Paclitaxel-Avelumab for Angiosarcoma

Inclusion Criteria:

1. Signed written informed consent.

2. Male or female subjects aged ≥ 20 years.

3. Histologically or cytologically proven metastatic or locally advanced Angiosarcoma.

4. Inoperable Angiosarcoma

5. Chemo-naïve patient

6. ECOG performance status of 0 to 1 at trial entry and an estimated life expectancy ofat least 3 months.

7. Disease must be measurable with at least 1 measurable lesion by RECIST 1.1

8. Adequate hematological function defined by white blood cell (WBC) count ≥ 3 × 109/Lwith absolute neutrophil count (ANC) ≥ 1.5 × 109/L, lymphocyte count ≥ 0.5 × 109/L,platelet count ≥ 100 × 109/L, and hemoglobin ≥ 9 g/dL (may have been transfused).

9. Adequate hepatic function defined by a total bilirubin level ≤ 1.5 × the upper limitof normal range (ULN), an aspartate aminotransferase (AST), level ≤ 2.5 × ULN, and analanine aminotransferase (ALT) level ≤ 2.5 × ULN or, for subjects with documentedmetastatic disease to the liver, AST and ALT levels

≤ 5 × ULN.

10. Adequate renal function defined by an estimated creatinine clearance > 30mL/minaccording to the Cockcroft-Gault formula.

11. Highly effective contraception (that is, methods with a failure rate of less than 1%per year) for both male and female subjects if the risk of conception exists

Exclusion Criteria:

1. Concurrent treatment with a non-permitted drug (see Section 14)

2. Prior therapy with any antibody/drug targeting T cell co-regulatory proteins (immunecheckpoints) such as anti-PD-1, anti-PD-L1, or anti-cytotoxic T-lymphocyte antigen-4 (CTLA-4) antibody.

3. Concurrent anticancer treatment within 28 days before the start of trial treatment (e.g., cytoreductive therapy, radiotherapy [with the exception of palliative bonedirected radiotherapy], immune therapy, or cytokine therapy except for erythropoietin)

4. Major surgery within 28 days before the start of trial treatment (excluding priordiagnostic biopsy)

5. Use of hormonal agents within 7 days before the start of trial treatment.

6. Use of any investigational drug within 28 days before the start of trial treatment.

7. Subjects receiving immunosuppressive agents (such as steroids) for any reason shouldbe tapered off these drugs before initiation of the study treatment (with theexception of patients with adrenal insufficiency, who may continue corticosteroids atphysiologic replacement dose, equivalent to ≤ 10 mg prednisone daily). Steroids withno or minimal systemic effect (topical, inhalation) are allowed.

8. Previous malignant disease other than the target malignancy to be investigated in thistrial within the last 5 years with the exception of basal or squamous cell carcinomaof the skin or cervical carcinoma in situ.

9. Rapidly progressive disease (e.g., tumor lysis syndrome).

10. Active or history of central nervous system (CNS) metastases.

11. Receipt of any organ transplantation including allogeneic stem-cell transplantation.

12. Significant acute or chronic infections including, among others:

13. Known history of testing positive for human immunodeficiency virus (HIV) or knownacquired immunodeficiency syndrome (AIDS)

14. Positive test for HBV surface antigen and / or confirmatory HCV RNA (if anti-HCVantibody tested positive).

15. Active or history of any autoimmune disease (subjects with diabetes Type I, vitiligo,psoriasis, hypo- or hyperthyroid disease not requiring immunosuppressive treatment areeligible) or immunodeficiencies.

16. Known severe hypersensitivity reactions to monoclonal antibodies (Grade ≥ 3 NCI-CTCAEv4.0), any history of anaphylaxis, or uncontrolled asthma (i.e., 3 or more features ofpartly controlled asthma).

17. Persisting toxicity related to prior therapy Grade > 1 NCI-CTCAE v4.0, however sensoryneuropathy

≤ Grade 2 is acceptable.

16. Pregnancy or breast feeding.

17. Known alcohol or drug abuse.

18. Clinically significant (i.e., active) cardiovascular disease: cerebral vascularaccident/stroke (< 6 months prior to enrollment), myocardial infarction (< 6 monthsprior to enrollment), unstable angina, congestive heart failure (New York HeartAssociation Classification Class ≥ II), or serious uncontrolled cardiac arrhythmiarequiring medication.

19. All other significant diseases (e.g., inflammatory bowel disease), which, in theopinion of the investigator, might impair the subject's tolerance of trial treatment.

20. Any psychiatric condition that would prohibit the understanding or rendering ofinformed consent.

21. Legal incapacity or limited legal capacity.

22. Vaccination within 4 weeks of the first dose of avelumab and while on study isprohibited except for administration of inactivated vaccines (e.g. inactivatedinfluenza vaccines).