Cemiplimab treatment in patients with locally advanced and metastatic secondary angiosarcomas

Dutch title

Behandeling met cemiplimab in patiënten met lokaal vergevorderd en/of uitgezaaid secundair angiosarcoom

Reference code

NCT04873375

Intervention model

Single group assignment

Full description

The purpose of this study is to evaluate the overall response rate after 24 weeks of cemiplimab treatment in patients with locally advanced or metastatic secondary angiosarcomas

Inclusion criteria

1. Adult patient aged ≥ 18 years
2. Histologically confirmed diagnosis of progressive unresectable locally advanced or metastatic secondary angiosarcoma
3. Patients in the first line of systemic treatment unfit for chemotherapy and patients in advanced lines of systemic treatment
4. Measurable disease per RECIST 1.1 or per physical examination / daylight photography (WHO Offset Publication No. 48) as determined by the investigator]
5. Tumour tissue material available (archival or recent tumour biopsy)
6. WHO ECOG 0-2
7. Hepatic function:
   • Total bilirubin ≤ 1.5 x ULN (if liver metastases: ≤ 3 x ULN).
   • Transaminases ≤ 3 x ULN (if liver metastases: ≤ 5 x ULN).
   • Patients with Gilbert’s Disease and total bilirubin up to 3x ULN may be eligible after communication with and approval from the medical monitor
   • Alkaline phosphatase ≤ 2.5 x ULN (if liver OR bone metastases ≤5 x ULN)
8. Renal function: serum creatinine ≤ 2 x ULN or estimated CrCl > 30 mL/min.
9. Creatine phosphokinase (CPK) (also known as CK [creatine kinase]) elevation ≤ grade 2
10. Bone marrow function:
    • Hemoglobulin ≥ 9.0 g/dL
    • ANC ≥ 1.5 x 109/L
    • Platelet count ≥ 75 x 109/L
11. Expected life expectancy of at least 3 months as judged by the investigator

Exclusion criteria

1. Ongoing or recent (within 5 years) evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments, which may suggest risk for irAEs. The following are not exclusionary: vitiligo, childhood asthma that has resolved, type 1 Diabetes mellitus, residual hypothyroidism that required only hormone therapy, or psoriasis that does not require systematic treatment
2. Prior treatment with immune checkpoint inhibitors
3. Continuous immunosuppressive corticosteroid treatment (doses > 10 mg prednisone daily or equivalent) within 4 weeks prior to the first dose of cemiplimab. Note: patients who require a brief course of steroids (e.g. as prophylaxis for imaging studies) are not excluded
4. Active uncontrolled infection requiring therapy, including infection with HIV, active infection with HBV or HCV
5. History of pneumonitis within the last 5 years
6. Untreated brain metastasis(es) that may be considered active
   • Note in clarification: Patients with previously treated brain metastases may participate provided that the lesion(s) is (are) stable (without evidence of progression for at least 6 weeks on imaging obtained in the screening period), and there is no evidence of new or enlarging brain metastases, and the patients do not require any immunosuppressive doses of systemic corticosteroids for management of brain metastasis(es) within 28 days of the first dose of cemiplimab
7. Patients with allergy or hypersensitivity to cemiplimab or to any of the excipients must be excluded. Specifically, because of the presence of trace components in cemiplimab, patients with allergy or hypersensitivity to doxycycline or tetracycline are excluded
8. History of documented allergic reactions or acute hypersensitivity reaction attributed to antibody treatments
9. Patients with a history of solid organ transplant (patients with prior corneal transplants may be allowed to enroll after discussion with and approval from the medical monitor)
10. Any anticancer treatment other than radiation therapy (chemotherapy, targeted systemic therapy, imiquimod, photodynamic therapy), investigational or standard of care, within 30 days of the initial administration of cemiplimab or planned to occur during the study period
11. Receipt of live vaccines (including attenuated) within 30 days of first study treatment
12. Prior use of PI3K-D inhibitors
13. Women of childbearing potential (WOCBP)*, or sexually active men, who are unwilling to practice highly effective contraception prior to the initial dose/start of the first treatment prior to the start of the first treatment, during the study, and for at least 6 months after the last dose.
14. Breastfeeding
15. Positive serum pregnancy test (a false positive pregnancy test, if demonstrated by serial measurements and negative ultrasound, will not be exclusionary, upon communication with and approval from the medical monitor)
16. Any other condition that might interfere with experimental treatment and the study procedures as judged by the investigator