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

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

7/ Encouraging prelim findings from #AMG-509(xaluritamig): T cell engager targeting #STEAP1 immunotherapy in patients with #mCRPC improves clinical outcomes. Phase I safe and tolerable. #kelly @LenAppleman @CD_AACR https://aacrjournals.org/cancerdiscovery/article/doi/10.1158/2159-8290.CD-23-0964/729658/

Study of AMG 509 in Participants With Metastatic Castration-Resistant Prostate Cancer (clinicaltrials.gov) - P1 | N=441 | Recruiting | Sponsor: Amgen | Trial completion date: Jun 2028 ➔ Mar 2028 | Trial primary completion date: Jun 2026 ➔ Mar 2026

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

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 Asia 2023) - P1 | "Preliminary PK showed dose-proportional increase in exposure with a mean terminal half-life of approximately 3-4 days. 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 • Metastatic Castration-Resistant Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor • STEAP1

AMG 509 (Xaluritamig) in Patients With mCRPC (PracticeUpdate) - "Dr. Sartor: Also presented at ESMO 2023 is an interesting first-in-human study of a novel compound called AMG 509. Let me explain what this is because you may not be familiar with it. This is a bispecific antibody. One arm of the antibody binds to STEAP1, which is an antigen on the surface of prostate cancer cells. The other arm of the antibody binds to CD3, a T-cell engager, and this bispecific engagement is going to create T-cell activation in the microenvironment of prostate cancer cells expressing the STEAP1 antigen."

Interview • Video

AMGEN REPORTS THIRD QUARTER FINANCIAL RESULTS (PRNewswire) - P1b | N=441 | NCT04221542 | Sponsor: Amgen | "In October, initial data from a Phase 1b study were presented and simultaneously published in Cancer Discovery on xaluritamig, a first-in-class bispecific molecule targeting six-transmembrane epithelial antigen of prostate 1 (STEAP1) demonstrating encouraging anti-tumor activity in heavily pretreated patients with metastatic castrate-resistant prostate cancer (mCRPC). Efficacy was greater at higher doses (doses ≥0.75 mg target dose) where PSA50 was 59% (n=44) and RECIST objective response rate was 41% (n=37). The safety profile was clinically manageable, with CRS that was generally low grade and primarily in cycle 1. A Phase 1b monotherapy and combination dose-escalation and expansion study of xaluritamig in mCRPC continues to enroll patients. Two additional Phase 1 studies of xaluritamig to evaluate preliminary efficacy and safety in patients with early prostate cancer are planned."

P1 data • Trial status • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

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

AMGEN TO WEBCAST INVESTOR CALL AT ESMO 2023 (PRNewswire) - "Amgen...today announced that it will host a webcasted call for the investment community at 8:00 a.m. ET on Tuesday, Oct. 24, 2023 following the presentation of new data from Amgen's innovative oncology portfolio including AMG 193 at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics 2023 and data from tarlatamab, xaluritamig, and LUMAKRAS^® (sotorasib) that will be presented at the European Society for Medical Oncology (ESMO) Congress 2023."

Clinical data • Oncology • Solid Tumor

Xaluritamig: “MTD was established utilizing step-dosing and pre-medication-1.5 mg IV QW (3-step, D1 0.1 mg/D8 0.3 mg/D15 1.0 mg/D22+ 1.5 mg)”; Metastatic castration-resistant prostate cancer (Amgen) - ESMO 2023: “The safety profile was clinically manageable, with CRS that was generally low grade and primarily in cycle 1”

P1 data • Oncology • Prostate Cancer

Impressive safety & efficacy data by Dr. Kelly on T cell engager targeting STEAP1 (xaluritamig)published in @CD_AACR supporting more development @myESMO @OncoAlert @JessicaHawleyMD @neerajaiims @DrChoueiri @TiansterZhang @DrRanaMcKay @urotoday @jklee_lab @HsiehLab @DrScottTagawa

AMG 509 (Xaluritamig), an Anti-STEAP1 XmAb 2+1 T-cell Redirecting Immune Therapy with Avidity-Dependent Activity Against Prostate Cancer. (PubMed, Cancer Discov) - "The avidity-driven activity of AMG 509 enables selectivity for tumor cells with high STEAP1 expression compared with normal cells. AMG 509 is the first STEAP1 TCE to advance to clinical testing, and we report a case study of a mCRPC patient who achieved an objective response on AMG 509 treatment."

Journal • 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

AMGEN TO PRESENT NEW RESEARCH FROM ONCOLOGY PORTFOLIO AND PIPELINE AT ESMO 2023 (PRNewswire) - P1 | N=441 | NCT04221542 | Sponsor: Amgen | "Amgen...announced the presentation of new data across its broad oncology portfolio and pipeline at the European Society for Medical Oncology (ESMO) Congress 2023....Interim results from a Phase 1 study of AMG 509 (xaluritamig) will be presented during a Proffered Paper Oral Session (Abstract #1765O), demonstrating that the novel bispecific STEAP1 x CD3 XmAb^® 2+1 T-cell engager had a positive benefit/risk profile with robust anti-tumor activity in heavily pretreated patients with mCRPC (N=97). Overall, of the 67 RECIST-evaluable patients, 16 (24%) had confirmed partial responses (PR) and 32 (48%) had stable disease (SD), demonstrating encouraging preliminary efficacy. At higher dosing levels (n=37), 15 patients (41%) had confirmed PR and 14 (38%) with SD. The most common treatment-related adverse events were cytokine release syndrome (CRS; 72%; primarily low grade), fatigue (45%), myalgia (34%) and pyrexia (32%)."

P1 data • Prostate Cancer

Xencor Reports Second Quarter 2023 Financial Results (Businesswire) - "Interim results from a Phase 1 study of xaluritamig (AMG 509), a STEAP1 x CD3 XmAb 2+1 bispecific antibody, in patients with mCRPC were accepted for presentation at the European Society for Medical Oncology (ESMO) Congress on October 20, 2023."

P1 data • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

AMGEN REPORTS FIRST QUARTER FINANCIAL RESULTS (PRNewswire) - "Xaluritamig (formerly AMG 509): A Phase 1 dose-escalation/expansion study of xaluritamig, a bispecific molecule targeting six-transmembrane epithelial antigen of prostate 1 (STEAP1) in metastatic castrate-resistant prostate cancer (mCRPC), continues to enroll patients. Initial data readout is anticipated in H2 2023."

P1 data • Trial status • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

[VIRTUAL] AMG 509, a STEAP1 x CD3 bispecific XmAb® 2+1 immune therapy, exhibits avidity-driven binding and preferential killing of high STEAP1-expressing prostate and Ewing sarcoma cancer cells (SITC 2020) - P1 | "Conclusions AMG 509 is a specific, first-in-class T cell-recruiting antibody with avidity-driven activity against STEAP1-positive malignancies. AMG 509 is currently being evaluated for safety, pharmacokinetics, and efficacy in a phase 1, first-in-human study in patients with mCRPC (NCT04221542)."

Ewing Sarcoma • Genito-urinary Cancer • Oncology • Prostate Cancer • Sarcoma • Solid Tumor • CD8 • STEAP1

Study of AMG 509 in Participants With Metastatic Castration-Resistant Prostate Cancer (clinicaltrials.gov) - P1 | N=464 | Recruiting | Sponsor: Amgen | Trial completion date: Nov 2027 ➔ Jun 2028 | Trial primary completion date: Nov 2025 ➔ Jun 2026

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

AMG 509: Preliminary data from P1 trial (NCT04221542) for mCRPC in H2 2023 (Amgen) - Q4 2022 Results

P1 data • Oncology • Prostate Cancer