Adoptive Cell Therapy for Bladder Cancer

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: H. Lee Moffitt Cancer Center and Research Institute

Must not be taking: Immunosuppressants, Chemotherapy

Disqualifiers: HIV, Hepatitis B/C, Autoimmune, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

Duration: 3 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for non-muscle invasive bladder cancer using adoptive cell therapy with tumor-infiltrating lymphocytes (TIL). The goal is to determine if this approach, which uses special immune cells to target cancer, is safe and manageable for patients. It targets those whose bladder cancer did not respond well to a previous treatment called BCG and who can handle medical procedures well. Participants will have their own immune cells collected, grown in a lab, and then reintroduced into their bladder to target cancer cells. This trial may suit those who have shown visible signs of bladder cancer after BCG treatment and meet other health criteria. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

Will I have to stop taking my current medications?

The trial requires that you stop using any immunosuppressive medications, like corticosteroids, at least 14 days before joining. However, certain types of corticosteroids, like inhaled or topical ones, are allowed. If you're on other medications, the protocol doesn't specify, so it's best to discuss with the trial team.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that adoptive cell therapy, which uses special immune cells known as tumor-infiltrating lymphocytes (TIL), holds potential for treating various cancers, including bladder cancer. These cells are studied for their ability to locate and destroy cancer cells. Past patients demonstrated that TIL therapy can be well-tolerated, with manageable side effects.

In studies where TILs were delivered directly into the bladder, the treatment was generally safe and accepted by patients. The most common side effects were mild, such as bladder irritation, which is typical for bladder cancer treatments.

Since this trial is in an early stage, it primarily focuses on assessing the safety and tolerability of the treatment. Researchers closely monitor the treatment for any possible side effects. While some evidence suggests that TIL therapy is safe, this study will provide more detailed information specifically for bladder cancer patients. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for bladder cancer, which often involve surgery, chemotherapy, or radiation, adoptive cell therapy with tumor-infiltrating lymphocytes (TIL) offers a novel approach by using the body's own immune cells to fight the cancer. Researchers are excited because this therapy involves taking TIL from bladder tumors, expanding them significantly in the lab, and reintroducing them into the bladder, potentially enhancing the body's natural ability to target and destroy cancer cells. The use of interleukin-2 (IL-2) to culture and expand these cells is also unique, as it amplifies the immune response more effectively than current therapies. This method could provide a more personalized and potentially less invasive treatment option for bladder cancer patients.

What evidence suggests that Adoptive Cell Therapy with Tumor-infiltrating Lymphocytes might be an effective treatment for bladder cancer?

Research shows that adoptive cell therapy, which uses special immune cells known as tumor-infiltrating lymphocytes (TILs), holds promise for treating bladder cancer. In this trial, participants will receive TIL therapy, where TILs are propagated and cultured with interleukin-2 (IL-2) to exceed 30 million cells. Studies have found that TILs can effectively locate and attack cancer cells in the bladder. The success rate for TIL therapy is high, with 75% to 97% of treatments successfully growing these immune cells. Early results suggest that this method can significantly shrink tumors in some patients. The therapy involves taking a person's own immune cells, growing and multiplying them outside the body, and then reintroducing them to more aggressively target cancer cells. This evidence supports the potential effectiveness of TIL therapy for non-muscle invasive bladder cancer. ^{1 2 3 4 6}

Who Is on the Research Team?

Michael Poch, MD

Principal Investigator

Moffitt Cancer Center

Are You a Good Fit for This Trial?

This trial is for individuals who have been treated with BCG for high-grade non-muscle invasive bladder cancer (NMIBC) and show evidence of the disease. They must be in good health, understand the study, and consent to participate. Key eligibility includes a performance status of 0-1, adequate organ function, no recent intravesical chemotherapy or immunosuppressive drugs, no uncontrolled illnesses or certain infections like HIV or hepatitis B/C.

Inclusion Criteria

My bladder cancer is mostly urothelial and hasn't spread deep into the muscle.

I can provide a tissue sample for the trial, either from a needed treatment or a low-risk procedure.

I have a high-grade bladder cancer but haven't had muscle invasion, and I'm fit for participation.

Exclusion Criteria

Any condition that, in the opinion of the investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study results

I've been cancer-free for 2 years, except for certain early-stage or in situ cancers.

I haven't needed IV antibiotics for infections in the last week.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive intravesical adoptive cell therapy using TIL, administered four times over three weeks

3 weeks

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 months

Long-term follow-up

Participants are monitored for progression-free survival and overall response rate

12 months

What Are the Treatments Tested in This Trial?

Interventions

• Adoptive Cell Therapy with Tumor-infiltrating Lymphocytes (TIL)

Trial Overview The trial is testing adoptive cell therapy using TIL (tumor infiltrating lymphocytes) delivered directly into the bladder to see if it's safe and tolerable for treating urothelial cell carcinoma in NMIBC patients who have previously received BCG therapy.

How Is the Trial Designed?

Group I: Treatment with Adoptive Cell Therapy Experimental Treatment 1 Intervention

TIL from bladder biopsies will be propagated and cultured with interleukin-2 (IL-2) to a target goal of \>30 million cells. These TIL then undergo rapid clonal expansion (REP) by incubation with anti-CD3 monoclonal antibody (mAb), resulting in \>500-fold expansion. After 4-6 weeks culture time intravesical TIL will be administered via intravesical infusion, consisting of up to 3.2e8 cells in 40 mL aliquot. Intravesical therapy will be administered for up to 2 hours. This treatment will occur four times (Day 0, Day 7, Day 14 and Day 21).

Adoptive Cell Therapy with Tumor-infiltrating Lymphocytes (TIL) is already approved in United States, European Union for the following indications:

Approved in United States as TIL Therapy for:

• Melanoma
• Research trials for other cancers including bladder, breast, ovarian, renal cell, head-and-neck, non-small cell lung cancers, prostate cancer, sarcoma, and pancreatic carcinomas

Approved in European Union as TIL Therapy for:

• Melanoma
• Research trials for other cancers including bladder, breast, ovarian, renal cell, head-and-neck, non-small cell lung cancers, prostate cancer, sarcoma, and pancreatic carcinomas

Who Is Running the Clinical Trial?

H. Lee Moffitt Cancer Center and Research Institute

Lead Sponsor

Trials

576

Recruited

145,000+

United States Department of Defense

Collaborator

Trials

940

Recruited

339,000+

Published Research Related to This Trial

This study successfully expanded tumor-infiltrating lymphocytes (TIL) from 70% of primary bladder tumors and all lymph node metastases, indicating a feasible approach for developing adoptive cell therapy in bladder cancer patients.

The addition of an agonistic 4-1BB antibody enhanced TIL expansion from primary tumors, suggesting a potential strategy to improve the effectiveness of TIL therapy, which could lead to better treatment options for patients with advanced bladder cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Expansion of tumor infiltrating lymphocytes (TIL) from bladder cancer. Poch, M., Hall, M., Joerger, A., et al.[2021]

Adoptive cell therapy using PD-1-expressing tumor-infiltrating lymphocytes (TILs) combined with an anti-PD-1 antibody significantly enhances the anti-tumor response in a melanoma mouse model, demonstrating improved efficacy against solid tumors.

This approach maintains the high specificity of TILs for tumor cells while overcoming limitations posed by the tumor immune microenvironment, suggesting potential for broader application in other cancer therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Coupling programmed cell death 1-positive tumor-infiltrating T cells with anti-programmed cell death 1 antibody improves the efficacy of adoptive T-cell therapy. Chu, J., Wang, C., Ma, Q., et al.[2022]

A 53-year-old melanoma patient developed Guillain-Barré syndrome (GBS) 19 days after receiving tumor-infiltrating lymphocyte (TIL) therapy, highlighting a potential neurological side effect of this immunotherapy.

The patient's GBS was treated successfully, leading to full recovery after 21 months, suggesting that while TIL therapy can have serious side effects, they may be manageable and reversible.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Guillain-Barré syndrome after adoptive cell therapy with tumor-infiltrating lymphocytes. Orcurto, A., Hottinger, A., Wolf, B., et al.[2021]

Adoptive cellular therapy (ACT) using tumor-infiltrating lymphocytes (TILs) showed promising results in treating bladder cancer, with systemic ACT leading to reduced tumor growth and enhanced T cell infiltration in treated mice.

Intravesical delivery of TILs directly into the bladder was effective in controlling tumor growth without the need for prior chemotherapy or interleukin-2, highlighting a potential less invasive treatment option for bladder cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systemic and intravesical adoptive cell therapy of tumor-reactive T cells can decrease bladder tumor growth in vivo. Bunch, BL., Morse, J., Asby, S., et al.[2021]

The TIL 3.0 method, which uses IL-2 combined with agonistic antibodies, significantly enhances the expansion of tumor-infiltrating lymphocytes (TIL) from non-small cell lung cancer (NSCLC) tumors, producing 5.3 times more TIL compared to the traditional TIL 1.0 method.

TIL 3.0 not only increases the quantity of CD8+ TIL but also maintains a diverse T-cell repertoire that closely resembles the original tumor's clonal hierarchy, suggesting a greater potential for effective adoptive cell transfer therapies in NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined IL-2, agonistic CD3 and 4-1BB stimulation preserve clonotype hierarchy in propagated non-small cell lung cancer tumor-infiltrating lymphocytes. Shah, P., Forget, MA., Frank, ML., et al.[2022]

Bladder cancer patients have high levels of myeloid derived suppressor cells (MDSCs) in their urine, which suppress T cell proliferation, indicating a challenging immune environment for treatment.

Intravesical gemcitabine can effectively deplete MDSCs and other immune cells in bladder tumors, enhancing the effectiveness of adoptive cell therapy with T cells, leading to improved anti-tumor responses when used in combination.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting myeloid-derived suppressor cells with gemcitabine to enhance efficacy of adoptive cell therapy in bladder cancer. Bazargan, S., Bunch, B., Ojwang', AME., et al.[2023]

In a study analyzing tumor-infiltrating lymphocytes (TILs) from metastatic melanoma patients, neoantigen-specific CD4+ T cells were found to be crucial, showing effective responses against tumors, even in non-responders.

The research highlights the need to focus on neoantigen-specific CD4+ T cells in adoptive cell therapy (ACT) protocols, as they can enhance antitumor immunity and provide a potent source of tumor-specific effectors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoantigen-specific CD4+ tumor-infiltrating lymphocytes are potent effectors identified within adoptive cell therapy products for metastatic melanoma patients. Hall, MS., Teer, JK., Yu, X., et al.[2023]

Adoptive cell therapy (ACT) using tumor-infiltrating lymphocytes (TILs) has shown promising results in treating melanoma and may be applicable to other cancers, but its clinical development faces challenges such as therapeutic resistance and treatment-related toxicity.

Ongoing research is focused on enhancing the efficacy of TIL-based ACT by improving the selection and manufacturing of tumor-reactive TILs, which could help overcome current limitations and expand its use in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tumor-infiltrating lymphocytes for adoptive cell therapy: recent advances, challenges, and future directions. Granhøj, JS., Witness Præst Jensen, A., Presti, M., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05768347

NCT05768347 | Intravesical Adoptive Cell Therapy w/ TIL ... The purpose of the study is to evaluate the feasibility, safety and tolerability of intravesical adoptive cell therapy using TIL (tumor infiltrating ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10669950/

Tumor-Infiltrating Lymphocytes and Adoptive Cell Therapy The success rate of TIL outgrowth is currently very high and varies from 75 % [4] to 97 % [20]. The CD3 antibody targets the CD3 complex of the T cell receptor ...

3. jitc.bmj.com jitc.bmj.com/content/8/2/e001673

Systemic and intravesical adoptive cell therapy of tumor- ... Adoptive cellular therapy (ACT) using tumor-infiltrating lymphocytes (TILs) has potential to treat bladder cancer, as previously demonstrated ...

4. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2023-02379

Intravesical Adoptive Cell Therapy (ACT) with Tumor ... This phase I clinical trial tests the safety and side effects of adoptive cell therapy (ACT) with tumor infiltrating lymphocytes (TIL) given within the bladder ...

5. bmcbioinformatics.biomedcentral.com bmcbioinformatics.biomedcentral.com/articles/10.1186/s12859-023-05241-z

Identification and validation of tumor-infiltrating lymphocyte ... This study aimed to research TIL-related genes (TILRGs) and create a gene model to predict BCa patients' overall survival.

6. cell.com cell.com/cell-reports-medicine/fulltext/S2666-3791(25)00089-8

Safety and efficacy of combined treatment with tumor- ... In this report, we describe the results of the clinical trial TILT-T215 combining oncolytic adenovirus TILT-123 with TIL therapy in patients ...