Novel Immunotherapy Offers Encouraging Results in First-in-Human Study for Heavily Pretreated mCRPC

Xaluritamig, a novel bispecific XmAb® 2+1 T-cell engager with 2 STEAP1 binding sites designed to facilitate T-cell-mediated lysis of STEAP1-expressing cells, was well tolerated, with low-grade cytokine release syndrome (CRS) and “encouraging” preliminary efficacy in heavily pretreated patients with metastatic castration-resistant prostate cancer (mCRPC), according to the interim results of a phase 1 study presented at the European Society for Medical Oncology Congress 2023.

William Kelly, DO, of Jefferson Health, and colleagues reported results from the first dose exploration of xaluritamig monotherapy in a first-in-human study for patients with mCRPC. Researchers sampled 97 patients who were refractory to prior novel hormone therapy and 1 to 2 taxane regimens, had an Eastern Cooperative Oncology Group performance status of 0-1, and demonstrated adequate organ function.

Xaluritamig was administered intravenously weekly or biweekly with various dose levels (DLs) and schedules (DL1-7, DL8-15). The study objectives were to evaluate safety, tolerability, antitumor activity, and maximum tolerated dose.

As of March 2023, all patients had received at least 1 dose of xaluritamig. Treatment-emergent adverse events (AEs) were reported in 100% of patients (grade ≥3, 74.2%), and 95.9% of patients reported treatment-related AEs (TRAEs; grade ≥3, 52.6%).

The most common AEs were CRS (72.2%), fatigue (52.6%), anemia (45.4%), pyrexia (40.2%), and myalgia (39.2%). CRS was primarily grade 1 or 2. TRAEs leading to discontinuation occurred in 17.5% of patients.

In the DL15 weekly cohort, 3 of 6 evaluable patients experienced dose-limiting toxicities, which led Dr. Kelly and colleagues to define DL14 weekly as the maximum tolerated dose.

Additionally, researchers found that ≥50% prostate-specific antigen (PSA) decline occurred in 42 patients (47.2%), and ≥90% PSA decline occurred in 24 patients (27.0%). PSA responses were more frequent at higher DLs (DL8-15) than in lower DLs (DL1-7).

Furthermore, they noted that Response Evaluation Criteria in Solid Tumors responses included 15 (22.7%) confirmed partial responses and 30 (45.5%) stable diseases. At higher DLs, 14 patients (38.9%) had confirmed partial response and 12 (33.3%) had stable disease.

“Xaluritamig was tolerable with low-grade CRS … with encouraging preliminary efficacy in heavily pretreated patients with mCRPC,” researchers concluded.