An Open-Label Phase 1b Study of E7386 in Combination With Other Anticancer Drug(s) in Subjects With Solid Tumors

E7386 inhibits beta-catenin and prevents the interaction of beta-catenin with its transcriptional coactivator, CREB (cAMP response element-binding) binding protein (CBP). This prevents binding of beta-catenin/CBP to WRE (Wnt-responsive element) and inhibits the activation of transcription of a wide range of target genes of Wnt/beta-catenin signaling, thereby preventing gene expression of many Wnt-related, pro-survival proteins and suppressing tumor cell growth.

In this study, the sponsor and investigators want to learn:

• How much of the study drug can be given with an acceptable level of side effects
• The effects of the study drug (good and bad)
• much of the study drug is absorbed into the blood and how fast it is removed
• How the study drug is acting on your body
• If research tests can be used in the future to predict who will benefit from E7386

This is a dose escalation/expansion study. Dose escalation means that the amount of the study given will be increased in each group of research participants, to find the most appropriate dose for further study. Dose expansion means a larger number of people receive the study drug dose determined to be appropriate in the dose escalation part of the study. You are being asked to take part in the dose expansion part of the study.

Only research participants who have hepatocellular (liver) carcinoma (HCC), colorectal cancer (CRC) or endometrial cancer (EC) will participate in the dose expansion portion of the study. Participants who have HCC will be randomly assigned 2:1 to receive the study drug in combination with Lenvatinib or Lenvatinib alone. The assignment is random, similar to the roll of a die.

It is not known whether the study regimen is better, the same as, or worse than the usual treatment (called “standard of care” therapy) given to people with this disease who are not taking part in a research study. For this reason, some HCC research participants will receive the study regimen (the study drug in combination with Lenvatinib) and some will receive the standard of care therapy (Lenvatinib alone). This will allow study doctors to compare the benefits and side effects of the two regimens.

Participants with CRC and EC will receive the study drug in combination with Lenvatinib.

The study will be conducted in four phases, Pre- Study Treatment Phase, Study Treatment Phase, Follow-up Phase and Extension Phase. The Pre-Study Treatment phase will include a screening period and a baseline/randomization period. The screening phase will last 28 days and may involve 2-3 clinic visits, to determine if you are eligible to enter the Study Treatment Phase. Baseline/randomization will last about 3 days to confirm your eligibility.

For the Study Treatment Phase, the study regimen will be given in cycles.  Each cycle is 28 days.

The study drug will be taken as tablets by mouth with water every 12 hours regardless of food intake at the same time every day. Lenvatinib will be taken as capsules by mouth once per day at the same time every day.