Potential Activity of Afatinib Among Patients With Advanced Solid Tumors With NGR1 Fusions

According to a small case series of patients enrolled in the phase 2 TAPUR study, afatinib showed potential activity among patients with advanced solid tumors harboring neuregulin 1 (NRG1) fusions.

The TAPUR study is a prospective phase 2 basket clinical trial enrolling patients with advanced solid tumors, multiple myeloma, or B-cell non-Hodgkin lymphoma. Patients were matched to one of 16 FDA-approved study drugs based on prespecified genomic inclusion and exclusion criteria. In this case series analysis, there were 4 patients from TAPUR included, all with advanced solid tumors with NRG1 fusions. Among these 4 patients, the primary tumor sites were colon (n = 2), lung (n = 1), and pancreas (n = 1). The primary end point was disease control (objective response or stable disease), with secondary end points including objective response, duration of response, duration of stable disease, and safety.

The patient with non-small cell lung cancer had a partial response, with a best change in target lesion from baseline of 31%, which lasted 24 weeks and progressed after 32 weeks on treatment. The time to death was 67 weeks with no adverse event or serious adverse events reported. Of the 2 patients with colorectal cancer, 1 patient had a stable disease, with a best change in target lesion of 17%, which lasted 136 weeks and then underwent resection and ended treatment. This patient is still alive and had not progressed at time of analysis, with no adverse events or serious adverse events reported. The other patient with colorectal cancer had a best response of progressive disease, with a best change in target lesion of 9%, and progressed at 8 weeks. The time to death was 35 weeks with no adverse events or serious adverse events reported. The patient with pancreatic ductal adenocarcinoma achieved stable disease, with a best change in target lesion of 9%, which lasted for 64 weeks. Time to death was 94 weeks with no adverse events or serious adverse events reported.

Study authors noted, “While results of this study are encouraging and align with prior studies, larger clinical trials of afatinib in these patient populations are needed to solidify these findings, despite the challenges due to the rarity of NRG1 fusions." They concluded, “Afatinib demonstrated promising activity in patients with advanced solid tumors with NRG1 fusions, including durable [disease control] warranting additional study.

Source:

Rodon J, Mangat PK, Grantham GN, et al. Afatinib in patients with solid tumors with neuregulin 1 (NRG1) fusions: A case series from the Targeted Agent and Profiling Utilization Registry (TAPUR) Study. ESMO Open. Published online: April 10, 2025. doi:10.1016/j.esmoop.2025.104545