ADXS-504 Immunotherapy for Prostate Cancer
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Male
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: Mark Stein
Must not be taking: LHRH agonists, Antiandrogens
Disqualifiers: Metastatic disease, Brain metastasis, Autoimmune, others
No Placebo Group
Trial Summary
What is the purpose of this trial?
Primary Objective: - To evaluate the safety and tolerability of ADXS-504 and to determine the MTD (maximum tolerated dose) or RP2D (recommended phase two dose) Secondary Objectives: * To characterize the immunological activity of ADXS-504, administered as; and to characterize the genomic profiles of study subjects * To evaluate the effects of ADXS-504 on change in PSA * To evaluate time to PSA progression
Will I have to stop taking my current medications?
The trial requires that you stop taking certain medications before enrolling. Specifically, you must not have used LHRH agonists or antagonists within 6 months, oral antiandrogens within 3 months, or certain other agents like 5 alpha reductase inhibitors and systemic steroids within the past month.
What data supports the effectiveness of the treatment ADXS-504 for prostate cancer?
Is ADXS-504 immunotherapy safe for humans?
Immunotherapy treatments for prostate cancer, including those similar to ADXS-504, have generally shown minimal toxicity in early clinical trials, suggesting they are relatively safe for humans. Common side effects reported in similar treatments include fatigue, diarrhea, and infusion reactions, but these are typically not severe.678910
How is the treatment ADXS-504 different from other prostate cancer treatments?
ADXS-504 is a novel immunotherapy for prostate cancer that aims to enhance the body's immune response against cancer cells, which is different from traditional treatments like hormone therapy or chemotherapy. Unlike these standard treatments, ADXS-504 specifically targets the immune system to recognize and attack prostate cancer cells, potentially offering a new option for patients with tumors that are less responsive to conventional therapies.14111213
Eligibility Criteria
Men over 18 with recurrent prostate cancer after primary therapy like surgery or radiation, not on active treatment for other cancers. They must have a stable performance status, adequate organ function, and rising PSA levels according to specific criteria. Participants need to provide consent and health information release, agree to contraceptive guidance if applicable, and cannot have brain metastases or severe autoimmune diseases.Inclusion Criteria
I had initial treatment for prostate cancer and any follow-up treatment was over 6 months ago.
I am 18 years old or older.
I am a man and will use birth control during and for 4 months after treatment.
See 9 more
Exclusion Criteria
Known allergy to study formulation components
History of listeriosis
Implanted medical device posing high risk for bacterial colonization
See 12 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive ADXS-504 monotherapy with dose escalation to evaluate safety and tolerability
4 weeks
Weekly visits (in-person)
Follow-up
Participants are monitored for safety and effectiveness after treatment
4 weeks
Treatment Details
Interventions
- ADXS-504 (Immunotherapy)
Trial OverviewThe trial is testing ADXS-504 immunotherapy in men with recurring prostate cancer. It aims to find the safest dose that patients can tolerate (MTD) or recommend for future studies (RP2D), measure immune response effects of the drug, observe changes in PSA levels, and assess time until PSA levels rise again.
Participant Groups
1Treatment groups
Experimental Treatment
Group I: ADXS-504 Monotherapy Dose EscalationExperimental Treatment1 Intervention
Subjects with Biochemically Recurrent Prostate Cancer will receive ADXS-504 with dose escalation schema.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Columbia University Irving Medical CenterNew York, NY
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Who Is Running the Clinical Trial?
Mark SteinLead Sponsor
References
Integrating Immunotherapies in Prostate Cancer. [2022]In recent years, immunotherapy has emerged as a viable and promising treatment for prostate cancer. Beyond sipulecuel-T, phase III trials are evaluating multiple vaccine and immune-based therapies in men with this disease. Evidence suggests that many of these therapies are effective at augmenting immune responses and slowing tumor growth rates. Yet prospective data evaluating these responses as surrogates for survival are still needed. In the absence of validated intermediate markers of response, growing data suggests that patients with more indolent disease are more likely to benefit from immunotherapies. In order to further optimize immunotherapy use, ongoing trials are evaluating its combination with traditional as well as other immune-based treatments. Preliminary data from these trials are promising and are shedding new light on this area.
Immunotherapy in prostate cancer: review of the current evidence. [2022]Prostate cancer is the most common male malignancy in the Western world. Once it metastasizes, it is incurable. The current gold standard for metastatic disease is the combined docetaxel/prednisone regimen. Prostate cancer shows several characteristics that make it a suitable candidate for immunotherapy, as recently exemplified by the approval of sipuleucel-T, the first vaccine to treat any malignancy. Here, we review different tumor-associated antigen immunotherapy strategies currently being investigated, from a humanized radiolabeled monoclonal antibody (J-591) that targets radiation into tumor cells, moving on to vaccines and through to immunomodulator agents such as anti-CPLA-4 and anti-PD-1 monoclonal antibodies that activate T-cell responses via immune checkpoint inhibition. We explore different opinions on the best approach to integrate immunotherapy into existing standard therapies, such as androgen-deprivation therapy, radiotherapy or chemotherapy, and review different combination sequences, patient types and time points during the course of the disease to achieve a lasting immune response. We present data from recent phase III clinical trials that call for a change in trial endpoint design with immunotherapy agents, from the traditional tumor progression to overall survival and how such trials should include immune response measurements as secondary or intermediate endpoints to help identify patient clinical benefit in the earlier phases of treatment. Finally, we join in the recent questioning on the validity of RECIST criteria to measure response to immunotherapeutic agents, as initial increases in the size of tumors/lymph nodes, which are part of a normal immune response, could be categorized as disease progression under RECIST.
Therapeutic vaccines for prostate cancer: recent advances and future directions. [2018]In recent years, therapeutic cancer vaccines have emerged as a viable and promising treatment for prostate cancer. Beyond sipuleucel-T, phase III trials are evaluating multiple vaccine platforms in men with this disease. Growing data evaluating vaccine therapies suggests that these agents are more effective in patients with more indolent and possibly also earlier stages of disease. In addition, a wealth of preclinical data has shown that traditional prostate cancer treatments including anti androgens, cytotoxic and radiation therapies may provide immunologic synergy when given in combination with vaccine platforms. Building off this data, numerous clinical trials are evaluating therapeutic cancer vaccines in early stage prostate cancer and also in combination with traditional prostate cancer therapies. In addition, in order to optimize immune responses, ongoing trials are evaluating vaccines in combination with immune checkpoint inhibitors. Preliminary data from these trials have been promising and are offering an exciting glimpse at the future of immunotherapy for this disease.
Immune checkpoint B7-H3 protein expression is associated with poor outcome and androgen receptor status in prostate cancer. [2022]Novel immune checkpoint-based immunotherapies may benefit specific groups of prostate cancer patients who are resistant to other treatments.
Current immunotherapeutic strategies in prostate cancer. [2007]For men who have hormone-refractory prostate cancer, current treatment options are somewhat limited, with docetaxel the only agent showing a significant prolongation of survival. Several groups have investigated therapeutic approaches involving stimulation of an immune response against progressive prostate cancer. Several features of prostate cancer suggest that it may be a good target for immunotherapy. Constant pressure by the immune system forces tumors to evolve multiple ways to escape immune assault, however, and it is thus unlikely that single-agent immunotherapy for prostate cancer will achieve maximal clinical benefit. Most likely, successful immunotherapy will eventually require either the combination of multiple immunologic approaches or the combination of immunologic approaches with conventional therapy.
Update: immunological strategies for prostate cancer. [2021]Prostate cancer is the second most common cause of cancer-related death in US men. Along with initial therapy using surgery, radiotherapy, or cryotherapy, hormonal therapy is the mainstay of treatment. For men with advanced (metastatic) disease, docetaxel-based chemotherapy is US Food and Drug Administration (FDA)-approved, and provides a significant survival advantage. This relative paucity of treatment options drives an ongoing quest for additional treatment modalities; among these is immunotherapy. The concept that prostate cancer is a malignancy that can be targeted by the immune system may seem counterintuitive; certainly kidney cancer and melanoma are more traditionally thought of as immune responsive cancers. However, prostate cancer arises in a relatively unique organ and may express a number of proteins (antigens) against which an immune response can be generated. More importantly, several of these agents have now demonstrated a significant survival benefit in randomized controlled clinical trials, and one agent in particular (Sipuleucel-T, Dendreon Corporation, Seattle, WA) could be FDA-approved in 2010. This update summarizes recent clinical developments in the field of prostate cancer immunotherapy, with a focus on dendritic cell vaccines, virus-based vaccines, DNA-based vaccines, and cell-based vaccines. In addition, the notion of agents that target immune checkpoints is introduced. Enthusiasm for prostate cancer immunotherapy is founded upon its potential to mediate targeted, specific, tumor cell destruction without significant systemic toxicity; however, this has yet to be fully realized in the clinical arena.
Efficacy and safety of immune checkpoint inhibitors for patients with prostate cancer: a systematic review and meta-analysis. [2023]Immunotherapy has revolutionized the treatment paradigm of many cancers, however, its effectiveness in prostate cancer patients is still under question. In the present systematic review and meta-analysis, we sought for assessing the efficacy and safety of Immune checkpoint inhibitors (ICIs) in patients with prostate cancer. PubMed, Scopus, Web of Science, and EMBASE databases were searched on Aguste 19, 2022. Thirty five studies met the eligibility criteria. The median overall survival (mOS) of all treatments was 14.1 months, with the longest and shortest mOS was seen among patients who received anti-CTLA-4 monotherapy and anti-PD-1/PD-L1+anti-CTLA-4 regimen at 24.9 and 9.2 months, respectively. Noteworthy, all types of adverse events had the lowest incidence in the anti-PD-1/PD-L1 monotherapy group. Considering the ICI monotherapy regimens, we found that fatigue, diarrhea, and infusion reaction had the highest incidence rates. Future studies evaluating the efficacy and safety of novel combination therapies with ICIs are warranted.
Immunotherapy for prostate cancer: False promises or true hope? [2018]Prostate cancer is the most commonly diagnosed cancer, and the second leading cause of cancer-related death for men in the United States. Despite the approval of several new agents for advanced disease, each of these has prolonged survival by only a few months. Consequently, new therapies are sorely needed. For other cancer types, immunotherapy has demonstrated dramatic and durable treatment responses, causing many to hope that immunotherapies might provide an ideal treatment approach for patients with advanced prostate cancer. However, apart from sipuleucel-T, prostate cancer has been conspicuously absent from the list of malignancies for which immunotherapies have received recent approval from the US Food and Drug Administration. This has left some wondering whether immunotherapy will "work" for this disease. In this review, the authors describe current developments in immunotherapy, including approaches to engage tumor-targeting T cells, disrupt immune regulation, and alter the immunosuppressive tumor microenvironment. The authors then describe the recent application of these approaches to the treatment of prostate cancer. Given the Food and Drug Administration approval of 1 agent, and the finding that several others are in advanced stages of clinical testing, the authors believe that immunotherapies offer real hope to improve patient outcomes for men with prostate cancer, especially as investigators begin to explore rational combinations of immunotherapies and combine these therapies with other conventional therapies. Cancer 2016;122:3598-607. © 2016 American Cancer Society.
Prostate cancer vaccines in clinical trials. [2020]This review presents important information about the current state of the art for vaccine immunotherapy of prostate cancer. It includes important preclinical research for each of the important prostate cancer vaccines to have reached clinical trials. To date, the only prostate cancer vaccine that has completed Phase III trials and has been approved and licensed by the US FDA is Sipuleucel-T, which immunizes patients against the prostate-associated antigen prostatic acid phosphatase. The benefits and concerns associated with the vaccine are presented. A current Phase III trial is currently underway using the vaccinia-based prostate-specific antigen vaccine Prostvac-TRICOM. Other immunotherapeutic vaccines in trials include the Ad/prostate-specific antigen vaccine Ad5-prostate-specific antigen and the DNA/prostatic acid phosphatase vaccine. A cellular vaccine, GVAX, has been in clinical trials but has not seen continuous study. This review also delves into the multiple immune regulatory elements that must be overcome in order to obtain strong antitumor-associated antigen immune responses capable of effectively destroying prostate tumor cells.
Immunotherapy for prostate cancer - recent progress in clinical trials. [2007]Prostate cancer is the most common malignancy affecting men in the United States. Traditional therapy with radical prostatectomy or radiation therapy can be curative for localized disease, but metastatic prostate cancer is currently incurable. The only treatments known to prolong survival in patients with metastatic disease are androgen-deprivation therapy and chemotherapy, both of which have significant side effects. Immunotherapy approaches offer hope in providing new treatments to delay disease progression, ideally with fewer side effects. The results from nearly all early immunotherapy clinical trials for prostate cancer conducted to date have shown minimal toxicity, and many have suggested clinical benefit in terms of delaying disease progression. Several phase III clinical trials are currently under way in patients with metastatic, androgen-independent prostate cancer. The current article reviews recent trials evaluating immune-modulating agents, antigen-specific active immunotherapy, and combination therapies in clinical development for the treatment of prostate cancer.
Prostate Cancer Cells Express More Androgen Receptor (AR) Following Androgen Deprivation, Improving Recognition by AR-Specific T Cells. [2018]Androgen deprivation is the primary therapy for recurrent prostate cancer, and agents targeting the androgen receptor (AR) pathway continue to be developed. Because androgen-deprivation therapy (ADT) has immmunostimulatory effects as well as direct antitumor effects, AR-targeted therapies have been combined with other anticancer therapies, including immunotherapies. Here, we sought to study whether an antigen-specific mechanism of resistance to ADT (overexpression of the AR) may result in enhanced AR-specific T-cell immune recognition, and whether this might be strategically combined with an antitumor vaccine targeting the AR. Androgen deprivation increased AR expression in human and murine prostate tumor cells in vitro and in vivo The increased expression persisted over time. Increased AR expression was associated with recognition and cytolytic activity by AR-specific T cells. Furthermore, ADT combined with vaccination, specifically a DNA vaccine encoding the ligand-binding domain of the AR, led to improved antitumor responses as measured by tumor volumes and delays in the emergence of castrate-resistant prostate tumors in two murine prostate cancer models (Myc-CaP and prostate-specific PTEN-deficient mice). Together, these data suggest that ADT combined with AR-directed immunotherapy targets a major mechanism of resistance, overexpression of the AR. This combination may be more effective than ADT combined with other immunotherapeutic approaches. Cancer Immunol Res; 5(12); 1074-85. ©2017 AACR.
Single-Cell Analysis Reveals EP4 as a Target for Restoring T-Cell Infiltration and Sensitizing Prostate Cancer to Immunotherapy. [2022]Immunotherapies targeting immune checkpoint molecules have shown promising treatment for a subset of cancers; however, many "cold" tumors, such as prostate cancer, remain unresponsive. We aimed to identify a potential targetable marker relevant to prostate cancer and develop novel immunotherapy.
From bench to bedside: immunotherapy for prostate cancer. [2021]The mainstay therapeutic strategy for metastatic castrate-resistant prostate cancer (CRPC) continues to be androgen deprivation therapy usually in combination with chemotherapy or androgen receptor targeting therapy in either sequence, or recently approved novel agents such as Radium 223. However, immunotherapy has also emerged as an option for the treatment of this disease following the approval of sipuleucel-T by the FDA in 2010. Immunotherapy is a rational approach for prostate cancer based on a body of evidence suggesting these cancers are inherently immunogenic and, most importantly, that immunological interventions can induce protective antitumour responses. Various forms of immunotherapy are currently being explored clinically, with the most common being cancer vaccines (dendritic-cell, viral, and whole tumour cell-based) and immune checkpoint inhibition. This review will discuss recent clinical developments of immune-based therapies for prostate cancer that have reached the phase III clinical trial stage. A perspective of how immunotherapy could be best employed within current treatment regimes to achieve most clinical benefits is also provided.