A Study of E7386 in Combination With Other Anticancer Drug(s) in Participants With Solid Tumor

Inclusion Criteria:

1. HCC part only: Participants with confirmed diagnosis of unresectable HCC with any of the followingcriteria:

2. Histologically or cytologically confirmed diagnosis of HCC, excludingfibrolamellar, sarcomatoid or mixed cholangio-HCC tumors

3. Clinically confirmed diagnosis of HCC according to American Association for theStudy of Liver Diseases (AASLD) criteria, including cirrhosis of any etiologyand/or chronic hepatitis B or C infection ST part only (except for HCC): Participants with histologically or cytologically confirmed diagnosis of solid tumorfor which no alternative standard therapy or no effective therapy exists

4. Life expectancy of >=12 weeks

5. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1

6. All AEs due to previous anti-cancer therapy have either returned to Grade 0 to 1except for alopecia or up to Grade 2 peripheral neuropathy (renal/bone marrow/liverfunction should meet the inclusion criteria)

7. Adequate washout period before study drug administration:

8. Chemotherapy and radiotherapy: 3 weeks or 5 times the half-life, whichever isshorter

9. Any antitumor therapy with antibody: 4 weeks or more

10. Any investigational drug or device: 4 weeks or more

11. Blood/platelet transfusion or granulocyte colony-stimulating factor (G-CSF): 2weeks or more Note: Participants must have recovered from all radiation-relatedtoxicities, not require corticosteroids, and not had radiation pneumonitis

12. Adequate controlled blood pressure (BP), renal function, bone marrow function, liverfunction, and serum mineral level

13. At least one measurable lesion based on mRECIST (for HCC Subparts in Dose EscalationPart) or on RECIST 1.1 (for Other ST Subparts in Dose Escalation Part and allsubparts in Expansion and Dose Optimization Parts) meeting following criteria

• At least 1 lesion of >=1.0 centimeter (cm) in the longest diameter for anon-lymph node or >=1.5 cm in the short-axis diameter for a lymph node that isserially measurable according to RECIST 1.1 using computerized tomography (CT)/magnetic resonance imaging (MRI)

• Lesions that have had external beam radiotherapy or loco-regional therapiessuch as radiofrequency ablation, or transarterial chemoembolisation (TACE)/transarterial embolization (TAE) must show evidence of progressive diseasebased 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 morewas observed during Screening or Baseline, the participant is ineligible andre-assessment of the Child-Pugh score is not permitted

9. For HCC participants only: Participants categorized to stage B (not amenable tolocoregional therapy or refractory to locoregional therapy, and not amenable to acurative 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 advancedor metastatic disease is as defined below a. Participants who have received only one prior line of immuno oncology (IO) basedregimen and have progressed on or after prior treatment with IO based regimen, or IOineligible participants who have received no prior systemic therapy. Participantswho previously received lenvatinib treatment are ineligible

11. For CRC Subpart in Expansion Part only: participants must have received at least 2prior regimens (not exceeding 4 prior regimens) or could not tolerate standardtreatment and must have received the following prior therapies in the metastaticsetting if approved and locally available (progressed on at least 1 prior regimen inthe metastatic setting or could not tolerate standard treatment): Note: Adjuvant chemotherapy counts as prior systemic treatment if there isdocumented disease progression within 6 months of treatment completion Note: If aparticipant is determined to be intolerant to prior standard treatment, theparticipant must have received at least of 2 cycles of that therapy Note:Participants who have received oral tyrosine kinase inhibitor (example, regorafenib)are ineligible

12. Fluoropyrimidine, irinotecan and oxaliplatin with or without an anti-Vascularendothelial growth factor (VEGF) monoclonal antibody (mAb) (example,bevacizumab) Note: Capecitabine is acceptable as equivalent to fluoropyrimidinein prior treatment Note: Participants who have previously receivedfluoropyrimidine, oxaliplatin, and irinotecan as part of the same and onlychemotherapy regimen, example, FOLFOXIRI or FOLFIRINOX, may be eligible afterdiscussion with the Sponsor

13. Chemotherapy with anti- epidermal growth factor receptor (EGFR) mAb (cetuximabor panitumumab) for participants with rat sarcoma virus (RAS) (Kirsten ratsarcoma viral oncogene homolog [KRAS)/ NRAS]) wild type (WT) CRC Note: RAS (KRAS/NRAS) WT participants with right or left CRC lesions who may have notbeen treated with anti-EGFR mAb based on local guidelines are eligible

14. BRAF inhibitor (in combination with cetuximab ± binimetinib) for BRAF V600Emutated tumors

15. Immune checkpoint inhibitor for participants with microsatelliteinstability-high (MSI-H) CRC

16. For EC Subpart in Expansion Part only: Participants must have EC that has progressedafter 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 haveprogressed after prior platinum-based chemotherapy are eligible). Up to 3 priorsystemic therapies, of which up to 2 for metastatic or locally advanced disease, arepermitted Note: There is no restriction regarding prior hormonal therapies For DoseOptimization Part only: Participants must have EC that has progressed after priorplatinum-based chemotherapy and an anti-PD-(L)1-directed therapy for EC. Up to 3lines of prior therapy, regardless of setting, are allowed. Participants must beeligible for treatment with either single-agent paclitaxel or single-agentdoxorubicin as determined by the investigator, with consideration of previoustherapies received for EC. Note: Prior hormonal therapy and radiation are allowedand 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 7days prior to starting study drug. Participant must have recovered from the surgeryrelated toxicities to less than Grade 2 Note: Adequate wound healing after majorsurgery must be assessed clinically, independent of time elapsed for eligibility

3. Known to be human immunodeficiency virus (HIV) positive Note: the sponsor hasevaluated whether to include participant with HIV. Given that this is the firstcombination study of E7386 with lenvatinib and that the main mechanism of action ofE7386 is immunomodulation of the tumor microenvironment along with the fact thatseveral anti-retroviral therapies have drug-drug interaction with cytochrome P450 3A (CYP3A) substrates, the sponsor has decided not to include these participants at thecurrent time. However, further considerations will be made moving forward based onnew emerging data Note: HIV testing is required at screening only when mandated bylocal health authority

4. Participants with proteinuria on urine dipstick testing will undergo 24-hour urinecollection for quantitative assessment of proteinuria. Participants with urineprotein >=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 theScreening Period although antiviral therapy for HBV is ongoing

• Has dual active HBV infection (HBsAg (+) and/or detectable HBV deoxyribonucleicacid [DNA]) and HCV infection (anti-HCV Ab (+) and detectable HCV ribonucleicacid [RNA]) at study entry

6. Diagnosed with meningeal carcinomatosis

7. Participants with central nervous system metastases are only eligible if they havebeen previously treated and are radiologically stable, (that is, without evidence ofprogression for at least 4 weeks prior to first dose of study treatment by repeatimaging), clinically stable, and without requirement of steroid treatment for atleast 14 days prior to first dose of study treatment

8. Pulmonary lymphangitic involvement that results in pulmonary dysfunction requiringactive 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 rightfemoral neck or lumbar spine (L1-L4) as determined by dual energy x-rayabsorptiometry (DXA) scan. Participants with T-score <-2.5 to -3.0 can only beincluded if treatment with a bisphosphonate (example, zoledronic acid) ordenosumab has been started at least 14 days and no more than 6 months prior tothe first dose of study drug

• Metabolic bone disease, such as hyperparathyroidism, Paget's disease orosteomalacia

• 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. Participantsmay be included if treatment with bisphosphonate or denosumab has been startedat least 14 days prior to the first dose of study drug. Participants withprevious solitary bone lesions controlled with radiotherapy are eligible

• History of symptomatic vertebral fragility fracture or any fragility fractureof the hip, pelvis, wrist or other location (defined as any fracture without ahistory 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 atbaseline

10. History of malignancy (except for original disease, or definitively treated melanomain-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 experienceddiscontinuation of lenvatinib, 2 or more dose reductions of lenvatinib required frominitial dose level of this study due to its toxicity, or participants whoexperienced single dose reduction or consecutive >=8 days dose interruption oflenvatinib within 60 days from the first dose, due to its toxicity. HCC Subpart inExpansion Part only: Participants who previously received lenvatinib treatment areineligible. EC Subpart in Expansion Part only: Participants previously treated with lenvatinibwho experienced discontinuation of lenvatinib due to toxicity, or dose reduction toless than 10 mg of lenvatinib due to toxicity within 60 days from the first dose. EC Dose Optimization Part only: Participants who previously received lenvatinibtreatment are ineligible.

12. Bleeding or thrombotic disorders or use of anticoagulants requiring therapeuticInternational Normalized Ratio (INR) monitoring for HCC participants only (example,warfarin or similar agents). Treatment with low molecular weight heparin and factorX inhibitors is permitted. Treatment with antiplatelet agents is prohibited for HCCparticipants 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 priorto starting study drug

15. For EC Subpart in Expansion and Dose Optimization Parts only: carcinosarcoma (malignant mixed Mullerian tumor), endometrial leiomyosarcoma, and endometrialstromal sarcomas

16. Has preexisting >=Grade 3 gastrointestinal or non-gastrointestinal fistula

17. Evidence of current Coronavirus disease 2019 (COVID-19) infection or ongoingunrecovered active sequelae of COVID-19 infection

18. Males who have not had a successful vasectomy (confirmed azoospermia) if theirfemale partners meet the exclusion criteria above (that is, the female partners areof childbearing potential and are not willing to use a highly effectivecontraceptive method throughout the study period and after study drugdiscontinuation). No sperm donation is allowed during the study period and afterstudy drug discontinuation

19. Has a known psychiatric or substance abuse disorder that would interfere with theparticipant 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 couldaffect the participant safety or interfere with the study assessments

21. Scheduled for major surgery during the study