388 (0%)
    Acute myocardial infarction 3/406 (0.7%) 0/388 (0%)
    Atrial fibrillation 1/406 (0.2%) 2/388 (0.5%)
    Bundle branch block left 1/406 (0.2%) 0/388 (0%)
    Cardiac failure 0/406 (0%) 3/388 (0.8%)
    Cardiac failure congestive 0/406 (0%) 2/388 (0.5%)
    Cardiogenic shock 0/406 (0%) 2/388 (0.5%)
    Left ventricular dysfunction 0/406 (0%) 1/388 (0.3%)
    Myocardial infarction 1/406 (0.2%) 0/388 (0%)
    Myocarditis 1/406 (0.2%) 0/388 (0%)
    Pericardial effusion 1/406 (0.2%) 0/388 (0%)
    Right ventricular dysfunction 1/406 (0.2%) 0/388 (0%)
    Sinus tachycardia 1/406 (0.2%) 0/388 (0%)
    Stress cardiomyopathy 1/406 (0.2%) 0/388 (0%)
    Supraventricular tachycardia 0/406 (0%) 2/388 (0.5%)
    Toxic cardiomyopathy 0/406 (0%) 1/388 (0.3%)
    Ventricular fibrillation 1/406 (0.2%) 0/388 (0%)
    Endocrine disorders
    Adrenal insufficiency 3/406 (0.7%) 0/388 (0%)
    Adrenocorticotropic hormone deficiency 1/406 (0.2%) 0/388 (0%)
    Hyperthyroidism 3/406 (0.7%) 0/388 (0%)
    Hypophysitis 1/406 (0.2%) 0/388 (0%)
    Hypothyroidism 2/406 (0.5%) 0/388 (0%)
    Eye disorders
    Iridocyclitis 1/406 (0.2%) 0/388 (0%)
    Gastrointestinal disorders
    Abdominal pain 4/406 (1%) 1/388 (0.3%)
    Abdominal pain lower 1/406 (0.2%) 0/388 (0%)
    Anal fissure 1/406 (0.2%) 0/388 (0%)
    Ascites 2/406 (0.5%) 2/388 (0.5%)
    Colitis 7/406 (1.7%) 1/388 (0.3%)
    Colonic fistula 0/406 (0%) 2/388 (0.5%)
    Constipation 3/406 (0.7%) 0/388 (0%)
    Diarrhoea 10/406 (2.5%) 3/388 (0.8%)
    Diverticular perforation 1/406 (0.2%) 0/388 (0%)
    Duodenal obstruction 0/406 (0%) 1/388 (0.3%)
    Enterocolitis 1/406 (0.2%) 0/388 (0%)
    Gastritis erosive 1/406 (0.2%) 0/388 (0%)
    Gastrointestinal haemorrhage 2/406 (0.5%) 0/388 (0%)
    Gastrointestinal perforation 2/406 (0.5%) 0/388 (0%)
    Gastrointestinal toxicity 0/406 (0%) 1/388 (0.3%)
    Gastrooesophageal reflux disease 1/406 (0.2%) 0/388 (0%)
    Ileus 4/406 (1%) 0/388 (0%)
    Immune-mediated pancreatitis 1/406 (0.2%) 0/388 (0%)
    Intestinal fistula 1/406 (0.2%) 0/388 (0%)
    Intestinal obstruction 5/406 (1.2%) 3/388 (0.8%)
    Intestinal perforation 3/406 (0.7%) 0/388 (0%)
    Large intestinal obstruction 1/406 (0.2%) 0/388 (0%)
    Large intestine perforation 2/406 (0.5%) 0/388 (0%)
    Lower gastrointestinal haemorrhage 1/406 (0.2%) 0/388 (0%)
    Lower gastrointestinal perforation 1/406 (0.2%) 0/388 (0%)
    Malignant gastrointestinal obstruction 1/406 (0.2%) 0/388 (0%)
    Mechanical ileus 1/406 (0.2%) 0/388 (0%)
    Nausea 3/406 (0.7%) 1/388 (0.3%)
    Pancreatitis acute 2/406 (0.5%) 0/388 (0%)
    Proctalgia 1/406 (0.2%) 0/388 (0%)
    Rectal perforation 1/406 (0.2%) 0/388 (0%)
    Small intestinal obstruction 3/406 (0.7%) 2/388 (0.5%)
    Stomatitis 0/406 (0%) 1/388 (0.3%)
    Subileus 2/406 (0.5%) 1/388 (0.3%)
    Umbilical hernia 1/406 (0.2%) 0/388 (0%)
    Vomiting 9/406 (2.2%) 3/388 (0.8%)
    General disorders
    Asthenia 3/406 (0.7%) 2/388 (0.5%)
    Catheter site inflammation 0/406 (0%) 1/388 (0.3%)
    Condition aggravated 0/406 (0%) 1/388 (0.3%)
    Death 5/406 (1.2%) 3/388 (0.8%)
    Device related thrombosis 1/406 (0.2%) 0/388 (0%)
    Fatigue 2/406 (0.5%) 0/388 (0%)
    General physical health deterioration 3/406 (0.7%) 1/388 (0.3%)
    Generalised oedema 2/406 (0.5%) 0/388 (0%)
    Hyperpyrexia 0/406 (0%) 1/388 (0.3%)
    Mucosal inflammation 1/406 (0.2%) 0/388 (0%)
    Multiple organ dysfunction syndrome 1/406 (0.2%) 2/388 (0.5%)
    Oedema peripheral 1/406 (0.2%) 1/388 (0.3%)
    Perforated ulcer 1/406 (0.2%) 0/388 (0%)
    Pyrexia 8/406 (2%) 3/388 (0.8%)
    Hepatobiliary disorders
    Bile duct stone 1/406 (0.2%) 0/388 (0%)
    Biliary obstruction 1/406 (0.2%) 0/388 (0%)
    Cholangitis 3/406 (0.7%) 0/388 (0%)
    Cholecystitis 7/406 (1.7%) 0/388 (0%)
    Cholecystitis acute 1/406 (0.2%) 0/388 (0%)
    Hepatic failure 1/406 (0.2%) 0/388 (0%)
    Hepatic function abnormal 2/406 (0.5%) 0/388 (0%)
    Hepatitis 1/406 (0.2%) 0/388 (0%)
    Hepatobiliary disease 0/406 (0%) 1/388 (0.3%)
    Hepatotoxicity 1/406 (0.2%) 0/388 (0%)
    Immune-mediated hepatitis 2/406 (0.5%) 0/388 (0%)
    Liver disorder 2/406 (0.5%) 0/388 (0%)
    Immune system disorders
    Anaphylactic reaction 1/406 (0.2%) 0/388 (0%)
    Anaphylactic shock 1/406 (0.2%) 0/388 (0%)
    Hypersensitivity 3/406 (0.7%) 0/388 (0%)
    Infections and infestations
    Abdominal sepsis 0/406 (0%) 1/388 (0.3%)
    Appendicitis 2/406 (0.5%) 0/388 (0%)
    Appendicitis perforated 1/406 (0.2%) 0/388 (0%)
    Arthritis bacterial 1/406 (0.2%) 0/388 (0%)
    Bacteraemia 1/406 (0.2%) 2/388 (0.5%)
    Bacterial infection 1/406 (0.2%) 0/388 (0%)
    Cellulitis 0/406 (0%) 2/388 (0.5%)
    Cystitis 1/406 (0.2%) 0/388 (0%)
    Device related infection 2/406 (0.5%) 2/388 (0.5%)
    Diarrhoea infectious 1/406 (0.2%) 0/388 (0%)
    Encephalitis 1/406 (0.2%) 0/388 (0%)
    Escherichia bacteraemia 1/406 (0.2%) 0/388 (0%)
    Gastroenteritis 3/406 (0.7%) 1/388 (0.3%)
    Gastroenteritis Escherichia coli 1/406 (0.2%) 0/388 (0%)
    Gastroenteritis norovirus 1/406 (0.2%) 0/388 (0%)
    Infected fistula 1/406 (0.2%) 0/388 (0%)
    Infection 2/406 (0.5%) 1/388 (0.3%)
    Influenza 2/406 (0.5%) 2/388 (0.5%)
    Lower respiratory tract infection 1/406 (0.2%) 0/388 (0%)
    Meningitis bacterial 1/406 (0.2%) 0/388 (0%)
    Oesophageal candidiasis 0/406 (0%) 1/388 (0.3%)
    Pelvic abscess 0/406 (0%) 1/388 (0.3%)
    Peritonitis 2/406 (0.5%) 0/388 (0%)
    Pneumonia 6/406 (1.5%) 3/388 (0.8%)
    Postoperative wound infection 3/406 (0.7%) 0/388 (0%)
    Psoas abscess 1/406 (0.2%) 0/388 (0%)
    Pyelonephritis 1/406 (0.2%) 1/388 (0.3%)
    Pyelonephritis acute 0/406 (0%) 1/388 (0.3%)
    Retroperitoneal abscess 0/406 (0%) 1/388 (0.3%)
    Sepsis 5/406 (1.2%) 5/388 (1.3%)
    Septic shock 0/406 (0%) 1/388 (0.3%)
    Sialoadenitis 1/406 (0.2%) 0/388 (0%)
    Sinusitis 1/406 (0.2%) 0/388 (0%)
    Skin infection 1/406 (0.2%) 0/388 (0%)
    Staphylococcal bacteraemia 1/406 (0.2%) 0/388 (0%)
    Tonsillitis 1/406 (0.2%) 0/388 (0%)
    Upper respiratory tract infection 1/406 (0.2%) 0/388 (0%)
    Urinary tract infection 13/406 (3.2%) 2/388 (0.5%)
    Urosepsis 1/406 (0.2%) 2/388 (0.5%)
    Vaginal abscess 1/406 (0.2%) 0/388 (0%)
    Vaginal infection 1/406 (0.2%) 0/388 (0%)
    Wound infection 1/406 (0.2%) 0/388 (0%)
    Injury, poisoning and procedural complications
    Craniocerebral injury 1/406 (0.2%) 0/388 (0%)
    Gastroenteritis radiation 1/406 (0.2%) 0/388 (0%)
    Postoperative ileus 1/406 (0.2%) 0/388 (0%)
    Radius fracture 0/406 (0%) 1/388 (0.3%)
    Skull fractured base 1/406 (0.2%) 0/388 (0%)
    Subdural haematoma 0/406 (0%) 1/388 (0.3%)
    Vascular procedure complication 0/406 (0%) 1/388 (0.3%)
    Wound dehiscence 1/406 (0.2%) 0/388 (0%)
    Investigations
    Alanine aminotransferase increased 0/406 (0%) 1/388 (0.3%)
    Aspartate aminotransferase increased 0/406 (0%) 1/388 (0.3%)
    Blood alkaline phosphatase increased 0/406 (0%) 1/388 (0.3%)
    Blood creatine phosphokinase increased 1/406 (0.2%) 0/388 (0%)
    Blood creatinine increased 1/406 (0.2%) 0/388 (0%)
    ECG signs of myocardial ischaemia 1/406 (0.2%) 0/388 (0%)
    Ejection fraction decreased 0/406 (0%) 1/388 (0.3%)
    Electrocardiogram QT prolonged 1/406 (0.2%) 0/388 (0%)
    Lipase increased 1/406 (0.2%) 0/388 (0%)
    Transaminases increased 1/406 (0.2%) 0/388 (0%)
    Metabolism and nutrition disorders
    Decreased appetite 9/406 (2.2%) 0/388 (0%)
    Dehydration 5/406 (1.2%) 1/388 (0.3%)
    Diabetes mellitus 1/406 (0.2%) 0/388 (0%)
    Diabetic ketoacidosis 1/406 (0.2%) 0/388 (0%)
    Electrolyte imbalance 1/406 (0.2%) 0/388 (0%)
    Hypercalcaemia 1/406 (0.2%) 1/388 (0.3%)
    Hyperglycaemia 2/406 (0.5%) 0/388 (0%)
    Hypochloraemia 0/406 (0%) 1/388 (0.3%)
    Hypoglycaemia 1/406 (0.2%) 0/388 (0%)
    Hypokalaemia 3/406 (0.7%) 1/388 (0.3%)
    Hypomagnesaemia 1/406 (0.2%) 0/388 (0%)
    Hyponatraemia 2/406 (0.5%) 2/388 (0.5%)
    Hypophosphataemia 0/406 (0%) 1/388 (0.3%)
    Malnutrition 1/406 (0.2%) 0/388 (0%)
    Type 1 diabetes mellitus 3/406 (0.7%) 0/388 (0%)
    Type 2 diabetes mellitus 0/406 (0%) 1/388 (0.3%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 1/406 (0.2%) 0/388 (0%)
    Arthritis 2/406 (0.5%) 0/388 (0%)
    Back pain 1/406 (0.2%) 0/388 (0%)
    Bone pain 0/406 (0%) 1/388 (0.3%)
    Fistula 1/406 (0.2%) 0/388 (0%)
    Myalgia 1/406 (0.2%) 0/388 (0%)
    Myositis 2/406 (0.5%) 0/388 (0%)
    Pain in extremity 2/406 (0.5%) 0/388 (0%)
    Pathological fracture 0/406 (0%) 1/388 (0.3%)
    Periarthritis 1/406 (0.2%) 0/388 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Malignant melanoma 0/406 (0%) 1/388 (0.3%)
    Myelodysplastic syndrome 1/406 (0.2%) 0/388 (0%)
    Plasma cell myeloma 1/406 (0.2%) 0/388 (0%)
    Tumour pain 0/406 (0%) 1/388 (0.3%)
    Nervous system disorders
    Cerebral haemorrhage 1/406 (0.2%) 0/388 (0%)
    Cerebral infarction 1/406 (0.2%) 0/388 (0%)
    Cerebrovascular accident 2/406 (0.5%) 3/388 (0.8%)
    Encephalitis autoimmune 1/406 (0.2%) 0/388 (0%)
    Encephalopathy 0/406 (0%) 1/388 (0.3%)
    Haemorrhage intracranial 1/406 (0.2%) 0/388 (0%)
    Haemorrhagic stroke 1/406 (0.2%) 0/388 (0%)
    Headache 2/406 (0.5%) 0/388 (0%)
    Migraine 1/406 (0.2%) 0/388 (0%)
    Myasthenia gravis 1/406 (0.2%) 0/388 (0%)
    Nervous system disorder 1/406 (0.2%) 0/388 (0%)
    Neuralgia 1/406 (0.2%) 0/388 (0%)
    Optic neuritis 1/406 (0.2%) 0/388 (0%)
    Seizure 0/406 (0%) 2/388 (0.5%)
    Syncope 1/406 (0.2%) 2/388 (0.5%)
    Tremor 1/406 (0.2%) 0/388 (0%)
    Product Issues
    Device dislocation 0/406 (0%) 1/388 (0.3%)
    Psychiatric disorders
    Anxiety 1/406 (0.2%) 1/388 (0.3%)
    Assisted suicide 1/406 (0.2%) 0/388 (0%)
    Confusional state 1/406 (0.2%) 0/388 (0%)
    Delirium 1/406 (0.2%) 1/388 (0.3%)
    Renal and urinary disorders
    Acute kidney injury 8/406 (2%) 3/388 (0.8%)
    Autoimmune nephritis 1/406 (0.2%) 0/388 (0%)
    Haematuria 1/406 (0.2%) 1/388 (0.3%)
    Haemorrhage urinary tract 1/406 (0.2%) 0/388 (0%)
    Hydronephrosis 1/406 (0.2%) 0/388 (0%)
    Nephrolithiasis 0/406 (0%) 1/388 (0.3%)
    Renal failure 3/406 (0.7%) 1/388 (0.3%)
    Renal injury 1/406 (0.2%) 0/388 (0%)
    Urinary tract obstruction 1/406 (0.2%) 0/388 (0%)
    Urogenital fistula 1/406 (0.2%) 1/388 (0.3%)
    Reproductive system and breast disorders
    Female genital tract fistula 3/406 (0.7%) 1/388 (0.3%)
    Metrorrhagia 1/406 (0.2%) 0/388 (0%)
    Uterine haemorrhage 1/406 (0.2%) 0/388 (0%)
    Vaginal haemorrhage 3/406 (0.7%) 0/388 (0%)
    Respiratory, thoracic and mediastinal disorders
    Aspiration 0/406 (0%) 1/388 (0.3%)
    Dyspnoea 2/406 (0.5%) 1/388 (0.3%)
    Dyspnoea exertional 0/406 (0%) 1/388 (0.3%)
    Epistaxis 2/406 (0.5%) 0/388 (0%)
    Pleural effusion 1/406 (0.2%) 1/388 (0.3%)
    Pneumonitis 3/406 (0.7%) 0/388 (0%)
    Pulmonary embolism 4/406 (1%) 5/388 (1.3%)
    Pulmonary hypertension 1/406 (0.2%) 0/388 (0%)
    Respiratory distress 0/406 (0%) 1/388 (0.3%)
    Respiratory failure 1/406 (0.2%) 3/388 (0.8%)
    Skin and subcutaneous tissue disorders
    Drug eruption 1/406 (0.2%) 0/388 (0%)
    Palmar-plantar erythrodysaesthesia syndrome 1/406 (0.2%) 0/388 (0%)
    Rash 1/406 (0.2%) 0/388 (0%)
    Rash macular 1/406 (0.2%) 0/388 (0%)
    Stasis dermatitis 1/406 (0.2%) 0/388 (0%)
    Stevens-Johnson syndrome 1/406 (0.2%) 0/388 (0%)
    Toxic skin eruption 1/406 (0.2%) 0/388 (0%)
    Umbilical haemorrhage 0/406 (0%) 1/388 (0.3%)
    Vascular disorders
    Aortic thrombosis 1/406 (0.2%) 0/388 (0%)
    Deep vein thrombosis 1/406 (0.2%) 2/388 (0.5%)
    Hypertension 17/406 (4.2%) 0/388 (0%)
    Hypotension 2/406 (0.5%) 0/388 (0%)
    Jugular vein thrombosis 1/406 (0.2%) 0/388 (0%)
    Pelvic venous thrombosis 0/406 (0%) 1/388 (0.3%)
    Thrombosis 1/406 (0.2%) 0/388 (0%)
    Vasculitis 1/406 (0.2%) 0/388 (0%)
    Other (Not Including Serious) Adverse Events
    Lenvatinib 20 mg + Pembrolizumab 200 mg Treatment of Physician's Choice: (TPC) Doxorubicin or Paclitaxel
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 404/406 (99.5%) 379/388 (97.7%)
    Blood and lymphatic system disorders
    Anaemia 105/406 (25.9%) 181/388 (46.6%)
    Leukopenia 28/406 (6.9%) 49/388 (12.6%)
    Lymphopenia 25/406 (6.2%) 30/388 (7.7%)
    Neutropenia 29/406 (7.1%) 124/388 (32%)
    Thrombocytopenia 43/406 (10.6%) 25/388 (6.4%)
    Endocrine disorders
    Hyperthyroidism 44/406 (10.8%) 4/388 (1%)
    Hypothyroidism 231/406 (56.9%) 3/388 (0.8%)
    Gastrointestinal disorders
    Abdominal pain 79/406 (19.5%) 52/388 (13.4%)
    Abdominal pain upper 53/406 (13.1%) 27/388 (7%)
    Constipation 104/406 (25.6%) 96/388 (24.7%)
    Diarrhoea 215/406 (53%) 75/388 (19.3%)
    Dry mouth 40/406 (9.9%) 11/388 (2.8%)
    Dyspepsia 27/406 (6.7%) 19/388 (4.9%)
    Gastritis 21/406 (5.2%) 2/388 (0.5%)
    Gastrooesophageal reflux disease 27/406 (6.7%) 8/388 (2.1%)
    Haemorrhoids 23/406 (5.7%) 7/388 (1.8%)
    Nausea 200/406 (49.3%) 178/388 (45.9%)
    Stomatitis 78/406 (19.2%) 46/388 (11.9%)
    Vomiting 145/406 (35.7%) 79/388 (20.4%)
    General disorders
    Asthenia 94/406 (23.2%) 93/388 (24%)
    Fatigue 132/406 (32.5%) 107/388 (27.6%)
    Malaise 25/406 (6.2%) 19/388 (4.9%)
    Mucosal inflammation 48/406 (11.8%) 38/388 (9.8%)
    Oedema peripheral 48/406 (11.8%) 35/388 (9%)
    Pyrexia 54/406 (13.3%) 26/388 (6.7%)
    Infections and infestations
    Nasopharyngitis 14/406 (3.4%) 24/388 (6.2%)
    Urinary tract infection 95/406 (23.4%) 38/388 (9.8%)
    Investigations
    Alanine aminotransferase increased 86/406 (21.2%) 19/388 (4.9%)
    Amylase increased 29/406 (7.1%) 5/388 (1.3%)
    Aspartate aminotransferase increased 80/406 (19.7%) 16/388 (4.1%)
    Blood alkaline phosphatase increased 50/406 (12.3%) 14/388 (3.6%)
    Blood bilirubin increased 22/406 (5.4%) 7/388 (1.8%)
    Blood cholesterol increased 34/406 (8.4%) 7/388 (1.8%)
    Blood creatinine increased 44/406 (10.8%) 10/388 (2.6%)
    Blood thyroid stimulating hormone increased 52/406 (12.8%) 1/388 (0.3%)
    Lipase increased 44/406 (10.8%) 8/388 (2.1%)
    Lymphocyte count decreased 17/406 (4.2%) 23/388 (5.9%)
    Neutrophil count decreased 22/406 (5.4%) 94/388 (24.2%)
    Platelet count decreased 50/406 (12.3%) 22/388 (5.7%)
    Weight decreased 138/406 (34%) 22/388 (5.7%)
    White blood cell count decreased 20/406 (4.9%) 60/388 (15.5%)
    Metabolism and nutrition disorders
    Decreased appetite 174/406 (42.9%) 82/388 (21.1%)
    Dehydration 21/406 (5.2%) 7/388 (1.8%)
    Hypercholesterolaemia 24/406 (5.9%) 7/388 (1.8%)
    Hyperglycaemia 36/406 (8.9%) 19/388 (4.9%)
    Hypertriglyceridaemia 51/406 (12.6%) 11/388 (2.8%)
    Hypoalbuminaemia 37/406 (9.1%) 18/388 (4.6%)
    Hypokalaemia 52/406 (12.8%) 26/388 (6.7%)
    Hypomagnesaemia 71/406 (17.5%) 26/388 (6.7%)
    Hyponatraemia 34/406 (8.4%) 16/388 (4.1%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 123/406 (30.3%) 31/388 (8%)
    Back pain 48/406 (11.8%) 29/388 (7.5%)
    Myalgia 71/406 (17.5%) 19/388 (4.9%)
    Pain in extremity 44/406 (10.8%) 21/388 (5.4%)
    Nervous system disorders
    Dizziness 42/406 (10.3%) 22/388 (5.7%)
    Dysgeusia 40/406 (9.9%) 27/388 (7%)
    Headache 99/406 (24.4%) 34/388 (8.8%)
    Neuropathy peripheral 16/406 (3.9%) 22/388 (5.7%)
    Psychiatric disorders
    Insomnia 33/406 (8.1%) 20/388 (5.2%)
    Renal and urinary disorders
    Dysuria 22/406 (5.4%) 11/388 (2.8%)
    Proteinuria 117/406 (28.8%) 11/388 (2.8%)
    Respiratory, thoracic and mediastinal disorders
    Cough 53/406 (13.1%) 51/388 (13.1%)
    Dysphonia 93/406 (22.9%) 2/388 (0.5%)
    Dyspnoea 44/406 (10.8%) 41/388 (10.6%)
    Epistaxis 31/406 (7.6%) 10/388 (2.6%)
    Oropharyngeal pain 22/406 (5.4%) 9/388 (2.3%)
    Skin and subcutaneous tissue disorders
    Alopecia 22/406 (5.4%) 120/388 (30.9%)
    Dry skin 28/406 (6.9%) 11/388 (2.8%)
    Palmar-plantar erythrodysaesthesia syndrome 86/406 (21.2%) 3/388 (0.8%)
    Pruritus 42/406 (10.3%) 12/388 (3.1%)
    Rash 61/406 (15%) 13/388 (3.4%)
    Vascular disorders
    Hypertension 250/406 (61.6%) 20/388 (5.2%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Eisai Medical Information
    Organization Eisai Inc.
    Phone 1-888-274-2378
    Email esi_oncmedinfo@eisai.com
    Responsible Party:
    Eisai Inc.
    ClinicalTrials.gov Identifier:
    NCT03517449
    Other Study ID Numbers:
    • E7080-G000-309
    • 2017-004387-35
    • MK3475-775
    First Posted:
    May 7, 2018
    Last Update Posted:
    Mar 29, 2022
    Last Verified:
    Dec 1, 2021