Initial results of a phase 1 dose exploration and expansion study of xaluritamig plus abiraterone acetate (AA) in patients (pts) with mCRPC.

Abstract

5070 Background: Xaluritamig (xalu) is a STEAP1 x CD3 T-cell engager, that has shown potent, durable monotherapy activity in pts with mCRPC progressing on taxane chemotherapy. This activity may be further enhanced when given in combination with an androgen receptor pathway inhibitor (ARPI) prior to chemotherapy or radioligand therapy. We therefore evaluated xalu + AA in chemotherapy-naïve pts with mCRPC as a potential chemo-sparing strategy. Here, we report initial safety and efficacy findings. Methods: This open-label, multicenter phase (ph) 1 dose exploration and expansion study (NCT04221542) enrolled pts who were taxane-naïve in mCRPC and had received ≤ 2 prior ARPIs (no prior AA permitted). In dose exploration, xalu was administered at a target dose of 0.3, 0.75 or 1.5 mg weekly (QW) via 1-, 2- or 3-step up regimen with 1000 mg AA and predniso(lo)ne daily. Expansion cohort was 3-step up dosing to target dose of 1.5 mg QW then 1.5 mg Q2W. Primary endpoints were safety and tolerability; secondary endpoints were pharmacokinetics and antitumor activity. Results: As of data cutoff (15 Oct 2025), 39 pts were enrolled with a median age of 68 years (range: 43–81). Patients received a median of 2 prior therapies, including 56% with prior taxane for mHSPC. Most common treatment-emergent adverse events (all grade [G]/ ≥G3) were myalgia (92.3%/41%), cytokine release syndrome (CRS; 64.1%/7.7%), and anemia (46.2%/12.8%); there were 2 G4 (decrease in lymphocyte count and blood calcium) and no G5 treatment-related AEs reported. Dose-limiting toxicities (n=4) were reported across all dose levels (soft tissue swelling and CRS, 0.3 mg; myalgia n=2, 0.75 and 1.5 mg). Escalation completed at the planned 1.5 mg QW target dose and 1.5 mg Q2W was selected for dose expansion to align with RP3D monotherapy regimen. In the expansion cohort (n=20), confirmed PSA50, PSA90, and objective response rates (RECIST v1.1) were 58%, 47%, and 43%, respectively (Table). Median PSA response duration and radiographic progression free survival were 6.7 (95% CI: 3.8–not estimable [NE]) and 10.5 (95% CI: 8.1–NE) months, respectively. Median OS was not yet reached with 12 months median follow up (95% CI: 11.8–12.3). Seven pts across escalation and expansion remained on treatment. Conclusions: Xalu + AA demonstrated manageable safety and promising antitumor activity in taxane- naive mCRPC and is now being evaluated in the randomized ph3 XALience study (NCT07213674). Clinical trial information: NCT04221542 . Dose Escalation0.3─0.75 mg QWN=11 Dose Escalation1.5 mg QWN=8 Dose Expansion1.5 mg Q2WN=20 TotalN=39 PSA evaluable 11 7 19 37 PSA50 response, n (%) 6 (54.5) 7 (100) 11 (57.9) 24 (64.9) PSA90 response, n (%) 5 (45.5) 7 (100) 9 (47.4) 21 (56.8) Best Overall Response RECIST evaluable 6 1 7 14 Complete response, n (%) 1 (16.7) 0 0 1 (7.1) Partial response, n (%) 3 (50) 1 (100) 3 (42.9) 7 (50) Stable disease, n (%) 1 (16.7) 0 4 (57.1) 5 (35.7) Not evaluable, n (%) 1 (16.7) 0 0 1 (7.1)