A Study of E7386 in Combination With Other Anticancer Drug(s) in Participants With Solid Tumor
An Open-label Study of E7386 in Combination With Other Anticancer Drug(s) in Subjects With Solid Tumors
3 other identifiers
interventional
301
10 countries
106
Brief Summary
The primary objective of this study is to assess the safety and tolerability and to determine the recommended Phase 2 dose (RP2D) of E7386 in combination with other anticancer drug(s), and to determine the optimal dose of E7386 in combination with lenvatinib in endometrial carcinoma (EC) (for EC Dose Optimization Part only).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Jul 2019
Longer than P75 for phase_1
106 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 24, 2019
CompletedFirst Posted
Study publicly available on registry
July 5, 2019
CompletedStudy Start
First participant enrolled
July 11, 2019
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 31, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
March 31, 2027
March 24, 2026
November 1, 2025
7.7 years
June 24, 2019
March 23, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (3)
Dose Escalation Part: Number of Participants with Dose-limiting Toxicities (DLTs)
DLTs will be defined as any of the events that are considered by the investigator to be at least possibly related to therapy with the study medication. Toxicity will be evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI CTCAE 5.0).
Cycle 0 (Cycle 0 length=6 or 7 days) up to Cycle 1 (Cycle 1 length=28 days)
Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
Up to 30 days after the last dose of study drug or before initiating post anti-cancer treatment (up to approximately 90 months)
Dose Optimization Part: Objective Response Rate (ORR) per RECIST 1.1 by Investigator Assessment
The ORR is defined as the percentage of participants with a best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR). The ORR will be assessed by investigator based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 for dose optimization part.
From first dose of study drug until PD, development of unacceptable toxicity, participant requests to discontinue, withdrawal of consent or study termination (up to approximately 90 months)
Secondary Outcomes (17)
Dose Escalation Part: Cmax: Maximum Observed Plasma Concentration for E7386
Day 1 to Day 8
Dose Escalation Part: Cmax: Maximum Observed Plasma Concentration for Lenvatinib
Day 8
Dose Escalation Part: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for E7386
Day 1 to Day 8
Dose Escalation Part: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Lenvatinib
Day 8
Dose Escalation Part: AUC: Area Under the Plasma Concentration Versus Time Curve for E7386
Day 1 to Day 8
- +12 more secondary outcomes
Study Arms (9)
Dose Escalation Part: HCC: E7386 QD Subpart + Lenvatinib
EXPERIMENTALParticipants with hepatocellular carcinoma (HCC) will receive E7386, once daily (QD) for 5 or 6 consecutive days followed by a period of time without treatment in Cycle 0 (6 or 7 days). Participants with HCC will receive E7386, QD in combination with lenvatinib 8 milligram (mg) (participants with body weight of less than \[\<\] 60 kilograms \[kg\]) or 12 mg (participants with body weight \>=60 kg), capsules, orally, QD in 28-day treatment cycles until PD, development of unacceptable toxicity, participant request to discontinue, withdrawal of consent, or termination of the study program.
Dose Escalation Part: HCC: E7386 BID Subpart + Lenvatinib
EXPERIMENTALParticipants with HCC will receive E7386, twice daily (BID) for 5 or 6 consecutive days in Cycle 0 (6 or 7 days). Participants with HCC will receive E7386, BID in combination with lenvatinib 8 mg (participants with body weight of \< 60 kg) or 12 mg (participants with body weight \>=60 kg) capsules, orally, QD in 28-day treatment cycles until PD, development of unacceptable toxicity, participant request to discontinue, withdrawal of consent, or termination of the study program.
Dose Escalation Part: Other ST: E7386 QD Subpart + Lenvatinib
EXPERIMENTALParticipants with solid tumor (ST) (except for HCC) will receive E7386, QD for 5 or 6 consecutive days followed by a period of time without treatment in Cycle 0 (6 or 7 days). Participants with ST (except for HCC) will receive E7386, QD in combination with lenvatinib 20 mg, capsules, orally, QD in 28-day treatment cycles until PD, development of unacceptable toxicity, participant request to discontinue, withdrawal of consent, or termination of the study program.
Dose Escalation Part: Other ST: E7386 BID Subpart + Lenvatinib
EXPERIMENTALParticipants with ST (except for HCC) will receive E7386, BID for 5 or 6 consecutive days in Cycle 0 (6 or 7 days). Participants with ST (except for HCC) will receive E7386, BID in combination with lenvatinib 20 mg, capsules, orally, QD in 28-day treatment cycles until PD, development of unacceptable toxicity, participant request to discontinue, withdrawal of consent, or termination of the study program.
Dose Expansion Part: HCC Subpart: Lenvatinib Only
EXPERIMENTALParticipants with HCC will receive lenvatinib 8 mg (participants with body weight of \<60 kg) or 12 mg (participants with body weight \>=60 kg), capsules, orally, QD in 28-day treatment cycles until PD, development of unacceptable toxicity, participant request to discontinue, withdrawal of consent, or termination of the study program
Dose Expansion Part: HCC Subpart: E7386 + Lenvatinib
EXPERIMENTALParticipants with HCC will receive lenvatinib 8 mg (participants with body weight of \<60 kg) or 12 mg (participants with body weight \>=60 kg), capsule, orally QD in combination with E7386 y, BID in 28-day treatment cycles until PD, development of unacceptable toxicity, participant request to discontinue, withdrawal of consent, or termination of the study program.
Dose Expansion Part: CRC Subpart: E7386 + Lenvatinib
EXPERIMENTALParticipants with colorectal cancer (CRC) will receive E7386, BID in combination with lenvatinib 20 mg, capsules, orally, QD in 28-day treatment cycles until PD, development of unacceptable toxicity, participant request to discontinue, withdrawal of consent, or termination of the study program.
Dose Expansion Part: EC Subpart: E7386 + Lenvatinib
EXPERIMENTALParticipants with endometrial cancer (EC) will receive E7386, BID in combination with lenvatinib 14 mg, capsules, orally, QD in 28-day treatment cycles until PD, development of unacceptable toxicity, participant request to discontinue, withdrawal of consent, or termination of the study program.
Dose Optimization Part: EC Participants
EXPERIMENTALParticipants with EC will be randomized to receive 2 different doses of E7386 in combination with lenvatinib capsule or lenvatinib capsule monotherapy in 28-days cycles, or treatment of physician's choice (TPC; doxorubicin in 21-day cycles or paclitaxel in 28-day cycles \[3 weeks on/1 week off\]), until PD, development of unacceptable toxicity, participant request to discontinue, withdrawal of consent, or termination of the study program.
Interventions
E7386 dosing.
Lenvatinib dosing.
Eligibility Criteria
You may qualify if:
- HCC part only:
- Participants with confirmed diagnosis of unresectable HCC with any of the following criteria:
- Histologically or cytologically confirmed diagnosis of HCC, excluding fibrolamellar, sarcomatoid or mixed cholangio-HCC tumors
- Clinically confirmed diagnosis of HCC according to American Association for the Study of Liver Diseases (AASLD) criteria, including cirrhosis of any etiology and/or chronic hepatitis B or C infection
- ST part only (except for HCC):
- Participants with histologically or cytologically confirmed diagnosis of solid tumor for which no alternative standard therapy or no effective therapy exists
- Life expectancy of \>=12 weeks
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1
- Adequate washout period before study drug administration:
- Chemotherapy and radiotherapy: 3 weeks or 5 times the half-life, whichever is shorter
- Any antitumor therapy with antibody: 4 weeks or more
- Any investigational drug or device: 4 weeks or more
- Blood/platelet transfusion or granulocyte colony-stimulating factor (G-CSF): 2 weeks or more Note: Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not had radiation pneumonitis
- Adequate controlled blood pressure (BP), renal function, bone marrow function, liver function, and serum mineral level
- At least one measurable lesion based on mRECIST (for HCC Subparts in Dose Escalation Part) or on RECIST 1.1 (for Other ST Subparts in Dose Escalation Part and all subparts in Expansion and Dose Optimization Parts) meeting following criteria
- +13 more criteria
You may not qualify if:
- Any of cardiac conditions as follows:
- Heart failure New York Heart Association (NYHA) Class II or above
- Prolongation of QT interval with Fridericias correction (QTcF) to greater than (\>) 480 millisecond (msec)
- Left ventricular ejection fraction (LVEF) less than (\<) 50 percent (%)
- Major surgery within 21 days or minor surgery (that is, simple excision) within 7 days prior to starting study drug. Participant must have recovered from the surgery related toxicities to less than Grade 2 Note: Adequate wound healing after major surgery must be assessed clinically, independent of time elapsed for eligibility
- Known to be human immunodeficiency virus (HIV) positive Note: the sponsor has evaluated whether to include participant with HIV. Given that this is the first combination study of E7386 with lenvatinib and that the main mechanism of action of E7386 is immunomodulation of the tumor microenvironment along with the fact that several anti-retroviral therapies have drug-drug interaction with cytochrome P450 3A (CYP3A) substrates, the sponsor has decided not to include these participants at the current time. However, further considerations will be made moving forward based on new emerging data Note: HIV testing is required at screening only when mandated by local health authority
- Participants with proteinuria on urine dipstick testing will undergo 24-hour urine collection for quantitative assessment of proteinuria. Participants with urine protein \>=1 gram per 24 hour will be ineligible
- Active infection requiring systemic treatment (Except for Hepatitis B and/or C \[HBV/HCV\] infection in HCC participants)
- In case of HBsAg (+) participants in HCC participants:
- Antiviral therapy for HBV is not ongoing
- HBV viral load is 2000 international unit per milliliter (IU/mL) or more at the Screening Period although antiviral therapy for HBV is ongoing
- Has dual active HBV infection (HBsAg (+) and/or detectable HBV deoxyribonucleic acid \[DNA\]) and HCV infection (anti-HCV Ab (+) and detectable HCV ribonucleic acid \[RNA\]) at study entry
- Diagnosed with meningeal carcinomatosis
- Participants with central nervous system metastases are only eligible if they have been previously treated and are radiologically stable, (that is, without evidence of progression for at least 4 weeks prior to first dose of study treatment by repeat imaging), clinically stable, and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment
- Pulmonary lymphangitic involvement that results in pulmonary dysfunction requiring active treatment, including the use of oxygen
- +22 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Eisai Inc.lead
Study Sites (106)
UAMS
Little Rock, Arkansas, 72205-7199, United States
University of California San Diego (UCSD) - Moores Cancer Center(All)
La Jolla, California, 92037, United States
Cedars-Sinai Medical Center
Los Angeles, California, 90048, United States
Pasadena Liver Center
Pasadena, California, 91105, United States
California Pacific Medical Center
San Francisco, California, 94066, United States
UCLA University of California - Los Angeles
Santa Monica, California, 90404, United States
John Muir Clinical Research
Walnut Creek, California, 94598, United States
University of Colorado Cancer Center - Anschutz Medical Campus
Aurora, Colorado, 80045, United States
Uni. Of Miami- Sylvester Cancer Centre
Miami, Florida, 33136, United States
Florida Cancer Specialists - South
Sarasota, Florida, 34236, United States
Florida Cancer Specialists - East
West Palm Beach, Florida, 33401, United States
Women's Cancer Care - Covington, LA
Covington, Louisiana, 70433, United States
University Of Mississippi Medical Center
Jackson, Mississippi, 39216, United States
Kansas City Research Institute
Kansas City, Missouri, 64131, United States
Perlmutter Cancer Center- NYU Langone Health
New York, New York, 10016, United States
Memorial Sloan Kettering Cancer Center
New York, New York, 10065, United States
Montefiore Medical Center (MMC) - Jack D. Weiler Hospital
The Bronx, New York, 10461, United States
MetroHealth Medical Center
Cleveland, Ohio, 44109, United States
ProMedica Flower Hospital
Sylvania, Ohio, 43560, United States
University of Oklahoma Health Science Center
Oklahoma City, Oklahoma, 73104, United States
Medical University of South Carolina
Charleston, South Carolina, 29425, United States
Sanford Cancer Centre
Sioux Falls, South Dakota, 57106, United States
Tennessee Oncology
Nashville, Tennessee, 37203, United States
Vanderbilt University Medical Center (VUMC) - Vanderbilt-Ingram Cancer Center (VICC) - Nashville
Nashville, Tennessee, 37232, United States
Mary Crowley Cancer Research
Dallas, Texas, 75230, United States
University of Texas Southwestern Medical
Dallas, Texas, 75390, United States
MD Anderson Cancer Center
Houston, Texas, 77030, United States
Fred Hutchinson/University of Washington Cancer Consortium
Seattle, Washington, 98109, United States
Sunnybrook Research Institute
Toronto, Ontario, M4N 3M5, Canada
CHUM, Unit for Innovative Therapies
Montreal, Quebec, H2X 0C1, Canada
McGill University Health Centre
Montreal, Quebec, H4A 3J1, Canada
Beijing Cancer Hospital
Beijing, 100142, China
Peking Union Medical College Hospital
Beijing, 100730, China
The First Bethune Hospital of Jilin University
Changchun, 130021, China
Fujian Provincial Cancer Hospital
Fuzhou, 350014, China
Sun Yan-sen University Cancer Center
Guangzhou, 510060, China
Sun Yat-Sen Memrial Hospital, Sun Yat-Sen University
Guangzhou, 510289, China
Cancer Hospital of Shandong First Medical University
Jinan, 250117, China
Yunnan Cancer Hospital
Kunming, 650118, China
Fudan University Cancer Center
Shanghai, 200032, China
The Tenth People's Hospital; Shanghai Tongji University
Shanghai, 200072, China
Cancer Hospital Chinese Academy of Medical Sciences, Shenzhen Center
Shenzhen, 518100, China
Tianjin Cancer Hospital
Tianjin, 300060, China
The First Affiliated Hospital of Wenzhou Medical University
Wenzhou, 325000, China
Odense University Hospital
Odense, 5000, Denmark
CHU Amiens-Picardie (Hopital Sud)
Amiens, 80000, France
CHU Bordeaux
Bordeaux, 33075, France
CHU Cavale Blanche
Brest, 29200, France
Centre Fran ois Baclesse
Caen, 14000, France
Centre Jean Perrin
Clermont-Ferrand, 63000, France
H pital Beaujon
Clichy, 92110, France
Centre Georges-Fran ois Leclerc
Dijon, 21000, France
Grenoble University Hospital (Centre Hospitalier Universitaire Grenoble Alpes)
La Tronche, 38700, France
CHU de LILLE - H pital HURIEZ
Lille, 59037, France
Hepatology, Hopital de la Croix-Rousse - 103 grande rue de la Croix-Rousse
Lyon, 69004, France
Centre L on B rard
Lyon, 69008, France
Centre Antoine Lacassagne
Nice, 6100, France
Institut Curie - Centre de Recherche
Paris, 75005, France
APHP Hospital Saint-Antoine
Paris, 75012, France
AP-HP Universit de Paris, Port Royal
Paris, 75014, France
Hopital Europeen Georges-Pompidou (HEGP)
Paris, 75015, France
Hopital de la Croix Saint-Simon
Paris, 75020, France
Centre Hospitalier Universitaire de Bordeaux (CHU Bordeaux)(Hopitaux de Bordeaux) - Groupe hospitalier Sud - Hopital Haut-Levequ
Pessac, 33604, France
Centre Hospitalier Universitaire (CHU) de Poitiers
Poitiers, 86000, France
Insitute de Canc rologie de l'Ouest - Centre Ren Gauducheau
Saint-Herblain, 44800, France
ICANs
Strasbourg, 67200, France
Gustave Roussy Institute (IGR)
Villejuif, 94805, France
Clinica Oncologica AOU (Azienda Ospedaliero Universitaria) delle Marche
Ancona, 60126, Italy
Istituto Clinico Humanitas, Rozzano
Milan, 20159, Italy
Fondazione Policlinico Gemelli IRCCS
Rome, 00168, Italy
Eisai#1005
Nagoya, Aichi-ken, Japan
Eisai#1011
Toyoake, Aichi-ken, Japan
Eisai#1002
Kashiwa, Chiba, Japan
Eisai#1008
Matsuyama, Ehime, Japan
Eisai#1007
Kurume, Fukuoka, Japan
Eisai#1013
Akashi, Hyōgo, Japan
Eisai#1010
Kawasaki, Kanagawa, Japan
Eisai#1012
Kamigyō-ku, Kyoto, Japan
Eisai#1003
Sayama, Osaka, Japan
Eisai#1009
Hidaka, Saitama, Japan
Eisai#1001
Chuo-ku, Tokyo, Japan
Eisai#1006
Koto-ku, Tokyo, Japan
Eisai#1015
Minato-ku, Tokyo, Japan
Eisai#1004
Chiba, Japan
Eisai#1014
Niigata, Japan
Korea University Guro Hospital
Guro-gu, 08308, South Korea
National Cancer Center
Ilsandong-gu, 10408, South Korea
Seoul National University Hospital
Jongno-gu, 03080, South Korea
Seoul St. Mary's Hospital
Seocho-Gu, 06591, South Korea
Severance Hospital (Yonsei University Medical Center)
Seodaemun, 03722, South Korea
Seoul National University Bundang Hospital
Seongnamsi Bundang, 13620, South Korea
Samsung Medical Center
Seoul, 06351, South Korea
Asan Medical Center
Songpa-Gu, 05505, South Korea
University of Ulsan College of Medicine - Asan Medical Center (AMC)
Songpa-gu, 05505, South Korea
University Hospital A Coru a
A Coruña, 15006, Spain
Fundaci Privada Institut d Investigaci Oncol gica de Vall-Hebron (VHIO)
Barcelona, 08035, Spain
Hospital Universitario de Ja n
Jaén, 23007, Spain
Cl nica Universidad de Navarra
Madrid, 28027, Spain
H. Clinico San Carlos
Madrid, 28040, Spain
Hospital Universitario 12 de Octubre
Madrid, 28041, Spain
Chang Gung Medical Foundation - Kaohsiung Branch
Kaohsiung City, 83301, Taiwan
Taichung Veterans General Hospital
Taichung, 40705, Taiwan
National Cheng Kung University Hospital
Tainan, 704, Taiwan
National Taiwan University Hospital
Taipei, 100, Taiwan
Taipei Veterans General Hospital
Taipei, 11217, Taiwan
Chang Gung Medical Foundation - Linkou Branch
Taoyuan District, 33305, Taiwan
Related Publications (2)
Mesropian A, Gris-Oliver A, Balaseviciute U, Potdar AA, Kimura T, Shen J, Torres-Marcen M, Abril-Fornaguera J, Pique-Gili M, Camell-Raventos D, Peix J, Fernandez-Martinez E, Huguet-Pradell J, Hernandez de Sande A, Keraite I, Esteban-Fabro R, Barcena-Varela M, Lindblad KE, Lujambio A, Guccione E, Thung S, Ikeda M, Kudo M, Sia D, Pinyol R, Llovet JM. E7386 Enhances Lenvatinib's Antitumor Activity in Preclinical Models and Human Hepatocellular Carcinoma. Clin Cancer Res. 2025 Dec 1;31(23):5037-5050. doi: 10.1158/1078-0432.CCR-25-0725.
PMID: 40986544DERIVEDEskander RN, Lee JY, Mirza MR, Lorusso D, MacKay H, Ray-Coquard I, Oaknin A, Gonzalez-Martin A, Hasegawa K, Corr BR, Wu X, Leary A, Hu T, Dutta L, Okpara CE, McKenzie J, Makker V. Randomized study evaluating optimal dose, efficacy, and safety of E7386 plus lenvatinib versus treatment of physician's choice in advanced/recurrent endometrial carcinoma previously treated with platinum-based chemotherapy and immune checkpoint inhibitors. Int J Gynecol Cancer. 2025 Sep;35(9):101812. doi: 10.1016/j.ijgc.2025.101812. Epub 2025 Apr 5.
PMID: 40318924DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 24, 2019
First Posted
July 5, 2019
Study Start
July 11, 2019
Primary Completion (Estimated)
March 31, 2027
Study Completion (Estimated)
March 31, 2027
Last Updated
March 24, 2026
Record last verified: 2025-11
Data Sharing
- IPD Sharing
- Will share
Eisai's data sharing commitment and further information on how to request data can be found on our website http://eisaiclinicaltrials.com/.