ESMO 2024: Xaluritamig (AMG 509), a STEAP1 x CD3 XmAb 2+1 immune therapy for Metastatic CRPC: initial results of Phase 1

[Maxone73]

Xaluritamig, a novel bispecific T-cell engager targeting STEAP1, in patients with metastatic castration-resistant prostate cancer (mCRPC).

STEAP1 is a cell surface antigen highly expressed in prostate cancer and is associated with poor prognosis. Xaluritamig is designed to redirect T-cells to kill STEAP1-expressing cancer cells, offering a targeted immunotherapeutic approach.

The study enrolled 106 patients with mCRPC who were refractory to prior hormonal therapies and had received one or two taxane regimens. Participants were randomized to receive xaluritamig at different dosing schedules: 0.75 mg weekly, 1.5 mg weekly, or 1.5 mg every two weeks. The primary objectives were to evaluate the efficacy and safety of these dosing regimens.

Results showed that the 1.5 mg every two weeks dosing schedule provided the most favorable balance of efficacy and safety. Nearly half of the patients (49.5%) experienced a significant reduction in prostate-specific antigen (PSA) levels of 50% or more, indicating a meaningful antitumor response. Higher dose levels (1.5 mg) were associated with more frequent PSA responses compared to the lower dose. Additionally, 20% of patients achieved an objective tumor response, including one complete response, and almost half achieved stable disease.

The trial also demonstrated that STEAP1 is an effective target for prostate cancer therapies.

The treatment was generally well-tolerated. The most common treatment-related adverse event was cytokine release syndrome (CRS), occurring in about 75% of patients, mostly during the first treatment cycle and generally manageable. Musculoskeletal events were also observed but were less frequent in the every two weeks dosing group. Serious adverse events led to treatment discontinuation in 16% of patients, but no fatal treatment-related events were reported.

The 1.5 mg every two weeks regimen emerged as the recommended dose for future phase 3 trials due to its optimal efficacy and tolerability.

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