New drug combo shows promise for Hard-to-Treat cancers

NCT ID NCT04008797

Disease control Sponsor: Eisai Inc. Source: ClinicalTrials.gov ↗

First seen Jun 27, 2026 · Last updated Jun 27, 2026

Summary

This study tests a new drug called E7386 combined with other cancer drugs in people with advanced solid tumors, including endometrial, liver, and colorectal cancers. The goal is to find the safest and most effective dose and to see if the combination can shrink tumors. About 300 adults are taking part in this early-phase trial.

This is an AI summary of the original study and may miss details. Read our disclaimer.

Study facts

What this study's own registry entry says, in plain language.

Phase

Phase 1/2

Runs two stages together: safety and dose first, then whether the treatment works.

Participants

About 301 people

The number the study aims to enrol. It can still change while the study runs.

Started

Jul 2019

Expected to finish

Mar 2027

An estimate. End dates often move.

Lead sponsor

A company

The lead sponsor is a pharmaceutical, biotech, or medical-device company.

Who can take part

This study's own entry requirements. Only the study team can say for certain whether you qualify.

Ages

18 years and older

Sex

Anyone

Healthy volunteers

Not accepted

This study is not open to healthy volunteers. The entry requirements below say who it is open to.

Show the full entry requirements

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

Inclusion Criteria: 1. HCC part only: Participants with confirmed diagnosis of unresectable HCC with any of the following criteria: 1. Histologically or cytologically confirmed diagnosis of HCC, excluding fibrolamellar, sarcomatoid or mixed cholangio-HCC tumors 2. 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 2. Life expectancy of \>=12 weeks 3. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1 4. All AEs due to previous anti-cancer therapy have either returned to Grade 0 to 1 except for alopecia or up to Grade 2 peripheral neuropathy (renal/bone marrow/liver function should meet the inclusion criteria) 5. Adequate washout period before study drug administration: 1. Chemotherapy and radiotherapy: 3 weeks or 5 times the half-life, whichever is shorter 2. Any antitumor therapy with antibody: 4 weeks or more 3. Any investigational drug or device: 4 weeks or more 4. 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 6. Adequate controlled blood pressure (BP), renal function, bone marrow function, liver function, and serum mineral level 7. 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 * At least 1 lesion of \>=1.0 centimeter (cm) in the longest diameter for a non-lymph node or \>=1.5 cm in the short-axis diameter for a lymph node that is serially measurable according to RECIST 1.1 using computerized tomography (CT)/magnetic resonance imaging (MRI) * Lesions that have had external beam radiotherapy or loco-regional therapies such as radiofrequency ablation, or transarterial chemoembolisation (TACE)/ transarterial embolization (TAE) must show evidence of progressive disease based on RECIST 1.1 to be deemed a target lesion 8. For HCC participants only: Child-Pugh score A. Note: If Child-Pugh score 7 or more was observed during Screening or Baseline, the participant is ineligible and re-assessment of the Child-Pugh score is not permitted 9. For HCC participants only: Participants categorized to stage B (not amenable to locoregional therapy or refractory to locoregional therapy, and not amenable to a curative treatment), or stage C based on Barcelona Clinic Liver Cancer (BCLC) staging system 10. For HCC Subpart in Expansion Part only: prior systemic therapy for locally advanced or metastatic disease is as defined below a. Participants who have received only one prior line of immuno oncology (IO) based regimen and have progressed on or after prior treatment with IO based regimen, or IO ineligible participants who have received no prior systemic therapy. Participants who previously received lenvatinib treatment are ineligible 11. For CRC Subpart in Expansion Part only: participants must have received at least 2 prior regimens (not exceeding 4 prior regimens) or could not tolerate standard treatment and must have received the following prior therapies in the metastatic setting if approved and locally available (progressed on at least 1 prior regimen in the metastatic setting or could not tolerate standard treatment): Note: Adjuvant chemotherapy counts as prior systemic treatment if there is documented disease progression within 6 months of treatment completion Note: If a participant is determined to be intolerant to prior standard treatment, the participant must have received at least of 2 cycles of that therapy Note: Participants who have received oral tyrosine kinase inhibitor (example, regorafenib) are ineligible 1. Fluoropyrimidine, irinotecan and oxaliplatin with or without an anti-Vascular endothelial growth factor (VEGF) monoclonal antibody (mAb) (example, bevacizumab) Note: Capecitabine is acceptable as equivalent to fluoropyrimidine in prior treatment Note: Participants who have previously received fluoropyrimidine, oxaliplatin, and irinotecan as part of the same and only chemotherapy regimen, example, FOLFOXIRI or FOLFIRINOX, may be eligible after discussion with the Sponsor 2. Chemotherapy with anti- epidermal growth factor receptor (EGFR) mAb (cetuximab or panitumumab) for participants with rat sarcoma virus (RAS) (Kirsten rat sarcoma viral oncogene homolog \[KRAS)/ NRAS\]) wild type (WT) CRC Note: RAS (KRAS/NRAS) WT participants with right or left CRC lesions who may have not been treated with anti-EGFR mAb based on local guidelines are eligible 3. BRAF inhibitor (in combination with cetuximab ± binimetinib) for BRAF V600E mutated tumors 4. Immune checkpoint inhibitor for participants with microsatellite instability-high (MSI-H) CRC 12. For EC Subpart in Expansion Part only: Participants must have EC that has progressed after prior platinum-based chemotherapy and an anti-programmed cell death (ligand) 1 (PD-\[L\])1)-directed therapy for EC (participants ineligible for IO therapy who have progressed after prior platinum-based chemotherapy are eligible). Up to 3 prior systemic therapies, of which up to 2 for metastatic or locally advanced disease, are permitted Note: There is no restriction regarding prior hormonal therapies For Dose Optimization Part only: Participants must have EC that has progressed after prior platinum-based chemotherapy and an anti-PD-(L)1-directed therapy for EC. Up to 3 lines of prior therapy, regardless of setting, are allowed. Participants must be eligible for treatment with either single-agent paclitaxel or single-agent doxorubicin as determined by the investigator, with consideration of previous therapies received for EC. Note: Prior hormonal therapy and radiation are allowed and do not count as prior lines of therapy. Exclusion Criteria: 1. 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 (%) 2. 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 3. 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 4. 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 5. 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 6. Diagnosed with meningeal carcinomatosis 7. 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 8. Pulmonary lymphangitic involvement that results in pulmonary dysfunction requiring active treatment, including the use of oxygen 9. Any of bone disease/conditions as follows: * T-score of \< minus (-) 3.0 at the left or right total hip, left or right femoral neck or lumbar spine (L1-L4) as determined by dual energy x-ray absorptiometry (DXA) scan. Participants with T-score \<-2.5 to -3.0 can only be included if treatment with a bisphosphonate (example, zoledronic acid) or denosumab has been started at least 14 days and no more than 6 months prior to the first dose of study drug * Metabolic bone disease, such as hyperparathyroidism, Paget's disease or osteomalacia * Symptomatic hypercalcemia requiring bisphosphonate therapy * History of any fracture within 6 months prior to starting study drug * Bone metastasis requiring orthopedic intervention * Bone metastasis not being treated by bisphosphonate or denosumab. Participants may be included if treatment with bisphosphonate or denosumab has been started at least 14 days prior to the first dose of study drug. Participants with previous solitary bone lesions controlled with radiotherapy are eligible * History of symptomatic vertebral fragility fracture or any fragility fracture of the hip, pelvis, wrist or other location (defined as any fracture without a history of trauma or because of a fall from standing height or less) * Moderate (25% to 40% decrease in the height of any vertebrae) or severe (\>40% decrease in the height of any vertebrae) morphometric vertebral fracture at baseline 10. History of malignancy (except for original disease, or definitively treated melanoma in-situ, basal or squamous cell carcinoma of the skin, carcinoma in-situ \[example, bladder or cervix\]) within the past 24 months prior to the first dose of study drug 11. For HCC Subpart in Dose Escalation Part only: Participants who experienced discontinuation of lenvatinib, 2 or more dose reductions of lenvatinib required from initial dose level of this study due to its toxicity, or participants who experienced single dose reduction or consecutive \>=8 days dose interruption of lenvatinib within 60 days from the first dose, due to its toxicity. HCC Subpart in Expansion Part only: Participants who previously received lenvatinib treatment are ineligible. EC Subpart in Expansion Part only: Participants previously treated with lenvatinib who experienced discontinuation of lenvatinib due to toxicity, or dose reduction to less than 10 mg of lenvatinib due to toxicity within 60 days from the first dose. EC Dose Optimization Part only: Participants who previously received lenvatinib treatment are ineligible. 12. Bleeding or thrombotic disorders or use of anticoagulants requiring therapeutic International Normalized Ratio (INR) monitoring for HCC participants only (example, warfarin or similar agents). Treatment with low molecular weight heparin and factor X inhibitors is permitted. Treatment with antiplatelet agents is prohibited for HCC participants in Dose Escalation Part only 13. Gastrointestinal bleeding event or active hemoptysis (bright red blood of at least 0.5 teaspoon) within 3 weeks prior to the first dose of study drug 14. For HCC participants only: History of hepatic encephalopathy within 6 months prior to starting study drug 15. For EC Subpart in Expansion and Dose Optimization Parts only: carcinosarcoma (malignant mixed Mullerian tumor), endometrial leiomyosarcoma, and endometrial stromal sarcomas 16. Has preexisting \>=Grade 3 gastrointestinal or non-gastrointestinal fistula 17. Evidence of current Coronavirus disease 2019 (COVID-19) infection or ongoing unrecovered active sequelae of COVID-19 infection 18. Males who have not had a successful vasectomy (confirmed azoospermia) if their female partners meet the exclusion criteria above (that is, the female partners are of childbearing potential and are not willing to use a highly effective contraceptive method throughout the study period and after study drug discontinuation). No sperm donation is allowed during the study period and after study drug discontinuation 19. Has a known psychiatric or substance abuse disorder that would interfere with the participant ability to cooperate with the requirements of the study 20. Evidence of clinically significant disease (example, cardiac, respiratory, gastrointestinal, renal disease) that in the opinion of the investigator could affect the participant safety or interfere with the study assessments 21. Scheduled for major surgery during the study

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Conditions

The condition(s) this trial relates to.

colorectal cancer colorectal neoplasm endometrial carcinoma endometrium neoplasm hepatocellular carcinoma liver and intrahepatic bile duct neoplasm Liver Neoplasms neoplasm

As listed by the trial registrant

The condition terms exactly as the trial's registrant entered them.

Carcinoma, hepatocellular Colorectal neoplasms Endometrial neoplasms Liver neoplasms Neoplasms

Contacts and locations

Locations

AP-HP Universit de Paris, Port Royal

Paris, 75014, France
APHP Hospital Saint-Antoine

Paris, 75012, France
Asan Medical Center

Songpa-Gu, 05505, South Korea
Beijing Cancer Hospital

Beijing, 100142, China
CHU Amiens-Picardie (Hopital Sud)

Amiens, 80000, France
CHU Bordeaux

Bordeaux, 33075, France
CHU Cavale Blanche

Brest, 29200, France
CHU de LILLE - H pital HURIEZ

Lille, 59037, France
CHUM, Unit for Innovative Therapies

Montreal, Quebec, H2X 0C1, Canada
California Pacific Medical Center

San Francisco, California, 94066, United States
Cancer Hospital Chinese Academy of Medical Sciences, Shenzhen Center

Shenzhen, 518100, China
Cancer Hospital of Shandong First Medical University

Jinan, 250117, China
Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States
Centre Antoine Lacassagne

Nice, 6100, France
Centre Fran ois Baclesse

Caen, 14000, France
Centre Georges-Fran ois Leclerc

Dijon, 21000, France
Centre Hospitalier Universitaire (CHU) de Poitiers

Poitiers, 86000, France
Centre Hospitalier Universitaire de Bordeaux (CHU Bordeaux)(Hopitaux de Bordeaux) - Groupe hospitalier Sud - Hopital Haut-Levequ

Pessac, 33604, France
Centre Jean Perrin

Clermont-Ferrand, 63000, France
Centre L on B rard

Lyon, 69008, France
Chang Gung Medical Foundation - Kaohsiung Branch

Kaohsiung City, 83301, Taiwan
Chang Gung Medical Foundation - Linkou Branch

Taoyuan, 33305, Taiwan
Cl nica Universidad de Navarra

Madrid, 28027, Spain
Clinica Oncologica AOU (Azienda Ospedaliero Universitaria) delle Marche

Ancona, 60126, Italy
Eisai#1001

Chuo-ku, Tokyo, Japan
Eisai#1002

Kashiwa, Chiba, Japan
Eisai#1003

Sayama, Osaka, Japan
Eisai#1004

Chiba, Japan
Eisai#1005

Nagoya, Aichi-ken, Japan
Eisai#1006

Koto-ku, Tokyo, Japan
Eisai#1007

Kurume, Fukuoka, Japan
Eisai#1008

Matsuyama, Ehime, Japan
Eisai#1009

Hidaka, Saitama, Japan
Eisai#1010

Kawasaki, Kanagawa, Japan
Eisai#1011

Toyoake, Aichi-ken, Japan
Eisai#1012

Kamigyō-ku, Kyoto, Japan
Eisai#1013

Akashi, Hyōgo, Japan
Eisai#1014

Niigata, Japan
Eisai#1015

Minato-ku, Tokyo, Japan
Florida Cancer Specialists - East

West Palm Beach, Florida, 33401, United States
Florida Cancer Specialists - South

Sarasota, Florida, 34236, United States
Fondazione Policlinico Gemelli IRCCS

Rome, 00168, Italy
Fred Hutchinson/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States
Fudan University Cancer Center

Shanghai, 200032, China
Fujian Provincial Cancer Hospital

Fuzhou, 350014, China
Fundaci Privada Institut d Investigaci Oncol gica de Vall-Hebron (VHIO)

Barcelona, 08035, Spain
Grenoble University Hospital (Centre Hospitalier Universitaire Grenoble Alpes)

La Tronche, 38700, France
Gustave Roussy Institute (IGR)

Villejuif, 94805, France
H pital Beaujon

Clichy, 92110, France
H. Clinico San Carlos

Madrid, 28040, Spain
Hepatology, Hopital de la Croix-Rousse - 103 grande rue de la Croix-Rousse

Lyon, 69004, France
Hopital Europeen Georges-Pompidou (HEGP)

Paris, 75015, France
Hopital de la Croix Saint-Simon

Paris, 75020, France
Hospital Universitario 12 de Octubre

Madrid, 28041, Spain
Hospital Universitario de Ja n

Jaén, 23007, Spain
ICANs

Strasbourg, 67200, France
Insitute de Canc rologie de l'Ouest - Centre Ren Gauducheau

Saint-Herblain, 44800, France
Institut Curie - Centre de Recherche

Paris, 75005, France
Istituto Clinico Humanitas, Rozzano

Milan, 20159, Italy
John Muir Clinical Research

Walnut Creek, California, 94598, United States
Kansas City Research Institute

Kansas City, Missouri, 64131, United States
Korea University Guro Hospital

Guro-gu, 08308, South Korea
MD Anderson Cancer Center

Houston, Texas, 77030, United States
Mary Crowley Cancer Research

Dallas, Texas, 75230, United States
McGill University Health Centre

Montreal, Quebec, H4A 3J1, Canada
Medical University of South Carolina

Charleston, South Carolina, 29425, United States
Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States
MetroHealth Medical Center

Cleveland, Ohio, 44109, United States
Montefiore Medical Center (MMC) - Jack D. Weiler Hospital

The Bronx, New York, 10461, United States
National Cancer Center

Ilsandong-gu, 10408, South Korea
National Cheng Kung University Hospital

Tainan, 704, Taiwan
National Taiwan University Hospital

Taipei, 100, Taiwan
Odense University Hospital

Odense, 5000, Denmark
Pasadena Liver Center

Pasadena, California, 91105, United States
Peking Union Medical College Hospital

Beijing, 100730, China
Perlmutter Cancer Center- NYU Langone Health

New York, New York, 10016, United States
ProMedica Flower Hospital

Sylvania, Ohio, 43560, United States
Samsung Medical Center

Seoul, 06351, South Korea
Sanford Cancer Centre

Sioux Falls, South Dakota, 57106, United States
Seoul National University Bundang Hospital

Seongnamsi Bundang, 13620, 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
Sun Yan-sen University Cancer Center

Guangzhou, 510060, China
Sun Yat-Sen Memrial Hospital, Sun Yat-Sen University

Guangzhou, 510289, China
Sunnybrook Research Institute

Toronto, Ontario, M4N 3M5, Canada
Taichung Veterans General Hospital

Taichung, 40705, Taiwan
Taipei Veterans General Hospital

Taipei, 11217, Taiwan
Tennessee Oncology

Nashville, Tennessee, 37203, United States
The First Affiliated Hospital of Wenzhou Medical University

Wenzhou, 325000, China
The First Bethune Hospital of Jilin University

Changchun, 130021, China
The Tenth People's Hospital; Shanghai Tongji University

Shanghai, 200072, China
Tianjin Cancer Hospital

Tianjin, 300060, China
UAMS

Little Rock, Arkansas, 72205-7199, United States
UCLA University of California - Los Angeles

Santa Monica, California, 90404, United States
Uni. Of Miami- Sylvester Cancer Centre

Miami, Florida, 33136, United States
University Hospital A Coru a

A Coruña, 15006, Spain
University Of Mississippi Medical Center

Jackson, Mississippi, 39216, United States
University of California San Diego (UCSD) - Moores Cancer Center(All)

La Jolla, California, 92037, United States
University of Colorado Cancer Center - Anschutz Medical Campus

Aurora, Colorado, 80045, United States
University of Oklahoma Health Science Center

Oklahoma City, Oklahoma, 73104, United States
University of Texas Southwestern Medical

Dallas, Texas, 75390, United States
University of Ulsan College of Medicine - Asan Medical Center (AMC)

Songpa-gu, 05505, South Korea
Vanderbilt University Medical Center (VUMC) - Vanderbilt-Ingram Cancer Center (VICC) - Nashville

Nashville, Tennessee, 37232, United States
Women's Cancer Care - Covington, LA

Covington, Louisiana, 70433, United States
Yunnan Cancer Hospital

Kunming, 650118, China

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