Emavusertib (CA-4948) IRAK4/NF-κB Inhibitor + Gem/Nab-Paclitaxel Posts 20% ORR in 2L PDAC (Phase I)

Emavusertib (CA-4948) is an oral IRAK4 inhibitor designed to blunt pro-survival NF-κB signaling and potentially sensitize PDAC to cytotoxic chemotherapy; it is being dose-escalated with gemcitabine/nab-paclitaxel (G/nP) as second-line therapy in metastatic or unresectable PDAC (Phase I BOIN design; NCI 10522; NCT05685602). In the dose-escalation cohorts, 21 patients were treated (median 3 cycles; range 1–20) and 15 were response-evaluable: ORR was 20% (3/15 PR), DCR 60% (9/15), with no CRs—numerically within/near the published second-line G/nP activity range (ORR ~17% in a prospective phase 2 after FOLFIRINOX; DCR can be substantially higher in select studies), and roughly aligned with retrospective series reporting ORR in the high–single to mid–teens and DCR ~46–58%. Safety was chemo-like and myelosuppressive: grade 3 neutropenia 48% (10/21), grade 3 anemia 19% (4/21), one grade 4 pancytopenia, and DLTs included grade 3 CPK elevation (DL1) and grade 3 diarrhea (DL3); DL4 DLT assessment was ongoing at the time of this report.