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

Outpatient administration of xaluritamig for metastatic castration-resistant prostate cancer (mCRPC): feasibility and safety from a first-in-human study (ESMO 2026) - No abstract available

Clinical • First-in-human • Metastases • P1 data • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Trial of Xaluritamig in Adults With Metastatic Castration-resistant Prostate Cancer (clinicaltrials.gov) - P1 | N=40 | Recruiting | Sponsor: Amgen | Trial primary completion date: Jan 2028 ➔ Jul 2030

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

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 High-Risk, Biochemically Recurrent, Non-metastatic Castrate-sensitive Prostate Cancer (clinicaltrials.gov) - P1 | N=50 | Active, not recruiting | Sponsor: Amgen | Trial completion date: Dec 2028 ➔ May 2029 | Trial primary completion date: Oct 2026 ➔ Mar 2027

Trial completion date • Trial primary completion date • Genito-urinary Cancer • Hormone Sensitive Prostate Cancer • Oncology • Prostate Adenocarcinoma • 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 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

Initial results of a phase 1 dose exploration and expansion study of xaluritamig plus abiraterone acetate (AA) in patients (pts) with mCRPC. (ASCO 2026) - P1, P3 | "Xalu + AA demonstrated manageable safety and promising antitumor activity in taxane- naive mCRPC and is now being evaluated in the randomized ph3 XALience study (NCT07213674)."

Clinical • P1 data • Castration-Resistant Prostate Cancer • Hematological Disorders • Musculoskeletal Pain • Prostate Cancer • STEAP1

Immunohistochemical Evaluation of STEAP1 Expression in Thoracic Malignancies (IASLC-TTLC 2026) - "A Phase 3 trial with STEAP1-targeted T-cell engager, Xaluritamig, is currently ongoing in prostate cancer... STEAP1 is consistently expressed in NSCLC with significantly higher expression in tumors harboring driver mutations, especially in MET exon 14, ALK, and RET alterations. Uniformly strong STEAP1 expression was observed in thymic carcinoma, while expression was modest to high in SCLC. Expansion of these cohorts is planned to validate these findings and inform development of STEAP1-targeted therapies in thoracic malignancies."

Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • Thoracic Cancer • ALK • EGFR • MET • ROS1 • STEAP1

LuX: Xaluritamig in Participants With Metastatic Castrate Resistant Prostate Cancer and Suboptimal Response to Lutetium 177 Vipivotide Tetraxetan (clinicaltrials.gov) - P2 | N=30 | Not yet recruiting | Sponsor: Thomas Jefferson University | Initiation date: Jul 2026 ➔ Oct 2026

Trial initiation date • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • STEAP1

LuX: Xaluritamig in Participants With Metastatic Castrate Resistant Prostate Cancer and Suboptimal Response to Lutetium 177 Vipivotide Tetraxetan (clinicaltrials.gov) - P2 | N=30 | Not yet recruiting | Sponsor: Thomas Jefferson University

New P2 trial • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • STEAP1

Immunotherapeutic strategies for castration-resistant prostate cancer: A systematic review of mechanisms, clinical advances and emerging approaches. (PubMed, Mol Biol Rep) - "These findings demonstrate the significant potential of immunotherapy in treating CRPC, but treatment regimens require further optimization and validation of long-term survival benefits through Phase III clinical trials."

IO biomarker • Journal • Review • Tumor mutational burden • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • MUC1 • PSCA • TMB

Orbital Inflammatory Syndrome Associated with Bispecific T-Cell Engager Therapy: Case and Literature Review. (PubMed, Ophthalmic Plast Reconstr Surg) - "Two days after xaluritamig administration, a 70-year-old man developed right-sided periorbital swelling with significantly reduced vision, proptosis, and restricted extraocular motility...Symptoms resolved with intravenous methylprednisolone followed by an oral taper...BiTE therapies may elicit off-target orbital inflammation via immune activation pathways similar to those described with immune checkpoint inhibitors, despite their distinct mechanisms of T-cell engagement. This case underscores the need for vigilant ocular monitoring and judicious steroid management during BiTE therapy."

Journal • Inflammation • Ocular Inflammation • Oncology

A phase 1b study of xaluritamig (a STEAP1 x CD3 T-cell engager) in pediatric, adolescent, and adult patients with relapsed/refractory (R/R) Ewing sarcoma. (ASCO 2026) - P1 | "Cancer Discov. 2024; 14(1):76-89."

Clinical • P1 data • Castration-Resistant Prostate Cancer • Ewing Sarcoma • Genito-urinary Cancer • Osteosarcoma • Pediatrics • Prostate Cancer • Sarcoma • Solid Tumor • CD8 • EWSR1 • FLI1 • IL6 • STEAP1

XALience: A phase 3, open-label, multicenter, randomized study of xaluritamig plus abiraterone vs investigator's choice in patients with chemotherapy-naïve metastatic castration-resistant prostate cancer. (ASCO 2026) - P3 | "Approximately 750 eligible patients ≥18 years old with histologically confirmed chemotherapy-naïve mCRPC; evidence of disease progression on prior enzalutamide, apalutamide, or darolutamide; ECOG PS of 0-1; and adequate organ function and who may have previously received ≤6 cycles of docetaxel in the metastatic hormone-sensitive prostate cancer (mHSPC) setting will be randomized 1:1 to receive xaluritamig plus abiraterone or investigator's choice of docetaxel, cabazitaxel, or abiraterone. 2024; 35: S963-S964. Data on file, Amgen; 2025."

Clinical • First-in-human • Metastases • P3 data • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Hormone Sensitive Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor • STEAP1

Trial of Xaluritamig in Adults With Metastatic Castration-resistant Prostate Cancer (clinicaltrials.gov) - P1 | N=40 | Recruiting | Sponsor: Amgen | Not yet recruiting ➔ Recruiting | Trial completion date: Nov 2029 ➔ Jul 2030 | Trial primary completion date: May 2027 ➔ Jan 2028

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

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=707 | Active, not recruiting | Sponsor: Amgen | Recruiting ➔ Active, not recruiting

Enrollment closed • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Adenocarcinoma • Prostate Cancer • Solid Tumor

An integrated preclinical platform for comprehensive evaluation of T-Cell engagers (AACR 2026) - "AMG509 (targeting STEAP1), AMG757 (targeting DLL3), and IBI-389 (targeting CLDN18.2) were evaluated in models of prostate cancer, small-cell lung cancer, and patient-derived xenografts (PDX), respectively. In the BALB/c-hCD3EDG syngeneic model, administration of the CD3/CD20 bispecific antibody led to 81.5% tumor growth inhibition after 18 days.GemPharmatech's integrated strategy—combining in vitro screening with a range of in vivo models such as NCG, NCG-MHC-dKO, and CD3-humanized mice—enables rapid, scalable, and translationally relevant assessment of T-cell engager candidates. This comprehensive platform supports robust and efficient immuno-oncology drug discovery and development."

IO biomarker • Preclinical • Gastric Cancer • Genito-urinary Cancer • Hematological Malignancies • Lung Cancer • Lymphoma • Oncology • Pancreatic Cancer • Prostate Cancer • Small Cell Lung Cancer • Solid Tumor • CD3D • CD3E • CD3G • CLDN18 • DLL3 • STEAP1

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 | Active, not recruiting ➔ Recruiting

Enrollment open • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Adenocarcinoma • Prostate Cancer • Solid Tumor

SCR-M030, an innovative and potential first-in-class trispecific T cell engager targeting PSMA and STEAP1 for mCRPC (AACR 2026) - "Notably, in the 22RV1 model, SCR-M030 exhibited more potent tumor suppression than the AMG509 analog. In conclusion, the novel trispecific TCE SCR-M030 is a strategically designed therapy that demonstrates potent efficacy against challenging low-expression tumors by simultaneously targeting PSMA and STEAP1 with differential affinity. Its robust in vivo performance, favorable pharmacokinetics, and superiority over a relevant comparator underscore its strong potential as a next-generation therapeutic for prostate cancer."

Trispecific • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • STEAP1

QLS2401: A novel PSMA/STEAP1/CD3 tri-specific T-cell engager for the treatment of mCRPC (AACR 2026) - "QLS2401 was well-tolerated in a toxicity study in cynomolgus monkeys, with an HNSTD (Highest Non-Severely Toxic Dose) significantly higher than that of the xaluritamig analog. In conclusion, preclinical studies have demonstrated that QLS2401 exhibits an expanded therapeutic window, superior efficacy and improved tolerability compared to the xaluritamig analog."

Trispecific • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • STEAP1

A biparatopic DLL3-targeting trispecific T-cell engager delivered by mRNA-LNP drives potent anti-tumor activity in vitroandin vivo (AACR 2026) - "Against SHP-77 cells, MTS108 exhibited an EC₅₀ more than 10-fold lower than that of the approved therapeutic Xaluritamig. These data demonstrate that an mRNA-LNP platform can effectively deliver a biparatopic DLL3-targeting trispecific TCE with potent and superior anti-tumor activity and a favorable safety profile. MTS108 represents a promising therapeutic candidate and supports advancement of mRNA-encoded TCEs toward clinical evaluation."

Preclinical • Trispecific • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • DLL3

A novel anti-CD3×CD28×STEAP1 tri-specific T-cell engager with enhanced and durable antitumor responses in prostate cancer (AACR 2026) - "HLX3902 demonstrated enhanced T cell function and sustained in vitro cytotoxicity compared with bispecific TCEs and their combinations, showing superior T-cell proliferation and enhanced expansion of memory T cells. Furthermore, Anti-CD3×CD28×STEAP1 TCE demonstrated superior and sustained antitumor activity in both humanized PBMC/cell line-derived xenograft and PDX models at a single 0.01 mg/kg dose, with increased T-cell infiltration, activation, and persistent intratumoral CD8+ T cells resulting from CD28 co-stimulation compared to AMG509... We developed a novel tri-specific TCE with optimized CD3 and CD28 signaling, effectively co-engages T cells and STEAP1-expressing tumor cells. It elicits potent, target-dependent T-cell activation and cytotoxicity, The incorporation of CD28 signaling significantly improved T-cell persistence and sustained functional activity against repeated antigen challenges in vitro and in vivo. It was well tolerated in cynomolgus..."

Trispecific • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • CD8 • STEAP1

One-stop solution for preclinical evaluation of bispecific T-cell engagers targeting STEAP1 (AACR 2026) - "AMG509 (Xaluritamig), a Phase III STEAP1×CD3 TCE currently in clinical development, was used as a benchmark molecule to validate platform performance...By integrating antigen quantification, immune functional assays, and humanized in vivo systems, GemPharmatech's platform enables comprehensive and reproducible assessment of emerging TCE modalities. This work provides valuable preclinical insight into STEAP1 biology and establishes an experimental foundation for future therapeutic programs targeting this clinically relevant antigen."

Bispecific • IO biomarker • Preclinical • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • CD69 • IFNG • IL2 • IL2RA • IL6 • STEAP1 • TNFA

XmAb808, a B7H3-targeted CD28 bispecific antibody, costimulates T cells enhancing the anti-tumor activity of clinically active CD3 T cell engagers (AACR 2026) - "Notably, XmAb808 synergistically enhanced the activity of XmAb541 (CLDN6xCD3) and an analog of xaluritamig (STEAP1xCD3), two programs with clinically observed anti-tumor activity. Moreover, in a T cell restimulation assay, XmAb808 was able to overcome apparent T cell exhaustion promoted by xaluritamig, strongly recovering xaluritamig's reduced anti-tumor activity weeks into the assay. The addition of targeted costimulation translated to superior T cell-mediated cytotoxicity in vitro and markedly improved anti-tumor responses in humanized xenograft models, highlighting XmAb808's potential to synergize with TCE-based immunotherapies."

Bispecific • Clinical • IO biomarker • Oncology • Ovarian Cancer • Prostate Cancer • Solid Tumor • BCL2L1 • CD276 • CLDN6 • STEAP1

Precision-Engineered CD3 T-Cell Engagers for Solid Tumours: Conditional Activation, Microenvironment Modulation, and Clinical Translation. (PubMed, Cancers (Basel)) - "Next-generation TCE platforms integrating conditional activation, cytokine payloads, and checkpoint modulation-deployed with biomarker-guided selection and TME-modulating combinations-represent a transformative therapeutic strategy. With tarlatamab's phase III survival benefit establishing clinical proof-of-concept, and pivotal trials underway for xaluritamig and next-generation agents, TCEs are positioned to become standard-of-care platform therapies in biomarker-defined solid tumours by 2028-2030."

IO biomarker • Journal • Review • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Hematological Disorders • Hematological Malignancies • Lung Cancer • Oncology • Prostate Cancer • Small Cell Lung Cancer • Solid Tumor • DLL3 • HAVCR2 • LAG3 • PD-1 • STEAP1