Neuregulin 1 (NRG1) fusion proteins, which occur in many tumor types, bind HER3 and induce its dimerization with other HER/ERBB kinases, thereby promoting downstream oncogenic signaling and tumorigenesis. Because targeting HER2 and/or HER3 has been shown to be effective in NRG1-rearranged tumor models, Schram, Odintsov, and colleagues investigated zenocutuzumab, a HER2xHER3 bispecific antibody, in NRG1-rearranged tumors. In preclinical models of lung, breast, pancreas, and ovarian NRG1-rearranged tumors, zenocutuzumab reduced cell growth and HER3 and AKT phosphorylation and induced apoptosis. Three patients with NRG1 fusion–positive metastatic cancers were treated with zenocutuzumab and had a partial response, supporting its ongoing clinical evaluation in NRG1 fusion–positive cancers.

See article, p. 1233.

PD-1/PD-L1 blockade reportedly synergizes with agonists targeting the costimulatory molecule 4-1BB on primed CD8+ T cells. Muik and colleagues report the preclinical characterization and phase I results of GEN1046, a bispecific antibody designed to elicit an antitumor...

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