Xencor (XNCR) Study Result summary

Study design and patient population

• Phase 1, multicenter, open-label, dose-escalation and expansion study of XmAb819 in advanced clear cell renal cell carcinoma (ccRCC), with both IV and SC cohorts; data cut-off September 19, 2025.

• 69 heavily pretreated patients enrolled, all with prior anti-PD1 and VEGF-TKI therapy; median of 4 prior systemic therapies, 36% had HIF2a inhibitor exposure.

• Study objectives include safety, tolerability, pharmacokinetics, and anti-tumor activity, using a 3+3+3 dose-escalation design.

• No preselection for ENPP3 expression; retrospective testing ongoing.

• XmAb819 targets ENPP3 using XmAb 2+1 bispecific antibody technology.

Safety and tolerability

• XmAb819 was generally well tolerated, with only 4% discontinuing due to adverse events; most AEs were low grade, including CRS, rash, and GI toxicities.

• Grade 3 CRS occurred in 4% of patients with correct dose prep; higher rates (up to 28%) seen with preparation errors, which were mitigated by site retraining and a new formulation.

• No cases of ICANS or Grade 5 events reported; most AEs occurred during priming and resolved quickly.

• Grade 3 treatment-related events included rash (16%) and liver enzyme elevations (7%); one dose-limiting Grade 4 liver enzyme elevation.

• Maculopapular rash was transient and manageable with supportive care.

Pharmacokinetics

• XmAb819 demonstrated an IV half-life of 8–9 days and SC Tmax of 5.5 days, with 55–70% absolute bioavailability for SC dosing.

• Steady-state drug concentrations in higher dose cohorts fell within the target range expected for anti-tumor activity.