P3, N=532, Completed, Dendreon | Active, not recruiting --> Completed

IFN-β responses to TLR1/2 signaling correlated with increased numbers of IFN-β producing T cells after broad, tumor antigen independent stimulation. Thus, peripheral innate immunity differs by race, may predict survival after sip-T, and associates with peripheral T cell functionality in men with mCRPC.

The presence of T-cells specific for the PAP target antigen was detectable in 6/10 (60%) individuals with nmCSPC, and 3/5 (60%) individuals with nmCRPC, many years after immunization. The detection of immune responses to the vaccine target years after immunization suggests durable immunity can be elicited in patients using a DNA vaccine encoding a tumor-associated antigen.Trial Registration: NCT00582140 and NCT00849121.

P2, N=26, Recruiting, H. Lee Moffitt Cancer Center and Research Institute | Trial primary completion date: Oct 2025 --> Oct 2024

P2, N=19, Active, not recruiting, University of Wisconsin, Madison | Trial completion date: Nov 2024 --> Dec 2027

P1/2, N=12, Terminated, Hookipa Biotech GmbH | N=70 --> 12 | Trial completion date: Sep 2026 --> Apr 2024 | Recruiting --> Terminated | Trial primary completion date: Sep 2024 --> Apr 2024; Decision by the company to terminate the H-300-001 study early for non-safety related reasons.

P1, N=12, Recruiting, University of Oklahoma | Trial completion date: May 2024 --> Nov 2024 | Trial primary completion date: May 2024 --> Nov 2024

The data suggest that immune correlates in blood differ in AA and non-AA with mCRPC pre- and post-sipuleucel-T.

P2, N=61, Active, not recruiting, University of Wisconsin, Madison | Recruiting --> Active, not recruiting

P2, N=60, Recruiting, University of Wisconsin, Madison | Trial completion date: Dec 2025 --> Oct 2026 | Trial primary completion date: Mar 2024 --> Jan 2025

P1, N=12, Recruiting, University of Oklahoma | Trial completion date: Feb 2024 --> May 2024 | Trial primary completion date: Feb 2024 --> May 2024

Evaluation of tumor-infiltrating lymphocytes revealed a 2-14-fold higher influx of sip-T and a significant increase in IFN-γ producing CD8+ T cells and NKT cells within the tumor microenvironment (TME) in the IL-15 group. In conclusion, we put forward evidence that IL-15 treatment can enhance the functional antitumor immunity of sip-T, providing rationale for combining IL-15 or IL-15 agonists with sip-T to treat patients with mCRPC.

P2, N=26, Recruiting, Yale University | Not yet recruiting --> Recruiting

P1/2, N=70, Recruiting, Hookipa Biotech GmbH

P1, N=12, Recruiting, University of Oklahoma | Trial completion date: Jul 2027 --> Feb 2024 | Trial primary completion date: May 2024 --> Feb 2024

This is the first study to evaluate the sip-T product using CyTOF, and the first pre-clinical in vivo prostate tumor modeling of sip-T. IL-15 treatment significantly enhances anti-tumor efficacy, effector immune cell activation and tumor infiltration, and reverses key mediators of immune suppression. Studies with modified IL-15 cytokines are ongoing and will be presented.

P1, N=12, Recruiting, University of Oklahoma | Not yet recruiting --> Recruiting | Initiation date: Oct 2023 --> Jan 2024

P2, N=19, Active, not recruiting, University of Wisconsin, Madison | Trial completion date: Nov 2023 --> Nov 2024

Provenge (sipuleucel-T) is an autologous cancer-vaccine-based immunotherapy approved for men with asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC)...Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Sample collection and DC isolation Basic Protocol 2: Determination and application of fluid shear stress Basic Protocol 3: Flow cytometry analysis of DCs after FSS stimulation.

P2, N=60, Recruiting, University of Wisconsin, Madison | Trial primary completion date: Dec 2023 --> Mar 2024

P3, N=400, Not yet recruiting, Dendreon

P2, N=26, Not yet recruiting, Yale University

P3, N=450, Active, not recruiting, Dendreon | Trial completion date: May 2023 --> Feb 2024 | Trial primary completion date: May 2023 --> Dec 2023

Since regulatory approval of the vaccine therapy sipuleucel-T in the biomarker-unselected population, there has not been much success with immunotherapy treatment in advanced prostate cancer...On the horizon, novel drugs using bispecific T-cell engager (BiTE) and chimeric antigen receptors (CAR) technology are being explored and have shown promising early efficacy in this disease. Here we discuss the features of the tumour microenvironment that predispose to immune resistance and rational strategies to enhance antitumour responsiveness in advanced prostate cancer.

P1/2, N=66, Completed, University of Wisconsin, Madison | Active, not recruiting --> Completed

Median OS was consistent regardless of whether the agents were administered sequentially or concurrently, including after NDI update. Results suggest that sipuleucel-T induces an immunologic prime-boost effect after initial sipuleucel-T exposure, even when combined with ARTAs.

P2, N=19, Active, not recruiting, University of Wisconsin, Madison | Trial completion date: Jan 2025 --> Nov 2023 | Trial primary completion date: Jan 2024 --> Dec 2022

This activity is supported by educational grants from AstraZeneca Pharmaceuticals LP, Bayer HealthCare Pharmaceuticals, Janssen Biotech Inc, administered by Janssen Scientific Affairs LLC, Lilly, Merck, and Sanofi. Key clinical and biological factors in the selection of therapy for newly diagnosed mCRPC; influence of earlier use of secondary hormonal therapy and chemotherapy on current management approaches Key findings from clinical trial and real-world data sets exploring the efficacy and safety of sipuleucel-T Optimal patient selection for treatment with sipuleucel-T; importance of early identification of appropriate candidates Data sets defining the role of secondary hormonal therapies for patients with mCRPC, including those who have received one of these agents in an earlier disease setting Role of the CDK4/6 pathway in prostate cancer proliferation and resistance to androgen receptor (AR)-targeted therapy Available efficacy and safety findings with CDK4/6 inhibitors for mCRPC Design, eligibility criteria and primary and secondary endpoints of the Phase II/III CYCLONE 2 trial evaluating first-line abiraterone and prednisone with or without abemaciclib for mCRPC

Treatment landscape for metastatic castrate-resistant prostate cancer (mCRPC) has evolved beyond additional agents with ARPI and/or docetaxel, including other treatments with sipuleucel-T, radium, cabazitaxel, PARP inhibitors, and lutetium, which have specific indications and role in sequencing. Novel therapies remain critically needed after progression from lutetium.

Androgen deprivation therapy (ADT) plus Androgen Receptor Target Agents (ARTAs) or docetaxel are the actual standard of care in prostate cancer (PC). Several therapeutic options are available for pretreated patients: cabazitaxel, olaparib, and rucaparib for BRCA mutations, Radium-223 for selected patients with symptomatic bone metastasis, sipuleucel T, and 177 LuPSMA-617...The radionuclide Lu-PSMA-617 proved successful outcomes in pretreated mCRPC patients. Additional studies will better clarify the appropriate candidates to each strategy and the correct treatments' sequence.

In the past decade, new treatment options for mCRPC, including abiraterone, enzalutamide, docetaxel, cabazitaxel, sipuleucel-T, radium-223, Lu-PSMA-617, and Olaparib, have demonstrated a survival benefit in phase 3 trials. Bone-modifying agents have become part of the overall treatment strategy for mCRPC, in which denosumab and zoledronic acid reduce skeletal-related events...Tumors with gene alterations that affect homologous recombination repair, such as BRCA1 and BRCA2 alterations, are sensitive to poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitors in mCRPC. This review sought to highlight recent advances in systemic therapy for mCRPC and strategies to support patient selection and treatment sequencing.

CME Provider and Supporter(s): This event is organized and accredited by Research to Practice and supported through educational grants provided by Astellas and Pfizer Inc, AstraZeneca Pharmaceuticals LP, Bayer HealthCare Pharmaceuticals, Exelixis Inc, Janssen Biotech Inc, administered by Janssen Scientific Affairs LLC, Lilly, Merck, and Sanofi. Key clinical and biologic factors in the selection of therapy for patients with newly diagnosed mCRPC; impact of earlier use of secondary hormonal therapy and chemotherapy on current disease management approaches Key findings from clinical trial and real-world data sets exploring the efficacy and safety of sipuleucel-T; impact of patient age, race, PSA level and other factors on outcomes Optimal patient selection for sipuleucel-T; importance of early identification of candidates Biologic basis for combining PARP inhibitors with antiandrogen therapies for prostate cancer; rationale for the potential activity of these combinations in patients without homologous recombination repair (HRR) gene mutations Available and emerging data (eg, from the PROpel, MAGNITUDE and TALAPRO-2 trials) with PARP inhibitors combined with secondary hormonal agents for previously untreated mCRPC Rationale for the evaluation of CDK4/6 inhibitors among patients with mCRPC Design, eligibility criteria and primary and secondary endpoints of the Phase II/III CYCLONE 2 trial evaluating first-line abiraterone and prednisone with or without abemaciclib for mCRPC; estimated completion date

Most common 1L treatments included enzalutamide (30.7%), abiraterone acetate (29.9%), docetaxel (19.7%), sipuleucel-T (8.9%), and radium-223 (5.2%). HRR alterations were identified in about 1 in 5 tested patients initiating mCRPC treatment. Future studies should focus on understanding alteration testing strategies in diverse clinical practice settings to ensure patients with HRR alterations are identified in a timely manner and receive appropriate clinical management.

Avelumab plus carboplatin has an acceptable safety profile and was associated with a prolonged OS given the heavily pretreated population.

Despite FDA approval of sipuleucel-T in 2010, endeavors to use immune checkpoint inhibitors in unselected prostate cancer patients have not improved clinical outcomes...Cytokine-based therapies present an alternative immune strategy to target the pleiotropic prostate cancer tumor microenvironment beyond T-cells. Future immunotherapy strategies in prostate cancer should address these immune cell populations which may play more important roles in the prostate cancer tumor microenvironment.

To date, eleven BEVS-derived products have been approved for use, including four human vaccines [Cervarix against cervical cancer caused by human papillomavirus (HPV), Flublok and Flublok Quadrivalent against seasonal influenza, Nuvaxovid/Covovax against COVID-19], two human therapeutics [Provenge against prostate cancer and Glybera against hereditary lipoprotein lipase deficiency (LPLD)] and five veterinary vaccines (Porcilis Pesti, BAYOVAC CSF E2, Circumvent PCV, Ingelvac CircoFLEX and Porcilis PCV). As the demand for biotechnology increases, there has been a concomitant effort into optimizing yield, stability and protein glycosylation through genetic engineering and the manipulation of baculovirus vector and host cells. In this review, we summarize the strategies and technological advances of BEVS in recent years and explore how this will be used to inform the further development and application of this system.

Conclusions This is the first comprehensive study to evaluate the composition of sip-T from mCRPC patients using high dimensional CyTOF analysis, and serves as an important reference source for further modification and improvement of sip-T efficacy. Furthermore, our data is the first to show that the addition of IL-15 to sip-T could potentially enhance the efficacy of sip-T in mCRPC patients.

Sipuleucel-T (Provenge) is the first FDA approved immunotherapeutic agent for the treatment of asymptomatic or minimally symptomatic metastatic castrate resistant prostate cancer (mCRPC); demonstrating a benefit in overall survival...There is also a need to adjust strategies to overcome histologic barriers such as tissue hypoxia and dense stroma. The racial differences of immunological responses between men of diverse ethnicities also merit further investigation to improve the efficacy of immunotherapy and better patient selection in prostate cancer.

P2, N=19, Active, not recruiting, University of Wisconsin, Madison | Trial completion date: Oct 2023 --> Jan 2025 | Trial primary completion date: Oct 2022 --> Jan 2024

Sipuleucel-T is the only FDA approved autologous cellular immunotherapy for PCa targeting prostatic acid phosphatase (PAP), showing a 4.1 month survival benefit for metastatic castration-resistant prostate cancer patients...The vaccine induced secretory (IFNγ and TNFα) and cytotoxic CD8+ T cells and effector memory splenic T cells. Conclusions The periphery of patients with PCa exhibits immune responsiveness to the MutPAP42mer peptide and immunization of mice induces/expands T cell-driven, wild-type PAP immunity, and therefore, has the potential to drive protective anti-tumour immunity in patients with PCa.