Amgen pushes on in Steap1

Amgen has cemented its position as the lead Steap1 player, taking xaluritamig into phase 3 in second-line metastatic castration-resistant prostate cancer. The next-furthest advanced asset here is AbbVie’s PSMA x Steap1 bispecific ADC ABBV-969, although this is well behind. While Steap1 competition is sparse, the CRPC scene is crowded, and Novartis’s Pluvicto could soon get the FDA nod in the pre-chemo setting. It’s notable that Amgen’s phase 3 trial, which will test xaluritamig against chemo or androgen receptor inhibitors, allows prior radioligand therapy. In phase 1 dose-expansion cohorts, presented at ESMO 2024, xaluritamig produced an ORR of 29% with the best-performing dose, 1.5mg every two weeks. In addition, 53% and 34% of patients achieved PSA50 and PSA90 respectively. On a cross-trial basis this looks in line with or slightly better than other hopefuls such as Johnson & Johnson’s anti-PMSA ADC ARX517; however, Janux’s PSMA-targeting T-cell engager JANX007 has impressed with an 83% PSA50 rate at a high dose. Xaluritamig’s toxicity will be closely watched: in phase 1, 66% of patients had grade 3 adverse events, 9% had grade 4, and 16% discontinued owing to treatment-related adverse events. Cytokine release syndrome and musculoskeletal side effects were particularly problematic.

The Steap1 pipeline

Source: OncologyPipeline.