Pluvicto (lutetium Lu 177 vipivotide tetraxetan) / Novartis, Otsuka - LARVOL DELTA

Real-world outcomes among patients with metastatic castration-resistant prostate cancer (mCRPC) receiving guideline-recommended therapies after treatment with 177Lu-PSMA-617: A real-world prostate cancer disease observation (PRECISION) data platform analysis. (ASCO-GU 2025) - "Guideline-recommended therapies included abiraterone, enzalutamide, darolutamide, apalutamide, cabazitaxel, docetaxel, pembrolizumab, sipuleucel-T, niraparib, olaparib, talazoparib, rucaparib, and radium-223. In this real-world analysis, the majority of patients who received guideline-recommended therapies after 177Lu-PSMA-617 achieved at least a PSA50 response, suggesting that 177Lu-PSMA-617 treatment does not preclude response to other subsequent therapies."

Clinical • Metastases • Real-world • Real-world evidence • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Advancing Treatment in mCRPC: What Radiation and Nuclear Medicine Specialists Should Know About PLUVICTO, the First and Only PSMA-Targeted Therapy NOW APPROVED Prior to Chemotherapy (SNMMI 2025) - "Not for distribution. 3 the key efficacy and safety data from the PSMAfore study and review patient cases who are eligible for PLUVICTO therapy."

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

Assuring Staff Safety with Radiopharmaceuticals: Multidisciplinary Education Awareness Across Institutional Sites (ONS 2025) - "Significance & Background: On March 23, 2022, the Federal Drug Administration approved 177 Lu-PSMA-617 therapy for prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer (mCRPC) who failed taxane-based chemotherapy... By educating all staff who may be exposed to radiopharmaceutical patients, we ensure compliance with Nuclear Regulatory Guidelines for the use of radioactive materials including adherence to the Code of Federal Regulations "Standards for Protection Against Radiation". Staff will be monitored to ensure an 80% compliance rate for completion. Additional education on radiation safety post radiopharmaceutical infusion will be included in the mandatory 2025 annual educational bundle for all staff and in orientation programs for new hires."

Clinical • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Probabilistic causal network models from real-world prostate cancer data identify potential synergistic combinations with CBP/P300 inhibitors (AACR 2025) - "Given that both PSMA-radioligand therapies and PARP inhibitors induce DNA damage or inhibit DNA repair, we hypothesize that these drugs in combination with pocenbrodib would lead to additive or synergistic effects by enhancing the PARPi and PSMA-radioligand efficacy via their known mechanisms of action.To validate these hypotheses, we treated a panel of 5 genetically-diverse prostate cancer PDX-derived organoids with pocenbrodib, the PARPi olaparib, and in combination. Addition of a low dose of pocenbrodib to a single dose of Lu177-PSMA617 (60 MBq) led to better tumor growth inhibition control than either single agent on its own. Mechanistic analyses from RNAseq are ongoing.Together, our integrated omics and experimental analyses support the hypothesis that combination of pocenbrodib with DNA damage-inducing or -inhibiting targeted therapies may provide further therapeutic benefit to prostate cancer patients than single agent therapies alone."

Clinical • Real-world • Real-world evidence • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • BRCA2

DNA polymerase theta inhibitor, ART6043, potentiates the efficacy of 177Lu- and 225Ac-based radioligand therapies in vitro and in vivo (AACR 2025) - "This potential is pertinent to cancer therapy, as radioligand therapy (RLT), where a radionuclide is targeted to tumour cells by linking to peptides binding tumour-specific receptors, has had recent clinical success, in particular with 177Lu-PSMA-617 for prostate cancer. Key findings were confirmed for the combination of ART6043 with 225Ac-RLT.Furthermore, in vivo studies in mouse prostate cancer xenografts showed that the combination of ART6043 with 177Lu-RLT induced significant tumour growth inhibition and a significant improvement in median survival with regimens that were well tolerated. This work supports the clinical development of the combination of ART6043 with RLT to improve the clinical efficacy of RLT."

Preclinical • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • POLQ

Uncovering the mechanisms of action of 177Lu- and 212Pb- based PSMA radioligand therapies (AACR 2025) - "Introduction: 177Lu-PSMA-617 is the first FDA-approved targeted radioligand therapy (RLT), and in clinical trials, significantly prolonged survival and improved quality of life in patients with metastatic castration resistant prostate cancer (mCRPC). Comparison studies of 177Lu- and 212Pb-PSMA treatment on PC cells showed a higher efficacy of 212Pb-PSMA in vitro and in vivo supporting the clinical application of 212Pb-PSMA for mCRPC. Mechanistic studies furthered the understanding of PC radiobiology and cellular responses to beta- and alpha-RLT with the identification of a cell cycle arrest in PC specifically induced by 212Pb-PSMA."

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

Prostate cancer lineage states detected by circulating tumor cell RNA sequencing are prognostic biomarkers for overall survival and resistance to androgen receptor pathway inhibitors and177Lutetium-PSMA-617 (AACR 2025) - "We report the largest CTC RNA-seq cohort of patients with metastatic prostate cancer and demonstrate that high-purity CTC RNA-seq identifies prostate cancer lineage states mirroring those in tissue, including an NE phenotype concordant with small cell/neuroendocrine histology. We also identified a more common LumB phenotype defined by persistent AR signaling and high proliferation and associated with poor prognosis and poor response to 177Lu-PSMA-617."

Biomarker • Circulating tumor cells • Clinical • Tumor cell • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Prostate specific membrane antigen targeted PRMT5 inhibition re-sensitizes cancer cells to radiation therapies (AACR 2025) - "Although treatment with the targeted radioligand therapy, 177Lu-PSMA-617 (Pluvicto®) has significantly improved outcomes of patients who progress on androgen deprivation therapy, development of resistance to Pluvicto via upregulation of DNA damage repair enzymes has remained a major impediment to achievement of complete responses...Not surprisingly, co-administration of PSMA-PRMT5i similarly increased the efficacy of beam radiation from 50% to 90% tumor suppression at the same concentration (10 nmol/mouse/day). Because no therapeutic benefit could be detected in mice treated with the same concentration of nontargeted PRMT5i, and since no loss in animal body weight was observed in any of the treatment groups, we conclude that low dose PSMA-PRMT5i can significantly improve radiation therapies outcomes with little or no accompanying toxicity."

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

ATNM-400 is a novel Actinium-225 antibody radioconjugate with strong efficacy in preclinical models of prostate cancer (AACR 2025) - "ATNM-400 showed strong anti-tumor efficacy and a favorable safety profile in preclinical PCa models. These results highlight ATNM-400's potential as a transformative therapeutic option for PCa patients with unmet clinical needs."

Preclinical • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • FOLH1

A novel nanobody-based radionuclide drug conjugate (RDC) platform through introducing a human serum albumin (HSA) binder by the intelligent ligase-dependent conjugation (iLDC) technology: an innovative and versatile approach for next-generation RDCs with enhanced pharmacokinetics and druggability (AACR 2025) - "The novel RDC platform combining iLDC technology with a unique HSA-binding linker-chelator design can generate 177Lu-NBC-02 with an extended circulation half-life, higher tumor uptake and lower salivary gland uptake in both CDX model and mCRPC patients compared to Pluvicto®. The IND enabling of this potential BIC anti-PSMA RDC is underway for the exploration of therapeutic effects on the treatment of mCRPC. Furthermore, the applied strategy provides a promising next-generation platform for future RDC discovery which requires nanobody as a targeting carrier, hence significantly expanding promise beyond the current format."

PK/PD data • Castration-Resistant Prostate Cancer • Oncology • Prostate Cancer

Preclinical development of MHB048C: A novel anti-PSMA ADC with a potent topoisomerase I inhibitor (AACR 2025) - "The FDA's approval of (177) Lu-PSMA-617 has validated PSMA as a therapeutic target for treating metastatic castration-resistant prostate cancer (mCRPC). In GLP monkey studies, MHB048C exhibited a favorable safety profile with no off-target toxicities. The highest non-severely toxic dose (HNSTD) was determined to be 45 mg/kg Q3W, the maximum dose tested.In conclusion, MHB048C demonstrated potent anti-tumor activity both in vitro and in vivo, along with a favorable safety profile, supporting advancement to clinical development."

Preclinical • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • FOLH1

NCCN has published updates to the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines), and the NCCN Radiation Therapy Compendium for Prostate Cancer, Version 2.2025. (NCCN)

NCCN guideline • Prostate Cancer

Illuccix for 68-Ga PSMA-11 Imaging for the Staging of Prostate Cancer | Sponsored by: Telix Pharmaceuticals (AUA 2025) - "Understanding the clinical of 68-Ga-PSMA-11 (Illuccix) PET/CT imaging for initial staging of prostate cancer, biochemical recurrence and for the selection of patients for whom Lu177-PSMA-617 is indicated. Reviewing patient case studies illustrating the clinical utility of Illuccix for urology patients. Gaining an understanding of the method of action for Illuccix and the radiographic PET/CT findings."

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

PSMA-delay castration (DC): an open-label, multicenter, randomized phase 3 study of [177Lu]Lu-PSMA-617 versus observation in patients with metachronous PSMA-positive oligometastatic prostate cancer (OMPC) (AUA 2025) - No abstract available

Clinical • Metastases • P3 data • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Distinct Neuroendocrine Subtypes in Castration-Resistant Prostate Cancer as Prognostic Markers for Targeted Therapy (AUA 2025) - "Uncovering lineage plasticity within NEPC subtypes could improve treatment options, especially with the new FDA-approved 177Lu-PSMA-617 radiopharmaceutical therapy... The shift from adenocarcinoma to neuroendocrine lineage in CRPC indicates an adaptive resistance to therapies. Detecting lethal NEPC phenotypes earlier could enable tailored precision treatments, paving the way for improved outcomes in CRPC."

Biomarker • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Neuroendocrine Tumor • Oncology • Prostate Cancer • Solid Tumor • MYCN • STMN1

Health-related quality of life, pain and safety outcomes in the Phase 3 PSMAfore study of 177Lu-PSMA-617 in patients with metastatic castration-resistant prostate cancer (AUA 2025) - P3 | "Post-hoc analyses of PSMA-positive, taxane-naive patients with mCRPC who received 177Lu-PSMA-617 showed a delayed time to first SSE, with or without a concomitant BPA, and longer TTW in patient-reported HRQoL and pain. 177Lu-PSMA-617 led to shorter median time to improvement after worsening in pain intensity and a favorable safety profile compared with ARPI change."

Clinical • HEOR • Metastases • P3 data • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Pain • Prostate Cancer • Solid Tumor

225Ac-J591 PSMA-Targeted Radionuclide Therapy in Metastatic Castration-Resistant Prostate Cancer Patients with Prior 177Lu-PSMA Therapy (AUA 2025) - P2 | "INTRODUCTION AND OBJECTIVE: Prostate-specific membrane antigen -targeted radioligand therapy (PSMA-TRT) with 177Lu-PSMA-617 is a validated approach; however, response rates vary, and disease progression is nearly inevitable. PSMA-targeted alpha radionuclide therapy using 225Ac-J591 has efficacy in patients with mCRPC despite prior 177Lu-PSMA. Common clinical prognostic factors are associated with poorer outcomes. A multicenter study is enrolling patients with and without prior 177Lu-PSMA to validate these findings [NCT06549465]."

Clinical • Metastases • Anemia • Castration-Resistant Prostate Cancer • Fatigue • Genito-urinary Cancer • Hematological Disorders • Neutropenia • Oncology • Pain • Prostate Cancer • Solid Tumor • Thrombocytopenia

Transcriptomic Profiling of the Tumor Immune Microenvironment Reveals Prognostic Markers in mCRPC Patients Treated with LuPSMA Therapy (AUA 2025) - "INTRODUCTION AND OBJECTIVE: The full potential of [177Lu]Lu-PSMA-617 (LuPSMA) therapy remains unclear, with various factors likely influencing its effectiveness... For treatment-naive patients, PD-L2 is a negative prognostic indicator, whereas M1/M0 macrophages are a positive factor. In patients who underwent biopsy after starting systemic treatment, significant alterations in the TME were noted, with tumor inflammation being a negative prognostic marker in those receiving LuPSMA therapy."

Biomarker • Clinical • IO biomarker • Castration-Resistant Prostate Cancer • Oncology • Prostate Cancer • AR • PD-L2

Visceral metastases, platelet dynamics, and PSA decline: from biomarkers to better outcomes in [177Lu]Lu‑PSMA‑617 therapy in metastatic castration-resistant prostate cancer. (PubMed, Theranostics) - " By combining three factors-visceral metastases, platelet count variation, and PSA reduction-patients could be stratified into distinct prognostic groups as early as after the first cycle. These findings pave the way for personalized management and enhanced clinical outcomes for mCRPC patients receiving [177Lu]Lu-PSMA-617."

Biomarker • Journal • Retrospective data • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Prostate-specific membrane antigen (PSMA) expression in primary and metastatic renal cell cancer (UroCCR-65 study). (PubMed, EJNMMI Res) - P | "PSMA showed high expression in metastases of ccRCC."

Journal • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Kidney Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • FOLH1

Deutsche Bank lifts Novartis stock target to CHF115 on Pluvicto optimism (Investing.com) - "On Thursday, Deutsche Bank (ETR:DBKGn)’s analyst Emmanuel Papadakis increased the price target for Novartis shares...to CHF115.00, up from the previous CHF110.00, while maintaining a Buy rating for the pharmaceutical giant. The company, with a market capitalization of $214 billion and impressive year-to-date returns of 16.5%, currently appears undervalued according to InvestingPro Fair Value analysis. This adjustment reflects a more optimistic outlook for Novartis’ revenue growth, particularly due to the recent developments surrounding its cancer treatment, Pluvicto....The upward revision of the price target comes after a prostate cancer expert call held by Deutsche Bank, which provided insights into the market’s reception of Pluvicto’s label expansion....The new price target of CHF115 represents a 5% increase from the previous target and is based on a 15 times forward-year 2025 core price-to-earnings ratio."

Stock price • Castration-Resistant Prostate Cancer

Evaluating PICOs Requested by Member States During Scoping for EU HTA Versus Those Covered in Actual HTAs (ISPOR 2025) - "We aimed to assess the alignment between PICOs identified in EUnetHTA 21 scoping surveys for PLUVICTO®, EBVALLO® and POMBILITI™ published in 2023, versus PICOs considered in actual HTAs of these products. Published HTAs for PLUVICTO, EBVALLO and POMBILITI conducted to date (January 6, 2025) were identified and reviewed. PICOs included in actual HTAs were predicted by the EUnetHTA 21 scoping exercise; however, there may be over-scoping of PICOs due to the scoping process and requirement to meet all member states' needs. This may place an unnecessary burden on manufacturers responding to irrelevant PICOs and manufacturer input into the scoping of EU JCAs could be beneficial"

LuCAB: Cabazitaxel in Combination With 177Lu-PSMA-617 in Metastatic Castration-resistant Prostate Cancer (clinicaltrials.gov) - P1/2 | N=35 | Active, not recruiting | Sponsor: Peter MacCallum Cancer Centre, Australia | Recruiting ➔ Active, not recruiting

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

Dr Dorff on the Safety of Lutetium Lu 177 Vipivotide Tetraxetan in mCRPC With Renal Impairment (OncLive) - "Looking ahead, Dorff added that it would be of interest to include a larger and more diverse patient population. She explained that other City of Hope centers in the United States, including Georgia, Arizona, and Illinois, could help provide a more geographically diverse outcomes when those data are included. Assessing these broader data may also open the door for additional questions and help identify whether the results will change because of a larger and more geographically diverse patient population treated with lutetium Lu 177 vipivotide tetraxetan, Dorff concluded."

Video

Genomic Profiling and Treatment Response in Metastatic Castration-Resistant Prostate Cancer Patients Treated with 177Lu-PSMA-617 (Pluvicto) (PSMA 2025) - No abstract available

Clinical • Metastases • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor