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

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

A phase 1b, open-label, multicenter study of xaluritamig in patients with newly diagnosed localized intermediate- or high-risk prostate cancer in the neoadjuvant setting. (ASCO-GU 2025) - P1 | "Secondary outcomes will assess PSA response, imaging-based response on multiparametric magnetic resonance imaging (mpMRI) prior to prostatectomy, pathologic response and the pharmacokinetics of xaluritamig. The study is open for enrollment as of October 2024."

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

Phase 3 Study of Xaluritamig vs Cabazitaxel or Second Androgen Receptor-Directed Therapy in Participants With Progressive Metastatic Castration-Resistant Prostate Cancer (clinicaltrials.gov) - P3 | N=675 | Recruiting | Sponsor: Amgen | Not yet recruiting ➔ Recruiting | Trial completion date: Nov 2029 ➔ May 2030 | Trial primary completion date: Aug 2028 ➔ Dec 2028

Enrollment open • Metastases • Trial completion date • Trial primary completion date • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Evaluation of Neoadjuvant Xaluritamig in Localized Prostate Cancer (clinicaltrials.gov) - P1 | N=30 | Recruiting | Sponsor: Amgen | Not yet recruiting ➔ Recruiting

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

Phase 3 Study of Xaluritamig vs Cabazitaxel or Second Androgen Receptor-Directed Therapy in Participants With Progressive Metastatic Castration-Resistant Prostate Cancer (clinicaltrials.gov) - P3 | N=675 | Not yet recruiting | Sponsor: Amgen

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

#UromigosLive24 T Cell Directed Therapy Panel Part 2: Existing Data for T Cell Engagers in CRPC (YouTube) - "At Uromigos Live 2024, a panel moderated by Brian Rini focused on T cell directed therapy in prostate cancer and featured discussion on topics including cytokine release syndrome and new trials analyzing acapatamab, xaluritamig, and tarlatamab."

Video • Renal Cell Carcinoma

Xencor Reports Third Quarter 2024 Financial Results (Businesswire) - P1 | N=461 | NCT04221542 | Sponsor: Amgen | "Results from a Phase 1 study evaluating xaluritamig...in patients with mCRPC were presented at the European Society for Medical Oncology (ESMO) Congress in September 2024. With a median follow-up time of 27.9 months, the median overall survival (OS) was 17.7 months across all cohorts. A PSA90 rate of 45.1% was also observed in high-dose cohorts, and PSA90 response was associated with survival (p = 0.0044), which Amgen believes could potentially serve as an early indicator for benefit in these patients. Amgen has indicated that a Phase 3 study in patients with post-taxane mCRPC will be initiated in the fourth quarter of 2024."

New P3 trial • P1 data • Castration-Resistant Prostate Cancer

#UromigosLive24 T Cell Directed Therapy Panel Part 1: T Cell Engagers and Cytokine Release Syndrome (YouTube) - "In part one of the session, the panelists discuss T cell engagers, including an introduction and discussion of cytokine release syndrome."

Video

Evaluating CTC enumeration & PSA measurements in prostate cancer (YouTube) - "Andrew Armstrong, MD...discusses the future of xaluritamig, which was assessed in a dose exploration trial (NCT04221542). Circulating tumor cell (CTC) enumeration, which is FDA-approved, was shown to potentially complement PSA measurements. While most patients showed declines in both PSA and CTCs, some exhibited CTC reduction without corresponding PSA decline, suggesting that CTC monitoring may provide additional insights for therapeutic decision-making and drug development. This interview took place at the European Society for Medical Oncology (ESMO) 2024 Congress in Barcelona, Spain."

Interview • Video

Xaluritamig (AMG 509) and its role in targeting prostate cancer (YouTube) - "Andrew Armstrong, MD...gives an overview of xaluritamig (AMG 509), a bispecific T-cell engager targeting STEAP1, an androgen receptor (AR)-regulated cell surface protein highly expressed in advanced prostate cancer. Xaluritamig enhances immune response by directing T-cells to the tumor microenvironment, facilitating the destruction of prostate cancer cells. This interview took place at the European Society for Medical Oncology (ESMO) 2024 Congress in Barcelona, Spain."

Interview • Video

Evaluation of Xaluritamig in High-Risk, Biochemically Recurrent, Non-metastatic Castrate-sensitive Prostate Cancer (clinicaltrials.gov) - P1 | N=40 | Recruiting | Sponsor: Amgen | Not yet recruiting ➔ Recruiting

Enrollment open • Metastases • Castration-Sensitive Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • STEAP1

Evaluation of Neoadjuvant Xaluritamig in Localized Prostate Cancer (clinicaltrials.gov) - P1 | N=30 | Not yet recruiting | Sponsor: Amgen

New P1 trial • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • STEAP1

Circulating tumour cell (CTC) enumeration and overall survival (OS) in men with metastatic castration-resistant prostate cancer (mCRPC) treated with xaluritamig (ESMO 2024) - P1 | "Xaluritamig showed prolonged OS relative to historic benchmarks in heavily pretreated pts with poor prognostic features. CTC enumeration is highly prognostic of OS at baseline, and CTC conversion and PSA declines may predict response from xaluritamig treatment. Further validation is warranted as CTCs may guide future clinical development of xaluritamig by early identifying the treatment benefit in pts."

Circulating tumor cells • Clinical • Metastases • Tumor cell • Genito-urinary Cancer • Metastatic Castration-Resistant Prostate Cancer • Oncology • 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

Presented today @myESMO the long term results and CTC correlative studies of Xaluritamig (AMG-509) a STEAP1 T cell engager in men with mCRPC. Very active at higher doses with clear durable PSA, CTC, and imaging responses. @AmgenOncology @DukeGUCancer @DukeCancer

AMGEN TO PRESENT DATA FROM MULTIPLE EARLY-STAGE CLINICAL TRIALS AT ESMO 2024 (PRNewswire) - "Amgen...announced the presentation of new data across its broad oncology pipeline and portfolio at the European Society for Medical Oncology (ESMO) Congress 2024, taking place Sept. 13-17 in Barcelona...Key presentations include: First findings from the Phase 1b study of LUMAKRAS plus Vectibix in combination with FOLFIRI in first-line patients with KRAS G12C-mutated metastatic colorectal cancer (mCRC); Phase 1 dose escalation and initial dose expansion data from AMG 193 selected for a presidential symposium session; First-in-human study of xaluritamig in men with metastatic castration-resistant prostate cancer (mCRPC)."

Clinical data • Castration-Resistant Prostate Cancer • Colorectal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Genito-urinary Cancer • Lung Cancer • Metastatic Castration-Resistant Prostate Cancer • Non Small Cell Lung Cancer • Oncology • Prostate Cancer • Solid Tumor

Evaluation of Xaluritamig in High-Risk, Biochemically Recurrent, Non-metastatic Castrate-sensitive Prostate Cancer (clinicaltrials.gov) - P1 | N=40 | Not yet recruiting | Sponsor: Amgen

Metastases • New P1 trial • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • STEAP1

AMGEN REPORTS SECOND QUARTER 2024 FINANCIAL RESULTS (PRNewswire) - "Second Quarter Product and Pipeline Update:...(i) Xaluritamig (AMG 509):...Updated results from the xaluritamig first-in-human trial, including longer follow-up and overall survival on the previously presented dose-escalation and initial results from dose optimization, will be presented at the European Society for Medical Oncology (ESMO) Congress 2024 in September; (ii) AMG 193:...In August, the FDA granted an orphan drug designation to AMG 193 for the treatment of pancreatic cancer....Additional data from the Phase 1 dose escalation and initial dose expansion study of AMG 193 in patients with MTAP-null solid tumors will be presented at ESMO in September."

Orphan drug • P1 data • Metastatic Castration-Resistant Prostate Cancer • Pancreatic Cancer

Unveiling diverse trimeric forms of STEAP1 in human prostate cancer cells: Exploring STEAP1-STEAP2 interdependence for expression and plasma membrane localization (AACR 2024) - "We recently reported the preclinical characterization of xaluritamig (AMG 509), a STEAP1 XmAb® 2+1 T-cell engager molecule that is being developed for the treatment of prostate cancer (Nolan-Stevaux et al, 2023)...Characterizing the capability of existing STEAP1 or STEAP2 targeting therapeutics to bind their respective targets, whether within a homotrimer or heterotrimer, is crucial for a comprehensive understanding of the therapeutic potential of these drugs. Further research will help delineate the mechanism underlying the formation of STEAP1/2 trimers in cancer cells and continue advancing our understanding of this intriguing biological relationship."

Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • STEAP1 • STEAP2

Study of AMG 509 in Participants With Metastatic Castration-Resistant Prostate Cancer (clinicaltrials.gov) - P1 | N=441 | Recruiting | Sponsor: Amgen | Trial completion date: Mar 2028 ➔ Jul 2028

Metastases • Trial completion date • Genito-urinary Cancer • Metastatic Castration-Resistant Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor • STEAP1