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

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. ^{1 2 3 4 5}

Is 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. ^{1 3 5 6 7}

How 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. ^{1 3 5 6 7}

Research Team

Matthew Dallos, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility 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)

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

References

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

Agonistic CD40 antibodies and cancer therapy. [2022]

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

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

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

The human agonistic CD40 antibody ADC-1013 eradicates bladder tumors and generates T-cell-dependent tumor immunity. [2021]

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

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

5. 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]

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

Anti-human CD40 monoclonal antibody therapy is potent without FcR crosslinking. [2021]

7. China pubmed.ncbi.nlm.nih.gov

[Expression of human-mouse chimeric antibody against CD40 in CHO cell line and characterization of its function]. [2017]