Selected Articles from This Issue

CD3 bispecific T cell engagers have demonstrated potent tumor cell lytic activity in many hematological malignancies, however the demonstration of activity in solid tumor indications is more challenging due to several issues including the availability of highly selective tumor targets that reduce “on-target, off-tumor activity”. ABBV-184 is a novel TCR/CD3 bispecific T cell engager, engineered for high affinity and high specificity recognition of an intracellular survivin-derived peptide bound to surface expressed class I MHC HLA-A*02:01, that based on its potent preclinical anti-tumor activity is an attractive clinical candidate for treatment of patients with either heme or solid tumor malignancies.

Nectin-4 is a protein overexpressed in many cancers and associated with poor prognosis. Existing nectin-4-targeting therapies have limited clinical benefit for non-bladder tumors. Here, Zhou and colleagues developed a novel antibody-drug conjugate (ADC), 9MW2821, that targets nectin-4 and delivers a potent cytotoxic agent, monomethyl auristatin E (MMAE), to cancer cells. 9MW2821 has a site-specific and stable conjugation technology that shows significant antitumor activity in preclinical tumor models, across a variety of cancer indications and is well tolerated in preclinical safety studies. These results suggest that 9MW2821 is a promising second-generation nectin-4-directed ADC that may improve the treatment of patients with advanced solid tumors.

HER2 is emerging as an important target across tumor types. Diperi and colleagues assessed discordance of HER2 status in patients with HER2-amplified or HER2-expressing solid tumors who underwent reevaluation of HER2 status centrally, most (81.4%) with a new biopsy. Discordance of HER2 status was common, especially for HER2 2+ tumors. Of 15 patients who were locally 2+. HER2 discordance was seen in 16 of 52 (30.8%) of patients with HER2 overexpression/amplification who underwent a new image-guided biopsy for testing. Repeat biomarker evaluation may have value when considering HER2-targeted therapy.