Design and rationale of the phase II PANDORA trial: first line chemo-immunotherapy in advanced Merkel cell carcinoma.

Merkel cell carcinoma (MCC) is a rare neuroendocrine tumor of the skin with an aggressive behavior and high propensity for locoregional recurrence and metastasis. The therapeutic options in the metastatic disease are limited and are mainly based on immunotherapy or platinum-based doublets. Importantly, a significant proportion of patients experience resistance to single-agent immunotherapy highlighting the need for more active upfront combinations. The PANDORA trial [NCT06086288] is an open label, multicenter, phase II trial evaluating the activity and safety of pembrolizumab combined with cisplatin or carboplatin and etoposide as first line treatment in patients with advanced MCC. The primary endpoint is objective response rate (ORR). Secondary objectives include overall survival (OS), progression free survival (PFS) and duration of response (DOR). Exploratory objectives include identification of immune and molecular biomarkers and assessment of Health-Related Quality of Life of pembrolizumab plus cisplatin/carboplatin and etoposide in participants with advanced/metastatic MCC. We planned to enroll 35 patients according to the study design. The combination of immune checkpoint inhibitors and chemotherapy was associated with better outcomes compared to either treatment alone in several cancer thanks to a potential synergy. Moving from a biological and clinical rationale, PANDORA may impact on the therapeutic landscape of MCC. NCT06086288 (ClinicalTrials.gov).