Sungjune Kim, MD, PhD, Moffitt Cancer Center, Tampa, Florida, discusses results from a randomized phase 2 trial exploring first-line combination therapy with nivolumab and ipilimumab with or without stereotactic body radiation therapy for patients with advanced Merkel cell carcinoma.

The findings from this study were presented at the 2022 European Society for Medical Oncology (ESMO) Congress in Paris, France.

Transcript:

My name is Sungjune Kim. I'm an associate member and the director of Radiation Oncology Translational Research at the Moffitt Cancer Center and Research Institute. We've recently completed a randomized phase 2 trial of nivolumab plus ipilimumab versus nivolumab plus ipilimumab and radiation in advanced stage Merkel cell carcinoma. I'm here to give a presentation at the 2022 ESMO Congress in Paris.

To give a brief background on Merkel cell carcinoma, it's one of the most aggressive but rare cutaneous malignancies. It has historically been refractory to chemotherapy, and in recent years there's been a change in paradigm in the management of Merkel cell carcinoma with the advent of cancer immunotherapy. Currently, the standard care for medical cell carcinoma is single-agent PD-1 blockade. The FDA approved avelumab and pembrolizumab in 2016 for treatment of advanced stage Merkel cell carcinoma. The response rate to single-agent PD-1 blockade ranges from 33% to 58%, which is outstanding, but we wanted to improve the response rate even further and wanted to identify strategies to treat the patients who fail on this first-line immunotherapy.

We designed a 2 experimental arm randomized phase 2 trial comparing nivolumab-ipilimumab versus nivolumab, ipilimumab, and stereotactic body radiation therapy. We are trying to test 2 different questions. One would be whether a CTRA-4 blockade with ipilimumab can enhance the responses to nivolumab, which is a PD-1 blocker, and to see whether the immunogenic effects of stereotactic body radiation therapy can further improve cancer immunotherapy. We accrued about 50 patients in total, 25 patients in Arm A and 25 patients in Arm B. Patients in Arm A were treated with nivolumab at 240 mg every 2 weeks and ipilimumab 1 mg/kg body weight every 6 weeks. Arm B were treated with the same cancer immunotherapeutic agents plus stereotactic body radiation therapy to 24 Gy in 3 fractions, delivered during week 2.

The primary endpoint was objective response rate (ORR), and the secondary endpoints were progression-free survival (PFS), overall survival (OS), and local control of the irradiated lesions, as well as a few biomarker-driven exploratory endpoints. In terms of outcome, we've observed an outstanding response to nivolumab and ipilimumab combination among the patients who have never received cancer immunotherapy. When nivolumab-ipilimumab was given as a first-line agent, the response rate was 100%, and 41% of the patients also had complete responses. The responses are quite durable, the median duration of response has not been reached yet.

With 14.6 months of median follow-up, we've had 2 failures among 22 patients, which is basically 9% failure after initial responses. Among the patients who have previously progressed on single-agent PD-1 blockade, the responses were not as spectacular. 31% of the patients we were able to salvage with nivolumab-ipilimumab. The durability of responses was not as optimal either because half of the patients did end up failing after the initial responses. In terms of survival for immune checkpoint inhibitor-naïve population who have never received immunotherapy previously, the median survival for both PFS and OS have not been reached. For the patients who are refractory to single-agent PD-1 blockade, there was a median progression-free survival of approximately 3 months, and approximately 10 to 11 months of median overall survival was noted.

In terms of toxicity profiles, we observed approximately 36% of the patients with grade 3 or 4 toxicities, which is very similar to what was observed with prior randomized phase 3 trials in non-small cell lung cancer and mesothelioma. Basically, the toxicity profiles were manageable.

In conclusion, we've observed outstanding overall response rate for first-line nivolumab-ipilimumab delivery to Merkel cell carcinoma, patients with advanced disease, and we were able to salvage 31% of the patients who have previously progressed on single-agent PD-1 blockade. So nivolumab-ipilimumab can be considered for both our first-line and salvage setting for advanced Merkel cell carcinoma.

Source:

Kim S, Wuthrick E, Blakaj DM, et al. Combined nivolumab and ipilimumab with or without stereotactic body radiation therapy for advanced Merkel cell carcinoma. Presented at European Society for Medical Oncology Congress; September 9-13, 2022; Paris, France. Abstract LBA42.