Provenge (sipuleucel-T) / Bausch Health - LARVOL DELTA

Synergistic potential of sipuleucel-T in enhancing immunotherapy for metastatic castration-resistant prostate cancer. (PubMed, J Immunother Cancer) - "Given the use of sipuleucel-T as a standard of care backbone, there is emerging interest in combining it with other immunotherapies, hormonal therapies, or chemotherapies to improve its clinical efficacy. This review summarizes past experiences and current knowledge of combining sipuleucel-T with other treatments and explores future approaches to enhance such combinatorial strategies."

Journal • Review • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • ACPP • PSAP

Real-World Treatment Patterns and Survival in Metastatic Castration-resistant Prostate Cancer: A Systematic Review of Observational Studies. (PubMed, Eur Urol Focus) - "The findings showed that ARPIs are the most frequent first- and second-line treatments in mCRPC, and back-to-back ARPI sequencing is also common practice, especially in the USA, despite the availability of therapies beyond ARPIs. The findings highlight the need to optimize treatment beyond systemic hormone therapy in this setting."

HEOR • Journal • Observational data • Real-world evidence • Review • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

The landscape of genitourinary cancer vaccines: clinical advances and future opportunities. (PubMed, J Adv Res) - "Therapeutic cancer vaccines have been proven effective in the treatment of genitourinary cancers, such as Sipuleucel-T (Provenge) and Bacillus Calmette-Guérin (BCG)...Through different platforms (peptides, DNA, RNA, dendritic cells, etc.), therapeutic cancer vaccines can provoke or strengthen anti-tumor immunity with the assistance of cytokines, chemokines as well as other adjuvants to therefore prevent the deterioration of cancer and eradicate tumor cells. Only a limited number of therapeutic genitourinary cancer vaccines have received regulatory approval, indicating that there are still many critical challenges for the clinical translation of cancer vaccines, which mainly focus on finding effective antigens, immunogenic platforms and suitable combinational clinical strategies."

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

Vascular and neurological toxicity profile of Sipuleucel-T: a large-scale real world pharmacovigilance study. (PubMed, Int J Surg) - "The neurological toxicity of Sipuleucel-T is relatively modest. Age (70-80 years) and body weight were identified as independent predictors of cerebrovascular events during treatment, with higher body weight showing a protective effect. This study identifies high-risk population characteristics for Sipuleucel-T-associated cerebrovascular events, providing important data to support clinical safety measures."

Adverse events • Journal • Real-world evidence • Atrial Fibrillation • Cardiovascular • Hematological Disorders • Myocardial Infarction • Thrombosis

PSMAcTION trial-in-progress: a phase II/III randomized trial of [225Ac]Ac-PSMA-617 (225Ac-PSMA-617) versus standard of care in patients with PSMA-positive metastatic castration-resistant prostate cancer who progressed on or after [177Lu]Lu-PSMA therapy (ESMO 2025) - P2/3 | "Background Prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT) [ 177 Lu]Lu-PSMA-617 prolonged radiographic progression-free survival (rPFS) in patients with PSMA-positive metastatic castration-resistant prostate cancer (mCRPC) in the taxane-naive (PSMAfore) and post-taxane (VISION) settings...In phase 3, ∼420 patients will be randomized to 225 Ac-PSMA-617 for ≤ 6 cycles or investigator's choice of SoC (excluding PARP inhibitors and immunotherapy except sipuleucel-T)...Safety follow-up will occur at 56 and 30 days (+7) after the last dose of 225 Ac-PSMA-617 and SoC, respectively, with long-term follow-up for up to 5 years. As of April 2025, the first patient first visit occurred in the Asia-Pacific region."

Clinical • Metastases • P2/3 data • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

177^Lu-PSMA-617 in Combination With Sipuleucel-T for the Treatment of Metastatic Castration-Resistant Prostate Cancer (clinicaltrials.gov) - P1 | N=30 | Not yet recruiting | Sponsor: City of Hope Medical Center

New P1 trial • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Adenocarcinoma • Prostate Cancer • Solid Tumor • ACPP • PSAP

Real-world treatment patterns in patients with metastatic castration-resistant prostate cancer (mCRPC) previously treated with androgen receptor pathway inhibitor (ARPI) or docetaxelProstACT Global: A phase 3 study of Lutetium (Lu177) rosopatamab tetraxetan plus standard of care vs standard of care alone in patients with metastatic castration-resistant prostate cancer (PCF 2025) - "BACKGROUND: Patients with mCRPC whose disease progressed on an ARPI have a poor prognosis, with median overall survival of <2 years (Sayegh, Eur Urol Focus 2023). These real-world data show that ARPIs remain the most common 1L and 2L treatment in patients with mCRPC despite prior ARPI and/or docetaxel alongside androgen deprivation therapy for mHSPC or nmCRPC. TABLE. Treatment regimens by line of therapy in patients with mCRPC 1L regimen (N=510), 2L regimen (N=188), 3L regimen (N=80), n (%) n (%) n (%) ARPI*,† 289 (56.7) ARPI*,† 83 (44.1) Taxane‡ 23 (28.8) Abiraterone 149 (29.2) Abiraterone 35 (18.6) ARPI*,† 21 (26.3) Enzalutamide 124 (24.3) Enzalutamide 34 (18.1) Enzalutamide 10 (12.5) Taxane‡ 86 (16.9) Taxane‡ 50 (26.6) Abiraterone 8 (10.0) Abiraterone + Cabazitaxel + 16 (3.1) Olaparib 9 (4.8) 8 (10.0) Docetaxel Carboplatin 1 Olaparib 16 (3.1) Lutetium-177 7 (3.7) Lutetium-177 6 (7.5) Abiraterone + Sipuleucel-T 15 (2.9) 4 (2.1) Radium-223 5 (6.3) Sipuleucel-T Other..."

Clinical • HEOR • Metastases • P3 data • Real-world • Real-world evidence • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Hormone Sensitive Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor

Tuning TCR Immunotherapy Targeting Prostatic Acid Phosphatase via Catchbond Modifications for Advanced Prostate Cancer (PCF 2025) - "PAP was previously used to develop the first FDA-approved cancer vaccine, Provenge, but the specific epitopes and cognate TCRs were not clearly defined...and O.N.W. are inventors on a PCT titled “Human T cell receptor pairs reactive with HLA-A*02:01 restricted human prostatic acid phosphatase (PAP) epitopes.”"

IO biomarker • Metastases • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • ACPP • HLA-A • PSAP

Combined treatment with radium-223 (RAD) and enzalutamide (ENZ) in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC): Insights from the global REASSURE study (ESMO 2025) - P, P3 | "Incidence of fractures was slightly higher in ALL pts (10%) with fewer pts receiving concomitant BPAs (denosumab 28% and zoledronic acid 13%)...Table: 2401P ENZ/RAD (N=45) ALL Pts (N=1,472) Median time since initial diagnosis of bone metastases to study entry, months 14 23 Median time since castration resistant cancer to study entry, months 7 13 Extent of disease, % Bone only metastases 80 81 Bone metastases + lymph node only 9 13 Disease burden, % 20 metastases but not Superscan 18 20 Superscan 4 6 Laboratory values, median ALP (U/L) 131 133 PSA (ng/mL) 33 59 Prior abiraterone, % 40 48 Prior docetaxel, % 16 39 Prior Sipuleucel-T, % 18 9 Conclusions In this subgroup of pts treated with combined ENZ/RAD in a real-world setting, there was no new safety signal...Pts received ENZ/RAD earlier in the disease course based on time from mCRPC, time from initial diagnosis of bone metastases and prior docetaxel. Fracture incidence was low in ENZ/RAD, and the majority of pts..."

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

Deep and Durable Prostate-Specific Antigen Response Following Comprehensive Involved Site Radiotherapy for Prostate Cancer Oligometastases (ASTRO 2025) - "The types of systemic therapy consisted of 91% androgen deprivation therapy, 66% androgen receptor pathway inhibitor, 9% docetaxel, 3% radium-223, 3% sipuleucel-T, and 3% none. Comprehensive involved site radiotherapy is effective at achieving undetectable PSA in patients with hormone-sensitive oligometastases. Longer-term follow-up is needed to determine if these results are durable."

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

Trial in Progress: Randomized Phase II Trial of Targeted Radiation with No Castration for Treatment of Metastatic Castration-Resistant Prostate Cancer (ASTRO 2025) - "Exclusion criteria include visceral (liver/brain) metastases, prior PSMA RLT or radium-223 treatment, small cell/neuroendocrine prostate cancer, or impending spinal cord compression. Prior PARP inhibitors, sipuleucel-T, or pembrolizumab are allowed. Following ADT discontinuation, patients are randomized 1:1 into two arms: (1) PSMA RLT (177Lu vipivotide tetraxetan) for 2 cycles with intervening SBRT in 1–5 fractions delivered to all sites of active disease, or (2) the same treatment but with daily transdermal testosterone gel initiated if post-treatment imaging is consistent with no active sites of disease... This trial challenges the conventional indefinite ADT paradigm in mCRPC by assessing whether a non-hormonal approach combining PSMA RLT and SBRT without ongoing testosterone suppression can improve oncologic outcomes and quality of life. If successful, this study may establish a novel treatment framework for mCRPC management."

Clinical • Metastases • P2 data • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Neuroendocrine Tumor • Oncology • Prostate Cancer • Solid Tumor • AR

Study of Sipuleucel-T With or Without Continuing New Hormonal Agents in Metastatic Prostate Cancer (clinicaltrials.gov) - P2 | N=26 | Recruiting | Sponsor: H. Lee Moffitt Cancer Center and Research Institute | Trial primary completion date: Aug 2025 ➔ Dec 2025

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

Prostate Cancer Immunotherapy: Time to Move Beyond Checkpoint Inhibitors. (PubMed, Immunotargets Ther) - "Prior to the advent of ICIs, prostate cancer had one of the first approvals for cancer immunotherapy with sipleucel-T, an anti-cancer vaccine...Most notably, clinical trials with bispecific T-cell engagers (BiTEs) targeting tumor antigens like STEAP-1 and KLK2 have shown clinical promise. Moving beyond ICIs may lead to new approaches to alter the prostate cancer tumor immune microenvironment and improve clinical outcomes."

Checkpoint inhibition • Journal • Review • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • KLK2 • STEAP1

Chimeric Antigen Receptor-Engineered (CAR)-T Cell Therapy for Metastatic Prostate Cancer. (PubMed, Cancer Lett) - "These include androgen receptor signaling inhibitors such as enzalutamide and abiraterone acetate, taxane-based chemotherapies including docetaxel and cabazitaxel, and bone-targeting radiopharmaceuticals like radium-223. Immunotherapeutic agents have also contributed to expanding treatment options with Sipuleucel-T, a dendritic cell-based vaccine, and pembrolizumab, a PD-1 immune checkpoint inhibitor approved for select patient populations. Furthermore, the introduction of poly (ADP-ribose) polymerase inhibitors like olaparib and rucaparib, has transformed the therapeutic landscape, particularly for patients with DNA repair deficiencies in metastatic prostate cancer...In this review, we highlight adoptive cellular therapies utilizing CAR-T cells engineered to recognize prostate cancer-specific antigens, aiming to overcome immune evasion mechanisms. We summarize current CAR-T modalities with their limitations and prospects being evaluated in both preclinical and clinical..."

Journal • Review • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Hematological Disorders • Hematological Malignancies • Neuroendocrine Tumor • Oncology • Prostate Cancer • Solid Tumor • DRD

A new frontier in oncology: Understanding the landscape of cancer vaccines. (PubMed, J Oncol Pharm Pract) - "This review explores the diverse platforms and mechanisms supporting cancer vaccines, ranging from prophylactic vaccines such as HPV and hepatitis B vaccines that have significantly reduced virus-related cancers to therapeutic vaccines like Sipuleucel-T and T-VEC that extend survival in prostate cancer and melanoma. In conclusion, cancer vaccines offer a less toxic, more precise approach to cancer prevention and treatment. Continued innovation, global collaboration, and infrastructure development are essential to realizing their full potential in improving patient outcomes and reducing the global cancer burden."

IO biomarker • Journal • Review • Genito-urinary Cancer • Hepatitis B • Infectious Disease • Melanoma • Oncology • Prostate Cancer • Solid Tumor

Sipuleucel- T: Understanding the Differences in Outcomes Amongst African American and Caucasian Prostate Cancer Patients. A TriNetX Study (MA-AUA 2025) - No abstract available

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

ProvONE: Metastatic Castrate-Resistant Prostate Cancer Subjects Treated With PROVENGE® + One Infusion of Sipuleucel-T (clinicaltrials.gov) - P2 | N=400 | Recruiting | Sponsor: Dendreon | Not yet recruiting ➔ Recruiting | Phase classification: P3 ➔ P2

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

Immunotherapy in metastatic prostate cancer. (PubMed, Ther Adv Med Oncol) - "Despite these advances, the role of immunotherapy in standard prostate cancer (PCa) management is limited, and Sipuleucel-T is the only approved immunotherapeutic agent...Early phase data for TCE are promising, but the feasibility of adoption of TCEs into the clinic will depend on overcoming neutralising anti-drug antibodies and limiting toxicities. CAR-T cells have demonstrated feasibility and acceptable safety profiles in early phase clinical trials, and it is hoped that the ongoing development of later-generation constructs and therapeutic combinations will enhance outcomes."

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

Combinations of treatments based on radiotherapy or radionuclides to enhance immunotherapy efficacy in advanced prostate cancer: a systematic review. (PubMed, J Cancer Res Clin Oncol) - "We observed that combination of Ipilimumab with stereotactic beam radiotherapy (SBRT) at the dose of 8 Gy performed about 12 days (range 2-21) before immunotherapy was liked with trials with a significative gain in progression-free survival. Furtherly, we described better objective responses when immunotherapies, were associated with SBRT than radionuclides An exception was 177Lu-PSMA-617, which showed promising synergic results after few cycles of standard doses, suggesting a possible enhancing of immune system, in particular when associated with anti-PD1 (pembrolizumab). Due to the few data reported in literature, both for radiotherapy and radionuclides, however, future randomized trials should confirm these data."

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

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 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 • Urology

Overall survival outcomes with sipuleucel-T (Sip-T) among Black men with metastatic castrate-resistant prostate cancer (mCRPC) also treated with androgen receptor pathway inhibitors (ARPI). (ASCO 2025) - "Our findings from an investigator-led retrospective analysis independent of sponsors provide independent clinical trial support of prior retrospective findings that suggest Black men with mCRPC who receive Sip-T may have a greater OS than White men. While our analysis controlled for factors that may influence the use of Sip-T, it is limited by potential unmeasured confounders or timing of Sip-T. Further, adequately powered prospective trials specifically evaluating outcomes with Sip-T by race in earlier clinical settings are needed."

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

Overall survival in metastatic castration-resistant prostate cancer (mCRPC): A retrospective electronic medical record analysis of men treated with sipuleucel-T in community urology over 14 years. (ASCO 2025) - "Despite their high-risk disease, patients who received sipuleucel-T had a 44-month median OS, with 28% being alive at 5 years later. This highlights the potential therapeutic benefit of integrating sipuleucel-T into real-world treatment for mCRPC. Further analysis is needed, leveraging the rich nature of this dataset."

Metastases • Retrospective data • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • Urology

Real-world treatment patterns, sequences, and outcomes in patients with mCRPC in US urology clinics. (ASCO 2025) - "Of the 1,914 patients treated with androgen receptor pathway inhibitors (ARPIs) pre-mCRPC, including enzalutamide (enza), abiraterone (abi), apalutamide, and darolutamide, 95.8%, were treated with ARPI ± ADT. This data indicates the majority of patients used ADT alone pre-mCRPC. ARPI rechallenge was the most common treatment sequence from pre-mCRPC to mCRPC among ARPI exposed patients. Less than half of the patients analyzed received 2L+ therapy."

Clinical • HEOR • Real-world • Real-world evidence • Castration-Resistant Prostate Cancer • Prostate Cancer • Urology

Treatment patterns and survival by race among men with metastatic castration-resistant prostate cancer (mCRPC) in the United States: A US electronic medical record database 2020-2023. (ASCO 2025) - "Line of therapy was identified as ARPI, chemotherapy, poly (ADP-ribose) polymerase inhibitors (PARPIs), immunotherapy (pembrolizumab, sipuleucel-T), radiopharmaceuticals (Ra-223, 177Lu-PSMA-RLT), alone or in combination...Overall, ARPI (62%) [abiraterone: 25%; enzalutamide: 24%; apalutamide: 9%; darolutamide 4%] and chemotherapy (22%) [docetaxel 16%; cabazitaxel 6%] were most common first-line treatment (1L Tx) for mCRPC... ARPI and chemotherapy remained the most utilized therapies in mCRPC from 2020 to 2023 in the US. Treatment and survival outcomes did not differ significantly between Whites and AAs in mCRPC. Treatment and survival by race in mCRPC.NE, not evaluable."

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

Focus on urological cancer (ESTRO 2025) - "Clinical trials exploring the combination of brachytherapy with immunotherapies such as nivolumab, pembrolizumab, durvalumab and others are ongoing, with preliminary data indicating improved outcomes in patients with advanced prostate cancer (2, 3)...However, based on the results of phase II trials, no statistically significant improvement in oncological outcomes was observed in patients receiving both sipuleucel-T and radiotherapy (5)...Although combining brachytherapy with immunotherapy holds promise, further research is required to optimise treatment regimens, including dose, fractionation, timing, and sequencing. Prospective clinical trials are critical to better understanding the interaction between these modalities."

IO biomarker • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • Urethral Cancer • Urology