Pembrolizumab Plus Lenvatinib in Unresectable Cutaneous Angiosarcoma Patients

Cutaneous angiosarcoma is a rare cancer for which effective treatment has not been developed sufficiently. Still, because it often occurs in elderly people, the number of patients is increasing due to the aging population. Cutaneous angiosarcoma is difficult to completely remove by surgery, and recurrence and metastasis after surgery are not uncommon. Therefore, chemotherapy, radiation therapy, and a combination of these are currently widely used as treatments. Traditionally, the anticancer drug used for cutaneous angiosarcoma was mainly doxorubicin. In recent years, it has been reported that cancer shrank in 18% of patients after two months of paclitaxel administration in a clinical trial. Therefore, paclitaxel has become more commonly used for cutaneous angiosarcoma. Other options include anthracycline anticancer drugs and gemcitabine. However, even with these anticancer drugs (and radiation therapy), cutaneous angiosarcoma progresses quickly, and some reports have said that the 5-year survival rate is 9%. This study is planned to develop a safer and more effective treatment for cutaneous angiosarcoma and will include 38 participants. In this study, eligible participants will receive combination chemotherapy with 200 mg of pembrolizumab (injection liquid, once every 3 weeks) and 20 mg of lenvatinib (capsule, once daily) for up to approximately two years as protocol treatment unless the criteria for termination meet. Before, during, and after the protocol treatment, participants will undergo many examinations and evaluations, including blood tests, urine tests, and imaging tests (e.g., x-ray, CT scan, or MRI) to assess the safety and efficacy of the protocol treatment.

Inclusion Criteria: 1. Histologically diagnosed with cutaneous angiosarcoma. 2. Unresectable primary or metastatic disease. 3. No spinal metastases that require radiotherapy or surgical intervention. 4. No pericardial effusion, pleural effusion, or ascites that require treatment. 5. Age at enrollment: 18 years or older and 85 years or younger. 6. The most recent performance status score (ECOG) within 14 days prior to enrollment is 0 or 1. 7. A contrast-enhanced CT/MRI (head, neck, chest, abdomen, pelvis: slice thickness 5 mm or less) performed within 14 days prior to enrollment or have at least one measurable lesion that can be confirmed to be present on the surface of the body by visual inspection (for patients with contrast allergy or renal function deterioration, plain CT is allowed). 8. Cohort A (untreated patients): Cutaneous angiosarcoma without prior therapy. Cohort B (previously treated patients): Cutaneous angiosarcoma with prior therapy. 9. Have adequately controlled BP with or without antihypertensive medications (of 2 or less counted by components), defined as BP \=1,500/mm3 (2) Platelet count \>=10×104/mm3 (3) Hemoglobin \>=9.0 g/dL (4) AST \