Afatinib in patients with solid tumors with neuregulin 1 (NRG1) fusions: a case series from the Targeted Agent and Profiling Utilization Registry (TAPUR) Study

Background: TAPUR is a phase II basket trial evaluating the antitumor activity of commercially available targeted agents in patients with advanced cancer and targetable genomic alterations. Results of four patients with various tumors with NRG1 fusions treated with afatinib are reported. Patients and methods: Eligible patients had advanced cancer, measurable disease (RECIST), Eastern Cooperative Oncology Group performance status 0-2, adequate organ function, tumors with NRG1 fusions, and no standard treatment options. The primary endpoint was disease control (DC), defined as objective response (OR) or stable disease (SD) of at least 16 weeks’ duration (SD16+). Secondary endpoints included OR, duration of response, duration of SD, and safety. Results: Four patients were enrolled from February 2020 to July 2021; all had solid tumors [colorectal cancer (n = 2), non-small-cell lung cancer (n = 1), and pancreatic adenocarcinoma (n = 1)] with an NRG1 fusion. All patients were evaluable for efficacy. One partial response and two SD16+ were observed. One patient was still alive as of October 2024 with SD of 134 weeks’ duration. No patients had a drug-related grade 3-5 adverse event (AE) or serious AE. Conclusion: Though the sample size was small, afatinib demonstrated promising activity in patients with advanced solid tumors with NRG1 fusions, including durable DC warranting additional study.