A stratified phase I dose escalation trial of hypofractionated radiotherapy followed by ipilimumab in metastatic melanoma: long-term follow-up and final outcomes

• Published in: Oncoimmunology Vol. 10; no. 1; p. 1863631
• Main Authors: Maity, Amit, Mick, Rosemarie, Rengan, Ramesh, Mitchell, Tara C., Amaravadi, Ravi K., Schuchter, Lynn M., Pryma, Daniel A., Patsch, Dana M., Maity, Alisha P., Minn, Andy J., Vonderheide, Robert H., Lukens, John N.
• Format: Journal Article
• Language: English
• Published: United States Taylor & Francis 01.01.2021; Taylor & Francis Group
• Subjects: abscopal; CTLA-4; Follow-Up Studies; Humans; hypofractionated radiation; ipilimumab; Ipilimumab - therapeutic use; Melanoma - drug therapy; Neoplasms, Second Primary; Original Research; Progression-Free Survival; radiation; CTLA-4; hypofractionated radiation; abscopal; radiation; ipilimumab
• ISSN: 2162-402X; 2162-4011; 2162-402X
• DOI: 10.1080/2162402X.2020.1863631

We conducted a phase I dose-escalation trial of radiation with ipilimumab in patients with melanoma with ≥2 metastatic lesions. Here, we report the final full clinical analysis. Patients received RT (6 or 8 Gy x 2 or 3 doses) to a single lesion followed by 4 cycles of ipilimumab. The primary endpoint was maximum tolerated dose of RT, and secondary endpoint was response at non-radiated sites. Twenty-two patients with treatment-naïve (n = 11) or treatment-refractory (n = 11) Stage IV melanoma were enrolled. There were 31 treatment-related adverse events (AEs), of which 16 were deemed immune-related. Eleven patients had grade 3 AEs (no grade 4/5). There were no dose-limiting toxicities related to the radiation/ipilimumab combination. Five of 22 patients (22.7%, 95% CI 7.8-45.4%) had partial response as best response and three (13.6%) had stable disease. Median overall survival was 10.7 months (95% CI, 4.9 months to not-estimable) and median progression-free survival 3.6 months (95% CI, 2.9 months to 7.8 months). Seven patients were still alive at the time of last follow-up (median follow-up 89.2 months), most of whom received pembrolizumab after progression. Radiotherapy followed by ipilimumab was well tolerated and yielded a response rate that compares favorably to the objective response rate with ipilimumab alone. Furthermore, 32% of patients are long-term survivors, most of whom received pembrolizumab. Based on these results, the recommended dose that was used in subsequent Phase 2 trials was 8 Gy x 3 doses. Clinical Trial Registration: NCT01497808 ( www.clinicaltrials.gov )