1519 Avelumab combined with regorafenib in solid tumors with tertiary lymphoid structures: a phase 2 REGOMUNE trial cohort

BackgroundMature tertiary lymphoid structures (mTLS) predict improved outcome in patients treated with immune checkpoint inhibitors (ICIs).1–5 However, a significant proportion of patients with TLS-positive tumors do not respond to ICI when used as a single agent and may therefore benefit from combination therapy. The multikinase inhibitor, regorafenib, deplete regulatory T cells, an immune population associated with resistance to ICI in TLS-positive tumors.5 We report the results of the PD-L1 inhibitor avelumab combined with regorafenib in patients with mTLS-positive advanced solid tumors.Methods‘Regomune’ is an open-label, multicenter phase II study assessing the combination of avelumab (10mg/kg IV every 14 days) with regorafenib (160 mg daily for 3 weeks in a 4-week cycle) in patients with advanced mTLS-positive solid tumors. The mTLS status was centrally assessed as previously described.1 5 All patients had confirmed progressive disease at inclusion, based on a central review of imaging. The primary efficacy endpoint was a 6-month non-progression rate using RECIST v1.1 based on blinded central review. 29 assessable patients were deemed necessary, and to meet the primary endpoint, at least 8 patients needed to be progression-free at 6 months.ResultsBetween January 2021 and July 2022, 132 patients (5 centers) underwent mTLS screening. Of these, 55 (41.7%) were identified as mTLS+, and 38 were included in the study. The top five histological subtypes were MSS colorectal cancer (15.8%), sarcoma (13.1%), oesogastric (10.5%), biliary tract (7.9%), and pancreatic cancer (7.9%). The most frequent grade 3/4 adverse events were palmar-plantar erythrodysesthesia syndrome (23.7%), maculo-papular rash (18.4%), fatigue, and oral mucositis (7.9% each). No treatment-related deaths were reported. Of the 34 patients assessed for efficacy, 16 (47%) showed tumor shrinkage, with 9 achieving a partial response (26.7%) and 7 having stable disease (20.6%). The median duration of response was 6 months. Twelve patients (comprising various tumor types including MSS colorectal cancer, small bowel carcinomas, biliary tract cancer, sarcomas, thyroid and gynecological tumors.) were progression-free at 6 months, marking the study’s primary endpoint achievement. The median progression-free survival and overall survival were 3.6 months and 8.6 months, respectively.ConclusionsThis is the pioneering histology-agnostic clinical trial employing mTLS as a biomarker for patient selection for