Zai argues the case for combos

Zai Lab is taking two shots at combining its anti-DLL3 ADC zocilurtatug pelitecan with molecules having the same target, and on Thursday investors learned a little more about this unusual strategy. Zoci-P is “an ideal backbone” for combinations with DLL3-targeting T-cell engagers, Zai said on its first-quarter financials call, having to date struck two clinical trial collaborations to investigate such an approach: first with Amgen’s Imdelltra, and then with Boehringer Ingelheim’s obrixtamig. The rationale, at least preclinically, is that zoci-P’s cytotoxic ADC mechanism can rapidly reduce tumour volume, and a T-cell engager can then activate T cells, with such a combo having the potential to deepen and broaden responses with minimal toxicity overlap. Zai also revealed more detailed plans for the obrixtamig combo study, which has yet to be listed on clinicaltrials.gov. Just like the Imdelltra combo Dellphi-313 trial, this will include a triplet whereby the two anti-DLL3 molecules are tested with or without PD-L1 blockade; in the case of Dellphi-313 the anti-PD-L1 is AstraZeneca’s Imfinzi, while for the obrixtamig trial it will be Roche’s Tecentriq. Zai said it was also continuing to pursue additional combination approaches. Trials combining zoci-P with an anti-DLL3 T-cell engagerStudyDoublet comboTriplet comboDellphi-313≥2nd-line SCLC1st-line SCLCZocilurtatug pelitecan + ImdelltraZocilurtatug pelitecan + Imdelltra + ImfinziUnnamedPoorly differentiated NECs1st-line SCLCZocilurtatug pelitecan + obrixtamigZocilurtatug pelitecan + obrixtamig + TecentriqNote: NECs=neuroendocrine carcinomas. Source: Zai Lab presentation.