Pembrolizumab plus lenvatinib in the treatment of unresectable cutaneous angiosarcoma: a study protocol of multicentre, open-label phase II study (NCCH2213, PLAS)

Introduction Cutaneous angiosarcoma (cAS) is a rare and aggressive malignancy with a poor prognosis. The disease most commonly occurs in older adults, with a peak age of 79–85 years and its incidence is expected to increase with population ageing. Standard treatments include radical surgery, radiation therapy, chemotherapy and combinations thereof. Paclitaxel is a commonly used systemic therapy; however, the 5-year overall survival (OS) rate remains approximately 32%. Therefore, the development of more effective treatments is urgently needed. Preclinical studies suggest that lenvatinib exerts immunomodulatory effects that may enhance the efficacy of programmed cell death protein 1/programmed cell death protein 1 inhibitors. Clinically, the combination of pembrolizumab and lenvatinib has been approved for uterine corpus cancer and renal cell carcinoma. We aim to evaluate the efficacy and safety of pembrolizumab plus lenvatinib in patients with unresectable cAS. Methods and analysis The PLAS study (NCCH2213) is a multicentre, open-label, phase II, investigator-initiated trial comprising two cohorts: cohort A (patients who have not been treated) and cohort B (patients who have previously received chemotherapy). Pembrolizumab (200 mg) is administered intravenously on day 1 of each 21-day cycle, and lenvatinib is administered orally at a dose of 20 mg daily on days 1–21 of each cycle. Treatment will continue for up to 35 cycles unless discontinuation criteria are met. The primary endpoint is the objective response rate, as assessed by central review. Secondary endpoints include objective response rate assessed by site investigators, progression-free survival, OS, disease control rate, duration of response, time to response and the incidence of adverse events and adverse drug reactions. An interim analysis will be conducted according to the Southwest Oncology Group two-stage design. The design emphasises feasibility in a rare cancer population and prioritises patient safety while pursuing therapeutic innovation. An independent Data and Safety Monitoring Committee and external reviewers will oversee safety and central tumour assessments. Ethics and dissemination This study (NCCH2213_protocol_en_ver.5.0) was approved by the institutional review boards of the National Cancer Center, Japan (number: NCCH2213). The results will be published in a peer-reviewed journal within 1 year of the study’s completion. Trial registration number NCT06673628.