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

Merkelcell.org Summary

Merkel cell carcinoma (MCC) is a rare and aggressive skin cancer that often spreads or comes back after treatment. For patients with advanced MCC, most are treated with drugs like immunotherapy, a drug that boosts the immune system to fight cancer. However, many patients do not respond well to immunotherapy alone, so researchers are looking for better treatment combinations.

The PANDORA trial is a new study testing whether combining immunotherapy with chemotherapy works better. This combination has helped people live longer in some other cancers, like lung and biliary tract cancers. Based on these studies, researchers are studying whether a similar combination could work for treating Merkel cell carcinoma.

The trial is taking place at multiple cancer centers and includes 35 patients with advanced MCC. Patients will receive pembrolizumab (an immunotherapy drug) along with cisplatin or carboplatin plus etoposide (chemotherapy drugs).

The goal of the trial is to see how many patients respond to the treatment. Other goals include tracking how long patients live, how long the cancer stays under control, and how the treatment affects quality of life. The study will also look for immune and genetic markers that may predict how well the treatment works. By combining two proven treatments, the PANDORA trial may lead to better results for patients with advanced MCC or reveal information about the biology of MCC treatment.

Abstract

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 [NCT 06086288] 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.