ASTRO 2026: Nivolumab Plus Ipilimumab Shows Durable Responses in Advanced Merkel Cell Carcinoma
By: Wendy LaGrego
Posted: Friday, October 9, 2026
In a long-term analysis of a randomized phase II trial, nivolumab plus ipilimumab, with or without stereotactic body radiotherapy (SBRT), produced a 100% objective response rate among evaluable patients with advanced Merkel cell carcinoma who had not previously received immune checkpoint inhibitors. The findings were presented by Sungjune Kim, MD, PhD, of Mayo Clinic Florida in Jacksonville, and colleagues at the 2026 American Society for Radiation Oncology (ASTRO) Annual Meeting.
The investigators evaluated the efficacy and safety of combination immunotherapy as first-line treatment or following prior anti–PD-1/PD-L1 therapy, as well as the potential benefit of adding SBRT.
Study Details
This randomized, open-label phase II trial (NCT03071406) enrolled 50 adults with unresectable, recurrent, or stage IV Merkel cell carcinoma at two U.S. centers. Patients were randomly assigned 1:1 to receive nivolumab plus ipilimumab alone (arm A) or the doublet along with SBRT delivered at 24 Gy in three fractions (arm B). Eligible patients had at least two measurable lesions and available tumor tissue. Tumor response was assessed every 12 weeks.
The primary endpoint was objective response rate according to immune-related response criteria; secondary endpoints included progression-free survival, overall survival, local control of irradiated lesions, safety, and exploratory biomarkers. Outcomes were evaluated according to prior exposure to immune checkpoint inhibitors. Median follow-up was 54.5 months among patients who had not previously received immunotherapy and 10.8 months among those previously treated with immune checkpoint inhibitors.
Key Results
Among 22 evaluable patients without prior immune checkpoint inhibitor exposure, 11 (50%; 95% confidence interval [CI] = 31%–69%) achieved a complete response, and 11 (50%; 95% CI = 31%–69%) achieved a partial response, yielding an objective response rate of 100%. Median duration of response was 56.3 months (95% CI = 43.7 months to not estimable).
Among 26 patients previously treated with immune checkpoint inhibitors, 4 (15%; 95% CI = 5%–36%) achieved a complete response, and 4 (15%; 95% CI = 5%–36%) achieved a partial response. One patient (4%) had stable disease, and 17 (65%) experienced disease progression. Median duration of response was 10.8 months (95% CI = 4.9 months to not estimable).
Among immunotherapy-naive patients receiving nivolumab plus ipilimumab alone, median overall survival was 64.6 months (95% CI = 46.4 months to not estimable), and median progression-free survival was 54.9 months (95% CI = 36.6 months to not estimable). In the SBRT group, median overall survival was not reached, and median progression-free survival was 64.9 months. Although survival outcomes numerically favored the addition of SBRT, the difference was not statistically significant (P = .18).
Local control of irradiated lesions was 100% at 5 years. Grade 3 or higher treatment-related toxicity occurred in 44% of patients.
Exploratory biomarker analyses revealed increased levels of interleukins 2, 4, and 7, as well as CD8-positive T cells and natural killer cells, in peripheral blood samples from responders 2 weeks after the initial immunotherapy infusion. Responders also demonstrated increased clonality of the intratumoral T-cell receptor repertoire.
The investigators concluded that nivolumab plus ipilimumab produced durable responses and favorable survival outcomes among immunotherapy-naive patients with advanced or recurrent Merkel cell carcinoma. Although adding SBRT was associated with numerically longer progression-free and overall survival, the differences were not statistically significant.
