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
7. Melanoma cohort (Phase 2), participants must have:
8. Unresectable Stage III or Stage IV melanoma, not amenable to local therapy.
9. 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
10. 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)
11. HCC cohort (phase 2), participants must have:
12. Barcelona Clinic Liver Cancer (BCLC) Stage B (not amenable for transarterial chemoembolization [TACE]) or Stage C and Child Pugh class A
13. Has 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

1. 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
2. Participants with brain or subdural metastases, unless they have completed local therapy and have discontinued the use of corticosteroids for this indication for at least 4 weeks before starting treatment in this study
3. Any active infection requiring systemic treatment
4. Has severe hypersensitivity to study drugs and/or any of its excipients
5. Has 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.
6. Has an active autoimmune disease that has required systemic treatment in the past 2 years
7. Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis
8. Any bone disease/conditions as follows:
9. Osteoporosis with T-score <-2.5 by DXA scan
10. Metabolic bone disease, such as hyperparathyroidism, Paget's disease or osteomalacia
11. Symptomatic hypercalcemia requiring bisphosphonate therapy
12. History of any fracture within 6 months prior to starting study drug
13. History of symptomatic vertebral fragility fracture or any fragility fracture
14. Moderate or severe morphometric vertebral fracture at baseline.
15. Any condition requiring orthopedic intervention.
16. Bone metastases not being treated with a bisphosphonate or denosumab
17. 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
18. . Known to be human immunodeficiency virus (HIV) positive
19. . Received blood/platelet transfusion or G-CSF within 4 weeks before study entry
20. . For Melanoma only, participants with ocular melanoma are excluded
21. . For CRC only, participants are excluded if:
22. has a tumor that is microsatellite instability high (MSI H)/ DNA mismatch repair-deficient (dMMR) positive
23. has received prior treatment with anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
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