Study of an Investigational Drug, E7386 Plus Lenvatinib in People with Endometrial Cancer after Chemotherapy and Immunotherapy

This study is an open-label, Phase 1b/2, randomized study of the oral medication E7386 plus the oral medication lenvatinib in people with endometrial cancer who had disease progression with platinum-based chemotherapy and anti-PD-(L)1 immunotherapy.

The study’s goal is to determine the safety and effectiveness of the drug E7386 in combination with lenvatinib in participants with advanced or recurrent endometrial cancer that has progressed after platinum-based chemotherapy and anti-PD-(L)1 immunotherapy.

The key objectives are to:

• Find the best dose of E7386 when used with lenvatinib.
• See how much E7386 adds to the effectiveness of the drug combination.
• Compare the combination of E7386 plus lenvatinib against standard chemotherapy used for recurrent endometrial cancer.

Approximately 120 study participants will be randomized to one of the following treatments:

• E7386 orally twice daily plus lenvatinib orally once daily
• Lenvatinib orally once daily
• Physician’s choice of chemotherapy (doxorubicin by intravenous injection every 3 weeks, or paclitaxel by intravenous injection weekly in a 3 weeks on/1 week off pattern)

The Dose Optimization part of the study involves the following:

• A Screening Period to determine your eligibility for the study. Consent to undergo a biopsy during screening is also required.
• A Treatment Period where you will receive your study treatment (treatment groups described above) and be carefully monitored for safety and changes to your disease. Treatment will continue until your disease gets worse, you have an unacceptable side effect, you change your mind and no longer wish to participate in the study, your physician determines that you should stop (eg. if they determine it is not safe or beneficial to continue treatment), or Eisai closes the study.
• A Follow-up Period where you will have a phone call every 3 months to assess your status.

Study procedures will include laboratory blood tests, urine analysis, vital signs, physical examinations, cardiac monitoring, scans to evaluate the extent of disease, bone scans to determine bone density.

Some requirements for participation include the following:

• You must be an adult (18 years or older) who has advanced or recurrent endometrial cancer and must be willing to undergo a tumor biopsy.
• You must have previously received treatment for endometrial cancer with platinum-containing chemotherapy and immunotherapy (chemotherapy and immunotherapy could have been given together or separately).
• You should have no more than 3 prior lines of treatment (if you have had previous treatment with radiation or hormonal therapy, these will not be counted).
• You must have recovered from any side effects that were caused by your previous treatments for endometrial cancer (exceptions are made for hair loss and some cases of peripheral neuropathy).
• You must have adequately controlled blood pressure with or without antihypertensive medications.
• You must have adequate kidney, liver, and bone marrow function.

Some exclusions for this trial include the following:

• You have previously received treatment with lenvatinib or E7386.
• You have central nervous system (CNS) metastases that have not been previously treated.
• You are unable to take oral medication or have uncontrolled nausea, diarrhea, or vomiting.
• Certain bone conditions (eg. a fracture within 6 months prior to starting study treatment).
• You have had another cancer within the 2 years prior to starting study treatment.

• Please refer to clinicaltrials.gov for further details on the inclusion and exclusion criteria for Study 102.