Comprehensive molecular diagnosis using whole genome and RNA sequencing of patients with advanced cancers as part of the NCT/DKTK MASTER program led to the identification of cancer-driving NRG1 fusions in a significant proportion of KRAS wild type pancreatic cancers. NRG1 rearrangements drive cancer development through ErbB receptor-mediated signaling pathway activation, as was shown when patients with NRG1-rearranged pancreatic cancer responded to ErbB inhibitor treatment.

NRG1 fusions are very rare but have now been detected in a broad range of malignant diseases. During a Phase II study, we plan to investigate the effectiveness of the pan-Erb inhibitor afatinib in advanced NRG1-rearranged malignant cancers once standard treatment has failed, at a number of centers in Germany. Patients with NRG1-positive tumors who meet the eligibility criteria can take part in the trial and will receive afatinib monotherapy.