Investigational Drug
Xaluritamig
HealthScout AI Analysis
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Overview
Xaluritamig (AMG 509) is an investigational, first‑in‑class bispecific T‑cell–engaging antibody being developed by Amgen for prostate cancer, primarily metastatic castration‑resistant prostate cancer (mCRPC). A Phase 1 first‑in‑human study has reported antitumor activity and defined dose‑limiting toxicities; a global Phase 3 trial in post‑taxane mCRPC is recruiting. (pubmed.ncbi.nlm.nih.gov)
Mechanism of action
Xaluritamig is a STEAP1×CD3 “XmAb 2+1” T‑cell engager with two STEAP1‑binding domains and one CD3‑binding domain. It redirects T cells to lyse STEAP1‑expressing tumor cells and was engineered for avidity‑dependent activity, favoring tumor cells with high STEAP1 expression over normal tissues. Preclinical data showed potent T cell–dependent cytotoxicity and tumor regressions in prostate cancer models. (aacrjournals.org)
Efficacy
Phase 1 (dose exploration; monotherapy, mostly taxane‑pretreated mCRPC): - N=97 treated across weekly or Q2W dosing; median age 67. Confirmed PSA50 responses in 49% overall; at target doses ≥0.75 mg, PSA50 59% and objective response rate (ORR) 41% in RECIST‑evaluable disease. Overall ORR 24%. (pubmed.ncbi.nlm.nih.gov) - ESMO 2023 interim presentation (same study) reported, among 67 RECIST‑evaluable patients, 24% confirmed partial responses and 48% stable disease; at higher dose levels (n=37), 41% PR and 38% SD. PSA50 achieved by 47% overall and 54% at higher doses; PSA90 by 27% overall. (oncologypro.esmo.org)
A randomized Phase 3 study (XALute; NCT06691984) is comparing xaluritamig against cabazitaxel or a second androgen receptor–directed therapy (enzalutamide or abiraterone) with overall survival as the primary endpoint; the trial opened in December 2024 and is recruiting. (cdek.pharmacy.purdue.edu)
Safety
In the Phase 1 dose‑exploration study (N=97): - Most common treatment‑related adverse events: cytokine release syndrome (CRS) 72%, fatigue 45%, myalgia 34%; CRS was predominantly grade 1–2, occurred mainly in cycle 1, and was mitigated with premedication and step‑dosing. Maximum tolerated dose identified as 1.5 mg IV weekly using a 3‑step dose. (pubmed.ncbi.nlm.nih.gov) - ESMO 2023 interim reported grade ≥3 CRS in about 2% (1 event grade 3); other frequent events included pyrexia and anemia. Treatment‑related adverse events leading to discontinuation occurred in 17.5% of patients in the presented dataset. (oncologypro.esmo.org)
Preliminary pharmacokinetics showed dose‑proportional exposure with a terminal half‑life of approximately 3–4 days. (oncologypro.esmo.org)
Ongoing and planned studies
- Phase 1 monotherapy and combination cohorts with enzalutamide or abiraterone continue to enroll; outpatient dosing cohorts are being explored. A neoadjuvant Phase 1b study in localized intermediate/high‑risk prostate cancer initiated in November 2024. (amgen.com)
Further reading
- Cancer Discovery (first‑in‑human dose‑exploration study; peer‑reviewed). (pubmed.ncbi.nlm.nih.gov)
- Cancer Discovery (mechanistic/preclinical study of xaluritamig). (pubmed.ncbi.nlm.nih.gov)
- ESMO 2023 abstract/interim clinical results. (oncologypro.esmo.org)
- Phase 3 XALute trial listing (study design and status). (cdek.pharmacy.purdue.edu)
- Amgen updates on program status (development pipeline context). (investors.amgen.com)
Last updated: Oct 2025
Active trials using Xaluritamig
Found 4 active trials using this drug:
HealthScout AI summary: Chemotherapy-naïve mCRPC adults (ECOG 0–1) who progressed on exactly one prior AR pathway inhibitor (enzalutamide, apalutamide, or darolutamide) and remain on castration are randomized to xaluritamig plus abiraterone versus investigator’s choice of abiraterone, docetaxel, or cabazitaxel. Xaluritamig (AMG 509) is a STEAP1×CD3 bispecific T‑cell engager designed to redirect T‑cell cytotoxicity; exclusions include prior abiraterone progression, prior STEAP1 therapy, mCRPC chemo, significant prior radionuclide/PSMA therapy, and neuroendocrine histology.
ClinicalTrials.gov ID: NCT07213674
HealthScout AI summary: Adults with de novo, high-volume metastatic hormone-sensitive prostate adenocarcinoma on ADT (with or without recent darolutamide or abiraterone) and no prior docetaxel are treated with xaluritamig plus either darolutamide or abiraterone. Xaluritamig (AMG 509) is an investigational STEAP1×CD3 bispecific T‑cell engager; the study assesses safety and preliminary activity of these combinations.
ClinicalTrials.gov ID: NCT07140900
HealthScout AI summary: Adults with mCRPC who have progressed on at least one AR-directed therapy and received exactly one prior taxane in the mCRPC setting (ECOG 0–1) are randomized to xaluritamig, a STEAP1×CD3 bispecific T‑cell engager, versus investigator’s choice of cabazitaxel or a second AR-directed therapy (abiraterone or enzalutamide). Suitable for patients with measurable or bone disease and no prior STEAP1‑targeted therapy; primary endpoint is overall survival.
ClinicalTrials.gov ID: NCT06691984
HealthScout AI summary: Adults with metastatic castration-resistant prostate cancer on continuous androgen suppression, including post–novel hormonal therapy and often post-taxane, receive xaluritamig (AMG 509), a STEAP1×CD3 bispecific T‑cell engager, as IV or SC monotherapy or in combination with abiraterone or enzalutamide. Excludes small cell/neuroendocrine histology and untreated CNS disease; aims to define dosing while assessing early antitumor activity.
ClinicalTrials.gov ID: NCT04221542
