Conditions: Advanced Solid Tumors
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 30
Healthy volunteers: no

Brief summary:
This is a multicenter, open-label, Phase 1b/2 study which will be conducted in two parts: a Phase 1b part comprising a dose escalation and an expansion cohort; and a Phase 2 part which will comprise two cohorts. The purpose of the Phase 1b part is to identify the maximum tolerated dose (MTD) of E7050 and E7080 (lenvatinib) in combination in participants with unresectable advanced or metastatic solid tumors. In the subsequent Phase 1b expansion cohort and Phase 2 cohorts, additional participants with recurrent glioblastoma or unresectable Stage III or Stage IV melanoma and disease progression after prior systemic treatment will be enrolled to confirm the MTD (expansion cohort) and to further explore the clinical activity of E7050 and lenvatinib.

Detailed description:

Arms:
arm 1: Participants with unresectable advanced or metastatic solid tumors will receive E7050 in combination with lenvatinib to identify a Maximum Tolerated Dose. Dose escalation will begin at low doses of both E7050 and lenvatinib, and then gradually increase in future cohorts until a recommended combination dose is identified. A dose of E7050 and lenvatinib to be used in combination in Phase 2 will be recommended (RP2 dose). Participants will continue on treatment until disease progression, development of unacceptable toxicity, or withdrawal of consent. arm 2: Participants with recurrent glioblastoma (bevacizumab-naïve) will receive E7050 and lenvatinib at the RP2 dose. arm 3: Participants with recurrent glioblastoma (bevacizumab-naïve) will receive single agent lenvatinib 24 mg/day (1\*4 mg capsule + 2\*10 mg capsule) and at time of progression, E7050 add-on therapy at the RP2 dose (in combination with lenvatinib at dose of either the RP2 dose or the most recent dose of single agent lenvatinib, whichever is the lowest). arm 4: Participants with unresectable Stage III or Stage IV melanoma and disease progression after prior systemic treatment will receive E7050 and lenvatinib at the RP2 dose. arm 5: Participants with unresectable Stage III or Stage IV melanoma and disease progression after prior systemic treatment will receive single agent E7050 400 mg/day.

Interventions: intervention 1: Golvatinib intervention 2: Lenvatinib intervention 3: Lenvatinib
Intervention descriptions: intervention 1: Participants will receive E7050 50 mg and/or 100 mg tablets. E7050 will be administered orally once daily, in 28-day cycles. intervention 2: Participants will receive lenvatinib 1 mg and/or 4 mg and/or 10 mg capsules. Lenvatinib will be administered orally once daily, in 28-day cycles. intervention 3: Participants will receive lenvatinib 24 mg (1\*4 mg capsule + 2\*10 mg capsule) capsules. Lenvatinib will be administered orally once daily, in 28-day cycles.

Protocol document: