2141-V11 Antibody for Prostate Cancer

Recruiting at 6 trial locations

Overseen By Karen Autio, MD

Age: 18+

Sex: Male

Trial Phase: Phase 2

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 All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 24 months

99 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new antibody treatment, 2141-V11 (an Fc-engineered anti-CD40 agonist monoclonal antibody), to determine if it can help the immune system eliminate prostate cancer when combined with standard treatments. Researchers aim to discover if this combination can completely eradicate cancer and identify minimal residual disease, which refers to a small number of cancer cells remaining after treatment. Suitable candidates for this trial include men with prostate cancer that is localized or has spread slightly but can be managed with a comprehensive treatment plan. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants, offering them a chance to contribute to significant advancements in prostate cancer 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.

Is there any evidence suggesting that 2141-V11 is likely to be safe for humans?

Research shows that 2141-V11, a treatment designed to help the immune system fight cancer, has been tested in people before. In one study, researchers injected this treatment directly into tumors. The study found that 2141-V11 was generally well-tolerated by patients, with most side effects being mild or moderate.

Since this study is in a later phase, earlier safety tests were positive enough to continue. This indicates the treatment has already shown it can be safe for people. However, as with any treatment, some people may still experience side effects. It's important to discuss any concerns with the study team. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for prostate cancer?

Unlike the standard prostate cancer treatments, which often include surgery, radiation, and hormone therapy, the 2141-V11 antibody is a novel approach. It specifically targets cancer cells, potentially offering a more precise attack on the disease with fewer side effects. Researchers are excited because this antibody could enhance the body's immune response to cancer, possibly leading to better outcomes for patients with different stages of prostate cancer, from intermediate-risk to metastatic. This targeted mechanism sets 2141-V11 apart, making it a promising option in the fight against prostate cancer.

What evidence suggests that combining 2141-V11 with standard treatments could be effective for prostate cancer?

Research shows that the 2141-V11 antibody might help treat cancer. In an earlier study with 12 patients who had advanced cancer, six experienced tumor shrinkage after receiving 2141-V11. This treatment boosts the immune system to attack and destroy cancer cells. In this trial, researchers will divide participants into different cohorts based on their disease stage to evaluate the effectiveness of 2141-V11 in treating prostate cancer. These promising results suggest that 2141-V11 could be useful in treating prostate cancer, especially when combined with standard treatments. Early findings are encouraging and show potential in addressing difficult-to-treat cancers. ^{1 2 3 5 6}

Who Is on the Research Team?

Matthew Dallos, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

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)

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• 2141-V11

Trial Overview 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.

How Is the Trial Designed?

Group I: Cohort C Experimental Treatment 1 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 B Experimental Treatment 1 Intervention

Men presenting with clinically localized or locoregional high-risk disease.

Group III: Cohort A Experimental Treatment 1 Intervention

Men presenting with clinically localized intermediate-risk disease for whom surgery can be safely delayed for neoadjuvant treatment.

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Published Research Related to This Trial

ADC-1013, a fully human agonistic CD40 antibody, effectively activates dendritic cells, leading to enhanced immune responses such as increased secretion of IL12 and upregulation of costimulatory molecules, which are crucial for T-cell activation.

In preclinical models, ADC-1013 demonstrated significant antitumor effects and the ability to induce long-term tumor-specific immunity, suggesting its potential as a novel local immunotherapy for cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The human agonistic CD40 antibody ADC-1013 eradicates bladder tumors and generates T-cell-dependent tumor immunity. Mangsbo, SM., Broos, S., Fletcher, E., et al.[2021]

Modified Fc regions of agonistic anti-human CD40 monoclonal antibodies (mAbs) significantly enhance their effectiveness in a mouse model that expresses human CD40 and IgG receptors.

The study emphasizes the importance of balancing increased treatment efficacy with the potential for secondary side effects, indicating that while modifications can improve outcomes, they may also introduce risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inhibitory IgG Receptor-Expressing Cells: The Must-Have Accessory for Anti-CD40 Immunomodulatory mAb Efficacy. Bruhns, P., Teillaud, JL.[2018]

The study highlights the critical role of the IL-15 pathway in enhancing the effectiveness of CD40 agonist antibodies in treating bladder cancer, particularly by increasing the activation of CD8 T cells in the tumor environment.

Combining anti-CD40 agonist antibodies with exogenous IL-15 significantly boosts anti-tumor activity and promotes long-term immune memory, suggesting a promising new strategy for bladder cancer treatment that warrants further clinical investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

IL-15 synergizes with CD40 agonist antibodies to induce durable immunity against bladder cancer. Wong, JL., Smith, P., Angulo-Lozano, J., et al.[2023]

Using a mouse model that mimics human immune responses, researchers found that anti-CD40 antibodies can cause significant toxicity, similar to what is observed in patients, which helps predict potential side effects in clinical settings.

However, by delivering an Fc-engineered anti-CD40 antibody directly into tumors, the study demonstrated that it is possible to achieve strong antitumor immunity while avoiding the systemic toxicities associated with traditional methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxicity of an Fc-engineered anti-CD40 antibody is abrogated by intratumoral injection and results in durable antitumor immunity. Knorr, DA., Dahan, R., Ravetch, JV.[2019]

The anti-human CD40 monoclonal antibody CP-870,893 can activate antitumor immunity without needing to engage Fc receptors, which is different from other antibody therapies that do require this interaction.

This unique mechanism of action for CP-870,893 suggests it may have advantages in therapeutic applications for cancer treatment, potentially leading to more effective immune responses against tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-human CD40 monoclonal antibody therapy is potent without FcR crosslinking. Richman, LP., Vonderheide, RH.[2021]

The chimeric antibody ch-5C11 against the CD40 molecule can be stably expressed in CHO cells, demonstrating effective production and maintenance of its binding activity to human CD40.

Ch-5C11 effectively inhibits the proliferation of Daudi B lymphoma cells, indicating its potential as a therapeutic agent in targeting CD40-related pathways in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Expression of human-mouse chimeric antibody against CD40 in CHO cell line and characterization of its function]. Qu, QX., Chen, C., Wang, Q., et al.[2017]

Agonistic CD40 monoclonal antibodies (mAb) have shown promise in activating the immune system to generate anticancer responses, potentially offering a new therapeutic option that works differently from traditional immune checkpoint inhibitors like anti-CTLA-4 or anti-PD-1.

Initial clinical trials indicate that agonistic CD40 mAb can produce effective antitumor responses without significant toxicity, suggesting a safe profile for use in cancer treatment, although further research is needed to optimize dosing and administration strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Agonistic CD40 antibodies and cancer therapy. Vonderheide, RH., Glennie, MJ.[2022]

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S1535610825003198

Fc-optimized CD40 agonistic antibody elicits tertiary ... Among 12 metastatic cancer patients, 2141-V11 was well tolerated without dose-limiting toxicities. Six patients experienced tumor reduction, ...

2. mskcc.org mskcc.org/cancer-care/clinical-trials/23-252

A Phase 2 Study of a Presurgical CD40 Agonist (2141-V11 ... Researchers are assessing a new treatment for people with prostate cancer that has not spread but has a high risk of spreading.

3. withpower.com withpower.com/trial/phase-2-prostatic-neoplasms-2-2024-bfd30

2141-V11 Antibody for Prostate Cancer The purpose of this study is to see whether combining 2141-V11 with various standard treatments is an effective treatment approach for prostate cancer.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT06347705

NCT06347705 | A Study of 2141-V11 in Combination With ... The purpose of this study is to see whether combining 2141-V11 with various standard treatments is an effective treatment approach for prostate cancer.

5. trial.medpath.com trial.medpath.com/news/92b103c13bb42ebc/engineered-cd40-antibody-achieves-complete-cancer-remission-in-phase-1-trial

Engineered CD40 Antibody Achieves Complete Cancer ... A modified CD40 agonist antibody called 2141-V11 demonstrated remarkable efficacy in a phase 1 clinical trial, with six of 12 patients experiencing ...

6. cancer.gov cancer.gov/research/participate/clinical-trials/intervention/fc-engineered-anti-cd40-agonist-antibody-2141-v11?pn=1

Clinical Trials Using Fc-engineered Anti-CD40 Agonist ... Review the clinical trials studying fc-engineered anti-cd40 agonist antibody 2141-v11 on this list and use the filters to refine the results by age and ...