2141-V11 for Bladder Cancer

Recruiting at 6 trial locations

Overseen By Eugene Pietzak, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Anticancer therapy, Immunotherapy

Disqualifiers: Muscle-invasive cancer, Metastatic cancer, Autoimmune disease, Active infection, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 2 years

55 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug, 2141-V11 (an Fc-engineered anti-CD40 agonist monoclonal antibody), to determine its safety for individuals with bladder cancer unresponsive to standard treatments. It targets those who cannot or choose not to undergo bladder-removal surgery. Researchers will explore different doses to identify the safest one and assess how the body processes the drug. Individuals with non-muscle invasive bladder cancer not responding to BCG therapy and not undergoing radical cystectomy may be suitable candidates for this trial. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the chance to be among the first to receive this new drug.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, it mentions that you cannot have had certain treatments like chemotherapy or immunotherapy within a few weeks before starting the trial. It's best to discuss your specific 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 new treatment, may help fight bladder cancer by boosting the body's immune system to attack tumors. Early studies suggest it could effectively target cancer cells.

However, researchers are still learning about its safety because it is in the early stages of human testing. This study is among the first to try 2141-V11 in people, especially those whose cancer hasn't responded to other treatments. As a Phase 1 trial, the main goal is to determine if 2141-V11 is safe, so researchers closely monitor any side effects and how well participants handle the treatment.

While detailed safety results aren't available yet, the focus on safety ensures that any side effects will be carefully recorded and addressed. Participants can expect thorough monitoring throughout the trial to ensure their safety. ^{1 2 3 4 5}

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

Unlike the standard treatments for bladder cancer, like surgery, chemotherapy, and BCG therapy, 2141-V11 is an anti-CD40 agonist antibody. This new treatment is unique because it harnesses the immune system by targeting CD40, a protein that enhances immune response, directly attacking cancer cells. Researchers are excited about 2141-V11's potential because it can be delivered directly into the bladder or tumor, potentially making it more effective for patients who cannot undergo radical cystectomy. Additionally, it offers a promising alternative for those who choose to avoid aggressive surgery, aiming for effective results with fewer side effects.

What evidence suggests that 2141-V11 might be an effective treatment for bladder cancer?

Research has shown that 2141-V11, a type of antibody, strengthens the immune system's fight against bladder cancer. This trial will explore different methods of administering 2141-V11, including intravesically or intratumorally, as well as a fixed dose of 10 mg. Studies have found that it boosts immune activity by targeting and activating certain immune cells. Early results suggest that delivering this treatment directly into the bladder may create a strong defense against tumors both locally and throughout the body. Although limited data from human trials exist, 2141-V11 is designed to better engage immune pathways, offering hope for those who haven't responded to other treatments. Initial tests have shown promise in stimulating anti-tumor effects, making it a candidate worth exploring further. ^{1 2 3 5 6}

Who Is on the Research Team?

Bernard Bochner, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with non-muscle invasive bladder cancer (NMIBC) that hasn't improved after standard treatment and who aren't having their bladder surgically removed. Participants must be over 18, in fairly good health, able to follow the treatment schedule, and have had recent exams confirming no cancer in the upper urinary tract. Women of childbearing age need a negative pregnancy test and all participants must agree to use contraception.

Inclusion Criteria

My last bladder examination was within the last 60 days.

My cancer's details were confirmed by the MSK Department of Pathology.

I have completed the necessary BCG therapy.

Exclusion Criteria

I am not currently on any cancer treatments, including experimental drugs.

History or current evidence of any condition, therapy, or laboratory abnormality that might interfere with the subject's participation for the full duration of the trial, interfere with the subject's ability to cooperate with the requirements of the trial, confound the results of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator

I've had bladder treatments between my last bladder exam and starting this trial.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive different doses of 2141-V11 to test safety and tolerability

Up to 2 years

Intravesical or intratumoral administration during standard of care cystoscopy

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

What Are the Treatments Tested in This Trial?

Interventions

• 2141-V11

Trial Overview The study is testing different doses of a new drug called 2141-V11 for safety in people with NMIBC. It's one of the first trials on humans for this drug, which will be delivered directly into the bladder through a catheter. Researchers will also examine how the body processes this medication.

How Is the Trial Designed?

Group I: (Cohort C) expansion cohort 10 mg of 2141-V11 Experimental Treatment 1 Intervention

For patients in Cohort C, 10 mg of 2141-V11 will be administered as an intratumoral injection during standard of care cystoscopy prior to and within four weeks of planned radical cystectomy.

Group II: (Cohort B) 2141-V11, a fixed dose of 10mg Experimental Treatment 1 Intervention

For patients who are ineligible for radical cystectomy or have elected not to undergo the procedure.

Group III: (Cohort A) anti-CD40 antibody 2141-V11 Experimental Treatment 1 Intervention

Intravesically or intratumorally) of an anti-CD40 agonist antibody (2141-V11) for the treatment of subjects with BCG-unresponsive NMIBC who are considered ineligible for or have elected not to undergo radical cystectomy.

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Pin Down Bladder Cancer Research Foundation

Collaborator

Trials

1

Recruited

60+

Rockefeller University

Collaborator

Trials

162

Recruited

16,700+

Published Research Related to This Trial

The study highlights the importance of the IL-15 pathway in enhancing the effectiveness of CD40 agonist antibodies in treating bladder cancer, showing that this combination can lead to increased activation of CD8 T cells and improved antitumor responses.

Using humanized models, the research demonstrates that combining anti-CD40 agonist antibodies with exogenous IL-15 can optimize therapeutic outcomes, 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]

Engagement of the inhibitory FcγRIIB receptor is crucial for the antitumor activity of human CD40 monoclonal antibodies, as demonstrated in a mouse model humanized for FcγRs and CD40.

Engineering Fc variants to enhance binding to FcγRIIB while avoiding FcγRIIA significantly boosts antitumor immunity, emphasizing the importance of optimizing the Fc domain in therapeutic antibodies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic Activity of Agonistic, Human Anti-CD40 Monoclonal Antibodies Requires Selective FcγR Engagement. Dahan, R., Barnhart, BC., Li, F., et al.[2021]

Local delivery of anti-CD40 antibodies showed superior antitumor effects compared to systemic delivery in bladder cancer models, highlighting the importance of CD8 T cells in tumor growth inhibition.

This local approach resulted in reduced toxicity and less accumulation of antibodies in the liver, suggesting it could be a safer and more effective treatment option for patients with advanced solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Locally delivered CD40 agonist antibody accumulates in secondary lymphoid organs and eradicates experimental disseminated bladder cancer. Sandin, LC., Orlova, A., Gustafsson, E., et al.[2022]

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]

Intravesical delivery of anti-CD40 agonist antibodies in mouse models of bladder cancer shows promising antitumor effects, reducing exhausted CD8+ T cells and enhancing immune responses, indicating a potential new therapy for high-risk non-muscle-invasive bladder cancer (NMIBC).

The fully human, Fc-enhanced anti-CD40 agonist antibody (2141-V11) demonstrated robust antitumor activity without systemic toxicity in both treatment-naïve and treatment-refractory settings, suggesting it could be a safe and effective alternative to current BCG therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dendritic cell targeting with Fc-enhanced CD40 antibody agonists induces durable antitumor immunity in humanized mouse models of bladder cancer. Garris, CS., Wong, JL., Ravetch, JV., et al.[2022]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05126472

NCT05126472 | Study of 2141-V11 in People With Non ... The purpose of this study is to test the safety of the study drug 2141-V11 in people whose NMIBC did not respond to standard treatment, and who will not ...

2. urotoday.com urotoday.com/conference-highlights/aua-2024/aua-2024-bladder-cancer/151759-aua-2024-phase-i-study-of-intravesical-fc-optimized-anti-cd40-agonist-antibody-2141-v11-for-non-muscle-invasive-bladder-cancer-nmibc-unresponsive-to-bacillus-calmette-guerin-bcg.html

AUA 2024: Phase I Study of Intravesical Fc-Optimized Anti ... Dr. Bernard Bochner presented the results of a phase 1 study of intravesical Fc-optimized anti-CD40 agonist antibody 2141-V11 for non-muscle invasive bladder ...

3. asco.org asco.org/abstracts-presentations/ABSTRACT367290

Phase I study of intravesical anti-CD40 agonist antibody ... We engineered a fully-human anti-CD40 agonist antibody (2141-V11) with optimized Fc binding to FcγRIIB, which demonstrates significantly enhanced CD40 agonist ...

4. 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 ... Find clinical trials studying fc-engineered anti-cd40 agonist antibody 2141-v11 ... A Study of 2141-V11 for the Treatment of Bladder Cancer. Status: Active.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8325152/

Intravesical dendritic cell targeting with Fc-enhanced CD40 ... Intravesical delivery of Fc-optimized CD40 agonistic antibodies drives potent local and systemic anti-tumor immunity against bladder cancer.

6. delta.larvol.com delta.larvol.com/Products/?ProductId=3877c730-9f7c-4052-aab2-4ac97fc23811

2141-V11 / Memorial Sloan-Kettering Cancer Center, ... Phase 1/1b trial of Fc-engineered Anti-CD40 Agonist Monoclonal Antibody (2141-V11) infused with D2C7-IT in enhancing disease by Convection-Enhanced Delivery ...