(UroToday.com) The 2025 American Society of Clinical Oncology (ASCO) Annual Meeting held in Chicago, IL between May 30th and June 3rd, 2025, was host to a prostate, testicular, and penile cancers poster session. Dr. William Kelly presented the ongoing XALute study, a phase III trial of xaluritamig versus investigator’s choice of cabazitaxel or second androgen receptor-directed therapy in post-taxane metastatic castration-resistant prostate cancer (mCRPC).
The median overall survival of mCRPC patients remains <2 years, even with newer therapies available.1 Xaluritamig, an XmAb 2+1 T-cell engager that targets STEAP1, facilitates lysis of STEAP1-expressing cancer cells, such as those in advanced prostate cancer.2,3
In a first-in-human study, xaluritamig demonstrated encouraging efficacy and a manageable safety profile for patients with mCRPC refractory to standard of care therapies.4 Based on the biological mechanism of xaluritamig, key safety risks include cytokine release syndrome (CRS), rash, musculoskeletal inflammation, and immune effector cell-associated neurotoxicity syndrome (ICANS).4
XALute is a randomized, multi-center, open-label, phase III study (NCT06691984) to evaluate the efficacy and safety of xaluritamig versus investigator’s choice of cabazitaxel or second androgen receptor pathway inhibitor (ARPI) in patients with mCRPC previously treated with taxane chemotherapy.
Approximately 675 patients will be randomized in the study. The total study duration is expected to be approximately 56 months from the first patient randomized, with an enrollment duration of approximately 20 months and 36 months treatment and follow-up. Patients will be randomized 2:1 to receive either xaluritamig monotherapy or investigator’s choice of cabazitaxel or second ARPI.
The key inclusion criteria are as follows:
- Adults ≥18 years of age with histological, pathological and/or cytological confirmation of adenocarcinoma of the prostate.
- mCRPC with ≥ 1 metastatic lesion present on baseline CT, MRI, or bone scan imaging obtained within 28 days prior to enrollment.
- Evidence of progressive disease, defined as ≥1 PCWG3 criteria.
- Prior orchiectomy and/or ongoing androgen-deprivation therapy and a castrate level of serum testosterone.
- Prior treatment with at least one ARPI.
- Prior treatment with one taxane therapy in the mCRPC setting.
- ECOG PS of 0 or 1.
The key exclusion criteria are as follows:
- Prior STEAP1-targeted therapy.
- Any anticancer therapy, immunotherapy, or investigational agent within 4 weeks prior to first dose of study treatment, not including androgen suppression therapy.
- Prior PSMA radioligand or radionuclide therapy within 3 months of first dose of study treatment.
The primary study endpoint is overall survival, with key secondary endpoints as follows:
- Radiographic progression-free survival per PCWG3-modified RECIST v1.1, as assessed by blinded independent central review (BICR)
- Objective response and duration of response per RECIST v1.1, as assessed by BICR
- Disease control
- Time to response per RECIST v1.1, as assessed by BICR
- Time to first symptomatic skeletal event
- Adverse events and fatal adverse events
- Health-related quality of life
Presented by: William Kevin Kelly, DO, Chair, Professor, Department of Medical Oncology, Thomas Jefferson University Hospital, Philadelphia, PA
Written by: Rashid K. Sayyid, MD, MSc – Robotic Urologic Oncology Fellow at The University of Southern California, @rksayyid on Twitter during the American Society of Clinical Oncology (ASCO) 2025 Annual Meeting, Chicago, IL, Fri, May 30 – Tues, Jun 3, 2025.
Related content: Xaluritamig vs. Standard Care: A Phase 3 Trial for ARPI/Taxane-Refractory mCRPC - William Kevin Kelly
- Freedland SJ, Yu EY, Shore ND, et al. Emerging therapies in prostate cancer management. Prostate Cancer Prostatic Dis. 2024;27:327.
- Gomes IM, Arinto P, Lopes C, et al. Estrogen receptor signaling in prostate cancer: mechanisms and clinical implications. Prostate. 2013;73:605.
- Nolan-Stevaux O, Liu W, Tang J, et al. Targeting adaptive immune resistance in prostate cancer. Cancer Discov. 2024;14:90.
- Kelly WK, Trudel GC, Antonarakis ES, et al. Advances in biomarker-driven strategies for prostate cancer. Cancer Discov. 2024;14:76.