Abstract A13: Clinical characteristics of responders to nivolumab plus ipilimumab (Nivo/Ipi) in metastatic uveal melanoma
Authors: Shephard Michael Paul , Glover Maura , Balmes Gener , Cain Suzanne , Vardeleon Anna , Mouton Rosalind , Posada Liberty , Simien Rinata , Hwu Patrick , Davies Michael , Yee Cassian , Wong Michael , Tawbi Hussein , Woodman Scott , Amaria Rodabe , Diab Adi , Glitza Isabella , Hwu Wen-Jen , Patel Sapna 
Published: June 2022

Abstract
In the U.S., prospective clinical trial data regarding nivolumab plus ipilimumab for metastatic uveal melanoma have yet to be reported. Here we present clinical data regarding responders to nivolumab plus ipilimumab that occurred in the context of a prospective clinical trial. NCT01585194 is an open-label, phase II study of nivolumab in combination with ipilimumab for the treatment of metastatic uveal melanoma. Patients with confirmed metastatic uveal melanoma received nivolumab 1 mg/kg followed by ipilimumab 3 mg/kg every 3 weeks for 4 doses, followed by up to 2 years of nivolumab maintenance. Response was evaluated using irRC beginning at week 12 and every 12 weeks thereafter. Responses were rare, but were seen in 3 patients, all female, with a mean age of 48. These subjects had hepatic M1b metastases (67%) and extrahepatic M1a metastasis (33%), and all three patients experienced a partial response at the first restaging, after 4 doses of Nivo/Ipi. Two additional patients, who came off study after two doses prior to response evaluation, one due to protocol-limiting hyperglycemia, and the other due to hyperuricemia and AKI, with M1b and M1a hepatic metastases, respectively, experienced partial responses. The first of these patients continued on additional Nivo/Ipi and developed a partial response 6 months after clinical trial initiation. The second patient never resumed additional treatment for metastatic disease. Her restaging scans 2 months after clinical trial initiation showed partial response; five months after initiation, her response continues with &gt;70% reduction in tumor burden. Responders to Nivo/Ipi had the following immune-mediated toxicities: endocrinopathy, vitiligo, diarrhea, pneumonitis, transaminitis, hyperglycemia, and nephritis. Baseline tissue analysis on one of the responders showed sheets of cytotoxic T lymphocytes invading the tumor in a biopsy specimen. Responses to Nivo/Ipi in metastatic uveal melanoma are not confined to extrahepatic sites. In our study, 4 of 5 (80%) responses were seen in hepatic metastases. Durability of responses and impact on overall survival remain to be seen, and tissue-based exploratory correlative studies are under way.
Citation Format: Michael Paul Shephard, Maura Glover, Gener Balmes, Suzanne Cain, Anna Vardeleon, Rosalind Mouton, Liberty Posada, Rinata Simien, Patrick Hwu, Michael Davies, Cassian Yee, Michael Wong, Hussein Tawbi, Scott Woodman, Rodabe Amaria, Adi Diab, Isabella Glitza, Wen-Jen Hwu, Sapna Patel. Clinical characteristics of responders to nivolumab plus ipilimumab (Nivo/Ipi) in metastatic uveal melanoma [abstract]. In: Proceedings of the AACR Special Conference on Melanoma: From Biology to Target; 2019 Jan 15-18; Houston, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(19 Suppl):Abstract nr A13.