Seagen Inc. announced data from a phase 1 clinical trial combining SEA-CD40 with chemotherapy and an anti-PD-1 in patients with metastatic PDAC at the ASCO GI annual meeting taking place in San Francisco, January 20 22, 2022. SEA-CD40 is a novel, investigational, nonfucosylated monoclonal receptor-agonistic antibody directed to CD40, which is expressed on antigen-presenting cells. In preclinical models, the combination of SEA-CD40 and chemotherapy resulted in antitumor activity which is further enhanced with anti-PD-1 treatment. In the ongoing phase 1 trial, SEA-CD40 was combined with chemotherapy [gemcitabine and nab-paclitaxel (GnP)], and an anti-PD-1 (pembrolizumab), in 61 patients with untreated metastatic PDAC. Of these, 40 patients received 10 mcg/kg and 21 patients received 30 mcg/kg of SEA-CD40. Key endpoints include confirmed objective response rate (cORR) per RECIST v1.1 by investigator, progression-free survival (PFS) and overall survival (OS). Activity of SEA-CD40 in combination with GnP and pembrolizumab was observed in both doses of SEA-CD40 tested. The overall (N = 61) cORR was 44 percent, median PFS was 7.4 months (95% CI: 5.6-9.0), and median OS was 15.0 months (95 percent CI: 7.8-19.9). Follow-up for efficacy is ongoing. The regimen demonstrated a manageable and tolerable safety profile. Overall, = grade 3 treatment-emergent adverse events (TEAEs) were fatigue, nausea, neutropenia, infusion-related reaction, chills, diarrhea, and pyrexia. This combination also showed evidence of immune activation consistent with the SEA-CD40 mechanism of action.