A Study of E7386 in Combination With Pembrolizumab in Previously Treated Participants With Selected Solid Tumors

Open to people ages 18 years and up

1. Male or female, age >=18 years at the time of informed consent
2. Have a histologically or cytologically-documented, advanced (metastatic and/or unresectable) selected solid tumor for which prior standard systemic therapy has failed. Selected tumor types: melanoma (excluding uveal melanoma), CRC, HCC
3. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
4. Must have disease progression on current or since the last anticancer treatment
5. At least one measurable lesion by computer tomography (CT) or magnetic imaging resonance (MRI) based on RECIST 1.1
6. Adequate organ function and serum mineral level per blood work as confirmed by the investigator
7. Calcium (albumin-corrected) within normal range
8. Potassium within normal reference range
9. Magnesium less than or equal to (>=) 1.2 milligram per deciliter (mg/dL) or 0.5 millimoles per litre (mmol/L).
10. Melanoma cohort (Phase 2), participants must have:
11. Unresectable Stage III or Stage IV melanoma, not amenable to local therapy.
12. Received only 1 or, if known BRAF mut +ve, 2 lines of therapies prior to study enrollment and must have progressed on 1 prior BRAF inhibitor
13. No restriction with regards to PD-L1 and BRAF status
14. CRC cohort (Phase 2), participants must have received at least 2 prior systemic therapies in adjuvant and/or metastatic setting (not exceeding 4 lines of therapies in the metastatic setting, progressed on at least 1 prior regimen in the metastatic setting or could not tolerate standard treatment)
15. HCC cohort (Phase 2), participants must have:
16. 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 and Child-Pugh class A only.
17. Have received only 1 prior line of systemic therapy in the locally advanced or metastatic setting, and must have progressed on treatment with an anti-PD-1/L1 monoclonal antibodies (mAb) administered either as monotherapy, or in combination
18. . Must agree to take Vitamin D continuous supplementation as per local institutional guideline/ investigator's clinical discretion if their 25-hydroxyvitamin D levels are less than 10 nanogram per milliliter (ng/mL).

1. Have present or progressive accumulation of pleural, ascitic, or pericardial fluid requiring drainage or diuretic drugs within 2 weeks prior to study drug administration. The participant can receive diuretic drugs as needed per the treating physician. Consult with the sponsor if the participant has more than trivial/trace fluid accumulation.
2. Prior treatment with E7386 or prior therapy with anti-PD-1, anti-PD-L1, or anti PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (example, CTLA-4, OX 40, CD137) that was discontinued due to a Grade 3 or higher immune-related (ir)AE
3. Participants with central nervous system (CNS) metastases are not eligible. Participants with previously treated brain metastases may participate provided they are radiologically stable, that is, without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment
4. Any active infection requiring systemic treatment
5. Have severe hypersensitivity to study drugs and/or any of its excipients
6. Have a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
7. Have an active autoimmune disease that has required systemic treatment in the past 2 years
8. Have a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis
9. Any bone disease/conditions as follows:
10. Osteoporosis with T-score <-2.5 by DXA scan
11. Metabolic bone disease, such as hyperparathyroidism, Paget's disease or osteomalacia
12. Symptomatic hypercalcemia requiring bisphosphonate therapy
13. History of any fracture within 6 months prior to starting study drug
14. History of symptomatic vertebral fragility fracture or any fragility fracture
15. Moderate or severe morphometric vertebral fracture at baseline.
16. Any condition requiring orthopedic intervention.
17. Bone metastases not being treated with a bisphosphonate or denosumab
18. . Active viral hepatitis (B or C) as demonstrated by positive serology for participants with melanoma and CRC. Dual active hepatitis B virus (HBV) infection and hepatitis C virus (HCV) infection at study entry for participants with HCC
19. . Known to be human immunodeficiency virus (HIV) positive
20. . Received blood/platelet transfusion or G-CSF within 4 weeks before study entry
21. . For Melanoma only, participants with ocular melanoma are excluded. Note: Participants with mucosal melanoma will not exceed 20% of the enrolled participants in melanoma cohort in Phase 2.
22. . For CRC only, participants are excluded if:
23. have a tumor that is microsatellite instability high (MSI H)/ DNA mismatch repair-deficient (dMMR) positive
24. . For HCC only, participants are excluded if:
25. clear invasion to bile duct or portal vein invasion of Vp4
26. symptomatic gastric or esophageal varices per Investigator's clinical judgement
27. history of hepatic encephalopathy within 6 months prior to starting study drug