Zai Lab thinks two DLL3s might be better than one

Zai Lab’s DLL3-targeting ADC zocilurtatug pelitecan has long been in the shadow of Amgen’s approved bispecific Imdelltra, but now the smaller group is joining its rival, announcing puzzling plans to combine the two compounds. The company claims that the “complementary” dual-targeting strategy could lead to more and deeper responses, and address resistance pathways. However, toxicity will be closely watched: Imdelltra’s label carries a boxed warning of cytokine release syndrome, and the drug requires close monitoring, something Zai has previously talked up; meanwhile, there has been an interstitial lung disease death with a 2.4mg/kg dose of zoci-P. Under Wednesday’s clinical trial collaboration Amgen will sponsor a global phase 1b study in extensive-stage small-cell lung cancer. There are ongoing questions about Zai’s plan to pursue US accelerated approval of zoci-P in relapsed SCLC, given the full approval of Imdelltra here last year. Zai began the phase 3 Dllevate trial in this second and third-line (post-Imdelltra) disease last November, with co-primary endpoints of ORR and overall survival. However, it ditched plans to include Imdelltra in the control arm, instead limiting investigators to a choice of topotecan, Zepzelca or amrubicin. Zoci-P is licensed from MediLink, and uses the latter’s high-profile Tmalin linker-payload technology.