xaluritamig (AMG 509) / Xencor, Amgen, BeOne Medicines - LARVOL DELTA

Interim results from a phase I study of AMG 509 (xaluritamig), a STEAP1 x CD3 XmAb 2+1 immune therapy, in patients with metastatic castration-resistant prostate cancer (mCRPC) (ESMO 2023) - P1 | "Preliminary PK showed dose-proportional increase in exposure with a mean terminal half-life of approximately 3-4 days. Table: 1765O Lower DLs (DL 1–7) Higher DLs (DL8–15) Overall PSA evaluable N = 43 N = 46 N = 89 PSA ≥ 50%, n (%) 17 (39.5) 25 (54.3) 42 (47.2) PSA ≥ 90%, n (%) 8 (18.6) 16 (34.8) 24 (27.0) RECIST evaluable N = 30 N = 36 N = 66 PR, n (%) 1 (3.3) 14 (38.9) 15 (22.7) SD, n (%) 18 (60.0) 12 (33.3) 30 (45.5) Conclusions Xaluritamig was tolerable with low-grade CRS (occurring primarily cycle 1) with encouraging preliminary efficacy in heavily pretreated pts with mCRPC."

Clinical • Metastases • P1 data • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • STEAP1

Xaluritamig, a STEAP1 × CD3 XmAb 2+1 Immune Therapy for Metastatic Castration-Resistant Prostate Cancer: Results from Dose Exploration in a First-in-Human Study. (PubMed, Cancer Discov) - "Xaluritamig demonstrated encouraging responses (PSA and RECIST) compared with historical established treatments for patients with late-line mCRPC. This study provides proof of concept for T-cell engagers as a potential treatment for prostate cancer, validates STEAP1 as a target, and supports further clinical investigation of xaluritamig in prostate cancer."

Journal • Metastases • P1 data • Fatigue • Genito-urinary Cancer • Musculoskeletal Pain • Oncology • Pain • Prostate Cancer • Solid Tumor • STEAP1

Xaluritamig, a STEAP1 x CD3 XmAb 2+1 immune therapy, in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC): Initial results from dose expansion cohorts in a phase I study (ESMO 2024) - P1 | "This randomized, dose-expansion phase confirmed the safety and efficacy findings from the dose-exploration phase in pts with heavily pretreated mCRPC. A target dose of 1.5 vs 0.75 mg improved the efficacy. Grade 3 AEs were mostly transient, manageable, and allowed treatment continuation in most pts."

Clinical • Metastases • P1 data • Genito-urinary Cancer • Metastatic Castration-Resistant Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor • STEAP1

Evaluation of Xaluritamig in Adults, Adolescents and Children With Relapsed or Refractory Ewing Sarcoma (EWS) (clinicaltrials.gov) - P1 | N=50 | Not yet recruiting | Sponsor: Amgen

New P1 trial • Ewing Sarcoma • Oncology • Pediatrics • Sarcoma • Solid Tumor

Evaluation of Neoadjuvant Xaluritamig in Localized Prostate Cancer (clinicaltrials.gov) - P1 | N=40 | Recruiting | Sponsor: Amgen | Trial primary completion date: Sep 2026 ➔ Jan 2027

Trial primary completion date • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • STEAP1

ADC & cellular therapies may transform prostate cancer. Phase 2s exist but there are 3 RIII trials as @PBarataMD states in this video. I-DXD vs docetaxel is the ADC R3. While 2 bispecifics RII (pasritamig targeting KLK-2 & Xaluritamig targeting STEAP-1) are ongoing @OncoAlert

Clinical

Development of Xaluritamig, a STEAP1-Targeted T-Cell Therapy, for Prostate Cancer (PCF 2025) - No abstract available

Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • STEAP1

STEAP1-targeted strategies in advanced prostate cancer: a review on therapeutic and diagnostic implications. (PubMed, Prostate Cancer Prostatic Dis) - "STEAP1 represents a promising diagnostic and therapeutic target in prostate cancer, and its potential role in shaping future management of the disease warrants continued investigation."

Journal • Review • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • STEAP1

Evaluation of Xaluritamig in High-Risk, Biochemically Recurrent, Non-metastatic Castrate-sensitive Prostate Cancer (clinicaltrials.gov) - P1 | N=50 | Recruiting | Sponsor: Amgen | Trial primary completion date: Dec 2026 ➔ Apr 2027

Trial primary completion date • Genito-urinary Cancer • Hormone Sensitive Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor • STEAP1

STEAP1-targeted strategies in advanced prostate cancer: a review on therapeutic and diagnostic implications (Nature) - "This review discusses STEAP1-based diagnostics, including molecular imaging (89Zr-DFO-MSTP2109A) and liquid biopsy methods, as well as therapeutics, such as STEAP1 antibodies, antibody-drug conjugates (DSPT3086S, ADRX-0405, ABBV-969, and DXC008), chimeric antigen receptor T-cell therapy (STEAP1 CAR-T), bispecific T-cell engagers (Xaluritamig/AMG 509, BC261), and cancer vaccines....STEAP1 represents a promising diagnostic and therapeutic target in prostate cancer, and its potential role in shaping future management of the disease warrants continued investigation."

Review • Prostate Cancer

Unlocking the potential of bispecific T-cell engagers in solid tumors (AACR-NCI-EORTC 2025) - "Clinical advances with tarlatamab (DLL3-targeted TCE, approved for ES-SCLC in 2024) and xaluritamig (STEAP1-targeted TCE, in phase 3 for mCRPC) illustrate that careful antigen choice, combined with innovative engineering, can unlock efficacy even in difficult solid tumor settings. Taken together, the lessons from preclinical and clinical experience emphasize three pillars for successful TCE development in solid tumors: rigorous target biology selection, creative protein engineering to widen the therapeutic index, and thoughtful clinical design to balance safety and efficacy. These principles will guide the next generation of TCEs as they expand across an increasing range of solid tumor indications."

IO biomarker • Castration-Resistant Prostate Cancer • Hematological Malignancies • Lung Cancer • Oncology • Prostate Cancer • Solid Tumor • DLL3 • EPCAM • STEAP1

A Study of Xaluritamig Plus Abiraterone Versus Investigator's Choice in Participants With Chemotherapy-naïve Metastatic Castration-resistant Prostate Cancer (clinicaltrials.gov) - P3 | N=750 | Recruiting | Sponsor: Amgen

New P3 trial • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Study Evaluating the Safety, Tolerability, and Efficacy of Xaluritamig in Combination With Androgen Receptor Pathway Inhibitors in Participants With Metastatic Hormone-sensitive Prostate Cancer (clinicaltrials.gov) - P1 | N=60 | Recruiting | Sponsor: Amgen | Not yet recruiting ➔ Recruiting

Enrollment open • Genito-urinary Cancer • Hormone Sensitive Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor

Study of AMG 509 in Participants With Metastatic Castration-Resistant Prostate Cancer (clinicaltrials.gov) - P1 | N=479 | Recruiting | Sponsor: Amgen | Trial completion date: Aug 2028 ➔ Mar 2032 | Trial primary completion date: Feb 2026 ➔ Mar 2030

Trial completion date • Trial primary completion date • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • CTCs • STEAP1

BeOne Medicines Ltd…announced it has entered into an agreement to sell its royalty rights on the worldwide sales, excluding China, of Amgen’s IMDELLTRA (tarlatamab-dlle) for up to $950 million to Royalty Pharma. (Businesswire) - "Under the terms of the agreement, BeOne will receive an upfront payment of $885 million, with the option to sell remaining royalties within 12 months for up to $65 million. BeOne will share in a portion of the royalty on annual sales above $1.5 billion, and will maintain royalty and all other rights to other assets under the terms of the existing collaboration with Amgen, including xaluritamig, a first-in-class STEAP1 x CD3 XmAb currently being studied in patients with metastatic castration-resistant prostate cancer (mCRPC)."

Commercial • Castration-Resistant Prostate Cancer • Small Cell Lung Cancer

Phase 3 Study of Xaluritamig vs Cabazitaxel or Second Androgen Receptor-Directed Therapy in Participants With Progressive Metastatic Castration-Resistant Prostate Cancer (XALute) (clinicaltrials.gov) - P3 | N=675 | Recruiting | Sponsor: Amgen | Trial completion date: May 2030 ➔ Jul 2029

Trial completion date • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Study Evaluating the Safety, Tolerability, and Efficacy of Xaluritamig in Combination With Androgen Receptor Pathway Inhibitors in Participants With Metastatic Hormone-sensitive Prostate Cancer (clinicaltrials.gov) - P1 | N=60 | Not yet recruiting | Sponsor: Amgen

New P1 trial • Genito-urinary Cancer • Hormone Sensitive Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor

Clinical Pharmacology Characterization and Dose Selection of Xaluritamig, a Next Generation XmAb® 2+1 T-Cell Engager, in Prostate Cancer Patients. (PubMed, J Clin Pharmacol) - "Additionally, thorough dose-exposure-response analyses integrated observed data and model-based simulations of PK, key efficacy endpoints, and safety events to support the evaluation of the target doses 0.75 mg QW, 1.5 mg QW, and 1.5 mg Q2W in dose expansion. This work provides the framework for which modeling and simulations can be used to guide dose selection for dose expansion at an early stage of development adhering to the recent principles of Project Optimus."

Journal • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Hematological Disorders • Hematological Malignancies • Oncology • Prostate Cancer • Solid Tumor • STEAP1

Evaluation of Neoadjuvant Xaluritamig in Localized Prostate Cancer (clinicaltrials.gov) - P1 | N=40 | Recruiting | Sponsor: Amgen | N=30 ➔ 40 | Trial completion date: Oct 2029 ➔ Jan 2030 | Trial primary completion date: Jun 2026 ➔ Sep 2026

Enrollment change • Trial completion date • Trial primary completion date • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • STEAP1

Evaluation of Xaluritamig in High-Risk, Biochemically Recurrent, Non-metastatic Castrate-sensitive Prostate Cancer (clinicaltrials.gov) - P1 | N=50 | Recruiting | Sponsor: Amgen | Trial completion date: Mar 2029 ➔ Jun 2029 | Trial primary completion date: Sep 2026 ➔ Dec 2026

Trial completion date • Trial primary completion date • Genito-urinary Cancer • Hormone Sensitive Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor • STEAP1

T-Cell Engager Therapy in Prostate Cancer: Molecular Insights into a New Frontier in Immunotherapy. (PubMed, Cancers (Basel)) - "While early PSMA-targeted TCEs established proof-of-concept, recent data, notably for six transmembrane epithelial antigen of the prostate 1 (STEAP1)-targeting agents like Xaluritamig, demonstrate more substantial objective responses, highlighting progress through improved target selection and molecular design...Accumulating evidence supports TCEs becoming a new therapeutic pillar for advanced PCa, but achieving this demands sustained innovation focused on optimizing efficacy and safety. This review critically connects molecular engineering advancements with clinical realities and future imperatives."

IO biomarker • Journal • Review • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • DLL3 • STEAP1

Trial in progress (XALute): Phase 3 study of xaluritamig vs investigator's choice of cabazitaxel or second androgen receptor directed therapy (ARDT) in post-taxane metastatic castration-resistant prostate cancer (mCRPC). (ASCO 2025) - P3 | "Exclusion criteria include prior STEAP1-targeted therapy, any anticancer therapy within 4 weeks prior to first dose of study treatment (not including androgen deprivation therapy), prior PSMA-RLT within 2 months of first dose of study treatment unless less than 2 cycles received, and prior radionuclide therapy (radium-223) within 2 months of first dose of study treatment To mitigate risk of cytokine release syndrome, xaluritamig will be administered with step dosing. Cabazitaxel or second ARDT will be administered according to regional prescribing information. Funded by Amgen Inc.; ClinicalTrials.gov number, NCT06691984."

Metastases • P3 data • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Adenocarcinoma • Prostate Cancer • Solid Tumor • STEAP1

ASCO 2025: Trials-in-Progress – XALute: Phase 3 Study of Xaluritamig vs Investigator’s Choice of Cabazitaxel or Second Androgen Receptor-Directed Therapy in Post-Taxane Metastatic Castration-Resistant Prostate Cancer (UroToday) - "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)....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."

Trial status • Castration-Resistant Prostate Cancer

Association of baseline tumor and peripheral biomarker features with efficacy in metastatic castration-resistant prostate cancer patients treated with xaluritamig (AACR 2025) - P3 | "The distribution of somatic tumor mutations was consistent with published mCRPC mutational frequencies, with deleterious alterations in TP53, AR, PTEN and RB1 observed most frequently. Xaluritamig efficacy was observed in patients whose tumors carried these common mCRPC alterations, as well as in patients with detectable TMPRSS2:ERG fusions Taken together, these data suggest that xaluritamig has anti-tumor activity in a broad mCRPC patient population and provide support for enrolling patients with mCRPC in a Phase 3 study of xaluritamig (NCT06691984) regardless of STEAP1 expression levels or tumor mutational status."

Biomarker • Clinical • Metastases • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • CRP • ERG • FOLH1 • PTEN • RB1 • STEAP1 • TMPRSS2 • TP53

A phase 1b, open-label, multicenter study of xaluritamig in patients with biochemical recurrence of prostate cancer after definitive therapy. (ASCO-GU 2025) - P1 | "N Engl J Med. 2024; 391(4):320-333."

Clinical • P1 data • Genito-urinary Cancer • Oncology • Prostate Adenocarcinoma • Prostate Cancer • Solid Tumor • STEAP1