2141-V11 Antibody for Prostate Cancer
Recruiting in Palo Alto (17 mi)
+6 other locations
Age: 18+
Sex: Male
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Memorial Sloan Kettering Cancer Center
Must not be taking: Corticosteroids, Antiretrovirals, Seizure medications, others
Disqualifiers: Prior prostate surgery, Brain metastasis, Active infection, others
No Placebo Group
Prior Safety Data
Trial Summary
What is the purpose of this trial?The purpose of this study is to see whether combining 2141-V11 with various standard treatments is an effective treatment approach for prostate cancer. 2141-V11 works by activating the immune system to find and kill cancer cells. Researchers will look at whether this treatment approach is able to completely get rid of cancer in participants, and they will check for the presence of minimal residual disease (MRD) in participants. MRD is a small number of cancer cells that can be detected in the body after treatment.
Do I need to stop taking my current medications for the trial?
The trial does not specify if you need to stop taking your current medications, but it mentions that medications affecting the response to immunotherapy or those lowering the seizure threshold must be stopped or changed at least 4 weeks before starting the treatment. It's best to discuss your current medications with the trial team.
What evidence supports the effectiveness of the drug 2141-V11 for prostate cancer?
Research shows that similar CD40 agonist antibodies have been effective in treating other cancers, like bladder cancer, by activating the immune system to fight tumors. The drug 2141-V11, which is a type of CD40 agonist antibody, has shown promise in preclinical studies for enhancing immune responses and reducing tumor growth.
12345Is the 2141-V11 antibody generally safe for humans?
Research on similar antibodies shows that while there can be side effects like platelet and liver issues, these can be reduced by injecting the treatment directly into the tumor. Initial trials have shown promising results without severe side effects.
13567How is the drug 2141-V11 different from other prostate cancer treatments?
The drug 2141-V11 is unique because it is an Fc-engineered anti-CD40 agonist monoclonal antibody that activates the immune system to fight cancer, unlike other treatments that often block immune checkpoints. It is designed to stimulate immune cells directly, potentially offering a new way to treat prostate cancer with reduced systemic toxicity by using local administration.
13567Eligibility Criteria
Men over 18 with prostate cancer who have not had certain treatments or surgeries for it. They must be able to consent, have a targetable lesion on MRI, and agree to use contraception if sexually active. Excluded are those with recent experimental therapy, significant heart disease, inability to undergo MRI, known metastases in specific organs, inflammatory bowel disease, HIV under certain conditions, seizure risks, severe allergies or liver impairment.Inclusion Criteria
My blood, liver, and kidney tests from the last 28 days show they are working well.
My cancer's T stage was documented within the last 3 months.
Willing and able to provide written informed consent and Authorization for Use and Release of Health and Research Study Information (HIPAA authorization)
+5 more
Exclusion Criteria
Prior experimental therapy for prostate cancer within 30 days of planned Cycle 1 of 2141-V11
I have a serious heart condition.
Significant medical condition other than cancer that would prevent consistent and compliant participation in the study
+14 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive intratumoral injections of 2141-V11, potentially in combination with androgen deprivation therapy, prior to radical prostatectomy
24 months
Follow-up
Participants are monitored for safety and effectiveness after treatment, including assessment of complete response or minimal residual disease
4 weeks
Participant Groups
The trial is testing the effectiveness of a new antibody called 2141-V11 when combined with standard prostate cancer treatments. It aims to activate the immune system against cancer cells and will measure success by checking for minimal residual disease – tiny amounts of cancer that might remain after treatment.
3Treatment groups
Experimental Treatment
Group I: Cohort CExperimental Treatment1 Intervention
Men presenting with low-volume metastatic disease for whom a multimodality therapeutic approach including removal of the primary has the potential to eliminate all disease.
Group II: Cohort BExperimental Treatment1 Intervention
Men presenting with clinically localized or locoregional high-risk disease.
Group III: Cohort AExperimental Treatment1 Intervention
Men presenting with clinically localized intermediate-risk disease for whom surgery can be safely delayed for neoadjuvant treatment.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Memorial Sloan Kettering Bergen (Limited Protocol Activities)Montvale, NJ
Memorial Sloan Kettering Monmouth (Limited protocol activities)Middletown, NJ
Memorial Sloan Kettering Suffolk-Commack (Limited protocol activity)Commack, NY
Memorial Sloan Kettering Westchester (Limited Protocol Activities)Harrison, NY
More Trial Locations
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Who Is Running the Clinical Trial?
Memorial Sloan Kettering Cancer CenterLead Sponsor
References
Agonistic CD40 antibodies and cancer therapy. [2022]Recent success in cancer immunotherapy has reinvigorated the hypothesis that the immune system can control many if not most cancers, in some cases producing durable responses in a way not seen with many small-molecule drugs. Agonistic CD40 monoclonal antibodies (mAb) offer a new therapeutic option which has the potential to generate anticancer immunity by various mechanisms. CD40 is a TNF receptor superfamily member expressed broadly on antigen-presenting cells (APC) such as dendritic cells, B cells, and monocytes as well as many nonimmune cells and a range of tumors. Agonistic CD40 mAb have been shown to activate APC and promote antitumor T-cell responses and to foster cytotoxic myeloid cells with the potential to control cancer in the absence of T-cell immunity. Thus, agonistic CD40 mAb are fundamentally different from mAb which block negative immune checkpoint such as anti-CTLA-4 or anti-PD-1. Initial clinical trials of agonistic CD40 mAb have shown highly promising results in the absence of disabling toxicity, both in single-agent studies and in combination with chemotherapy; however, numerous questions remain about dose, schedule, route of administration, and formulation. Recent findings about the role played by the IgG isotype and the Fc gamma receptor (FcγR) in mAb cross-linking, together with insights into mechanisms of action, particularly with regard to the role of myeloid cells, are predicted to help design next-generation CD40 agonistic reagents with greater efficacy. Here, we will review the preclinical and clinical data and discuss the major issues facing the field.
IL-15 synergizes with CD40 agonist antibodies to induce durable immunity against bladder cancer. [2023]CD40 is a central co-stimulatory receptor implicated in the development of productive anti-tumor immune responses across multiple cancers, including bladder cancer. Despite strong preclinical rationale, systemic administration of therapeutic agonistic antibodies targeting the CD40 pathway have demonstrated dose limiting toxicities with minimal clinical activity to date, emphasizing an important need for optimized CD40-targeted approaches, including rational combination therapy strategies. Here, we describe an important role for the endogenous IL-15 pathway in contributing to the therapeutic activity of CD40 agonism in orthotopic bladder tumors, with upregulation of trans-presented IL-15/IL-15Rα surface complexes, particularly by cross-presenting cDC1s, and associated enrichment of activated CD8 T cells within the bladder tumor microenvironment. In bladder cancer patient samples, we identify DCs as the primary source of IL-15, however, they lack high levels of IL-15Rα at baseline. Using humanized immunocompetent orthotopic bladder tumor models, we demonstrate the ability to therapeutically augment this interaction through combined treatment with anti-CD40 agonist antibodies and exogenous IL-15, including the fully-human Fc-optimized antibody 2141-V11 currently in clinical development for the treatment of bladder cancer. Combination therapy enhances the crosstalk between Batf3-dependent cDC1s and CD8 T cells, driving robust primary anti-tumor activity and further stimulating long-term systemic anti-tumor memory responses associated with circulating memory-phenotype T and NK cell populations. Collectively, these data reveal an important role for IL-15 in mediating anti-tumor CD40 agonist responses in bladder cancer and provide key proof-of-concept for combined use of Fc-optimized anti-CD40 agonist antibodies and agents targeting the IL-15 pathway. These data support expansion of ongoing clinical studies evaluating anti-CD40 agonist antibodies and IL-15-based approaches to evaluate combinations of these promising therapeutics for the treatment of patients with bladder cancer.
The human agonistic CD40 antibody ADC-1013 eradicates bladder tumors and generates T-cell-dependent tumor immunity. [2021]Local administration of immune-activating antibodies may increase the efficacy and reduce the immune-related adverse events associated with systemic immunotherapy of cancer. Here, we report the development and affinity maturation of a fully human agonistic CD40 antibody (IgG1), ADC-1013.
Inhibitory IgG Receptor-Expressing Cells: The Must-Have Accessory for Anti-CD40 Immunomodulatory mAb Efficacy. [2018]In this issue of Cancer Cell, Dahan and colleagues demonstrate that modified Fc regions of agonistic anti-human CD40 mAbs can drastically increase their efficiency in a mouse pre-clinical model expressing human CD40 and IgG receptors. This study also highlights the fine balance between increased treatment efficacy and secondary side effects.
Toxicity of an Fc-engineered anti-CD40 antibody is abrogated by intratumoral injection and results in durable antitumor immunity. [2019]Immune stimulation has emerged as a promising approach to the treatment of neoplastic diseases. Currently approved therapeutics, such as anti-CTLA4 and anti-PD1, are primarily aimed at blocking inhibitory signaling by immune cells. An alternative and potentially synergistic approach would involve activation of immune pathways by agonism of stimulatory receptors, such as CD40. Agonistic antibodies, while promising in principle, have encountered significant barriers in clinical trials limited by the systemic toxicity of such approaches. Using a mouse model humanized for both Fc receptors and CD40, we previously demonstrated enhanced antitumor activity with an Fc-modified antibody. We now demonstrate that this model recapitulates the platelet and hepatic toxicities seen with anti-CD40 antibodies in patients, providing a predictive measure of the dose-limiting activity of this approach. We further show that such toxicity can be circumvented and durable systemic antitumor immunity achieved by intratumoral delivery of an Fc-engineered anti-CD40 agonistic antibody.
Anti-human CD40 monoclonal antibody therapy is potent without FcR crosslinking. [2021]Antibody agonists targeting tumor necrosis factor (TNF) superfamily receptors, including CD40, are being tested therapeutically as anticancer agents. Studies in mice have shown that anti-CD40 monoclonal antibody (mAb) requires Fc-receptor (FcR) engagement to activate antitumor immunity. In contrast, we have reported that clinically active anti-human CD40 mAb CP-870,893 does not require FcR crosslinking, a finding with translational implications.
[Expression of human-mouse chimeric antibody against CD40 in CHO cell line and characterization of its function]. [2017]To investigate the stable expression of a chimeric antibody against CD40 moleculeèch-5C11éin CHO and its biological activity.