2141-V11 for Bladder Cancer

Recruiting at 6 trial locations

Overseen by Bernard Bochner, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

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

Trial Summary

What is the purpose of this trial?

This trial is testing a new drug called 2141-V11 in people with bladder cancer that didn't respond to other treatments and who won't have surgery. The drug is delivered directly into the bladder to see if it is safe.

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.

What data supports the effectiveness of the drug 2141-V11 for bladder cancer?

Research shows that the drug 2141-V11, when combined with IL-15, can enhance the immune system's ability to fight bladder cancer by activating important immune cells. This combination has shown promising results in preclinical models, suggesting it could be effective in treating bladder cancer. ^{1 2 3 4 5}

Is the treatment 2141-V11 generally safe for humans?

The treatment 2141-V11, also known as an Fc-engineered anti-CD40 agonist monoclonal antibody, has shown potential safety concerns when given systemically, such as liver toxicity and immune-related side effects. However, delivering it directly into the tumor may reduce these toxic effects and still provide effective treatment. ^{1 2 3 4 6}

How is the drug 2141-V11 different from other bladder cancer treatments?

The drug 2141-V11 is unique because it is an Fc-engineered anti-CD40 agonist monoclonal antibody that targets the CD40 receptor on immune cells, enhancing the body's immune response against bladder cancer. Unlike traditional treatments, it can be administered locally to reduce systemic toxicity and is designed to work in combination with IL-15 to boost long-term immunity. ^{1 3 4 5 6}

Research Team

Bernard Bochner, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• 2141-V11 (Virus Therapy)

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.

Participant Groups

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+

Lisa M. DeAngelis

Memorial Sloan Kettering Cancer Center

Chief Medical Officer since 2021

MD from Columbia University

Selwyn M. Vickers

Memorial Sloan Kettering Cancer Center

Chief Executive Officer since 2022

MD from Johns Hopkins University

Pin Down Bladder Cancer Research Foundation

Collaborator

Trials

1

Recruited

60+

Rockefeller University

Collaborator

Trials

162

Recruited

16,700+

Richard P. Lifton

Rockefeller University

Chief Executive Officer since 2016

MD, PhD

Barry S. Coller

Rockefeller University

Chief Medical Officer since 2016

MD

Findings from Research

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]

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]

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

IL-15 synergizes with CD40 agonist antibodies to induce durable immunity against bladder cancer. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Therapeutic Activity of Agonistic, Human Anti-CD40 Monoclonal Antibodies Requires Selective FcγR Engagement. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

IL-15 synergizes with CD40 agonist antibodies to induce durable immunity against bladder cancer. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Locally delivered CD40 agonist antibody accumulates in secondary lymphoid organs and eradicates experimental disseminated bladder cancer. [2022]

5. United States 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. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Toxicity of an Fc-engineered anti-CD40 antibody is abrogated by intratumoral injection and results in durable antitumor immunity. [2019]