BI 905711 (TRAILR2/CDH17 bispecific) shows biomarker apoptosis but only stable disease in refractory GI cancers

BI 905711 is a TRAILR2/CDH17 bispecific antibody designed to trigger extrinsic apoptosis signaling in CDH17+ GI tumors; in Phase I monotherapy dose escalation/expansion (NCT04137289) in advanced refractory GI cancers (n=110; 80% CRC; median 3 prior lines), no DLTs were seen, MTD was not reached, 48.2% had TRAEs (most commonly nausea 16.4%), and among 104 response-evaluable patients the best signal was stable disease in 22.1% (no RP2D determined). In the separate Phase I combination study (NCT05087992) in CRC (n=12), BI 905711 at an RDE of 0.6mg/kg plus biweekly FOLFIRI + bevacizumab produced 91.7% stable disease with 2 DLTs and 91.7% TRAEs (notably appetite loss 33.3%; ALT/AST increase and diarrhea 25% each), but without reported objective responses; in late-line mCRC, approved benchmarks like trifluridine/tipiracil + bevacizumab deliver a median PFS ~5.6 months and OS ~10.8 months (and regorafenib OS ~6.4 months), so a “mostly SD” readout without PFS/ORR duration data is hard to position against current SOC.