TBio-4101 + Chemo + IL-2 for Skin Cancer

Overseen By Yvonne Nguyen

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: H. Lee Moffitt Cancer Center and Research Institute

Must not be taking: Steroids, Immunosuppressants

Disqualifiers: Heart disease, Immunodeficiency, Pregnancy, others

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

Compensation: Varies

Number of Visits: 3

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment for people with advanced skin cancer, specifically melanoma that cannot be surgically removed or has spread. The study examines the safety and effectiveness of a special immune cell treatment, TBio-4101 (also known as TIDAL-01, a tumor-infiltrating lymphocyte therapy), combined with chemotherapy and interleukin-2 (IL-2) to boost the immune system. Ideal participants are those who have tried standard treatments without success or cannot tolerate them and have been diagnosed with specific types of advanced melanoma. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

Will I have to stop taking my current medications?

The trial requires that any systemic therapy, including anti-cancer monoclonal antibodies, must be stopped at least 4 weeks before starting the lymphodepleting therapy. Additionally, participants taking systemic steroid therapy or immunosuppressive medications are excluded from the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

A previous study on TBio-4101 showed promise for patients with advanced cancers. However, a similar T-cell therapy program was stopped, so researchers are still collecting safety data. This means there might be unknowns about how well people handle TBio-4101.

Interleukin-2 (IL-2) has been used in cancer treatment before. Research has shown it can be helpful, but it also carries risks. High doses of IL-2 can cause side effects, some of which are serious, like low blood pressure or difficulty breathing. These side effects are known, so doctors monitor patients closely.

In this trial, both TBio-4101 and IL-2 are being tested together. The safety of this combination is still under study. Participants will be closely monitored to better understand how their bodies respond. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for skin cancer, which often include surgery, radiation, or chemotherapy, TBio-4101 is a game-changer because it uses a patient's own immune cells to fight the cancer. This approach, known as tumor-infiltrating lymphocyte (TIL) therapy, involves removing immune T-cells from the patient's tumor, multiplying them in the lab, and then reintroducing them into the body to target the cancer more effectively. The addition of Interleukin-2 (IL-2) boosts these T-cells, potentially enhancing their ability to combat cancer cells. Researchers are excited about this treatment because it offers a personalized and potentially more powerful way to attack cancer, paving the way for more effective and tailored therapies.

What evidence suggests that this trial's treatments could be effective for skin cancer?

Research has shown that tumor-infiltrating lymphocyte (TIL) therapy, such as TBio-4101, holds promise for treating advanced melanoma and other solid tumors. This therapy uses the body's immune cells to combat cancer. Studies have found that TIL therapy can shrink tumors and improve outcomes for some patients. In this trial, participants will receive an infusion of TBio-4101 TIL.

Participants will also receive Interleukin-2 (IL-2) after the TIL infusion. IL-2 has been used for years to treat advanced melanoma and has proven effective. Evidence indicates that IL-2 can sometimes lead to complete and lasting cancer remission. Together, these treatments aim to enhance the immune system's ability to fight cancer cells, offering hope for better outcomes in skin cancer treatment. ^{1 6 7 8 9}

Who Is on the Research Team?

Amod Sarnaik, MD

Principal Investigator

Moffitt Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults aged 18-75 with unresectable or metastatic melanoma, including various types like cutaneous and ocular melanoma. Participants must have adequate organ function, an ECOG status of 0 or 1, and be willing to practice birth control. Those with treated brain metastases, a negative pregnancy test (if applicable), and the ability to sign consent can join. Excluded are pregnant women, those with severe heart issues or immunodeficiency disorders, active infections requiring IV antibiotics, history of severe allergies to study drugs, certain lung function impairments, autoimmune diseases needing steroids in the past 6 months.

Inclusion Criteria

I am willing and able to undergo a procedure to collect my blood cells.

I can carry out all my usual activities without help.

My organs and bone marrow are working well.

Exclusion Criteria

You have had a serious allergic reaction to the study drugs in the past.

I am not on steroids or immunosuppressive medications.

I have an autoimmune disease and have been on high-dose steroids in the last 6 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Lymphodepleting Chemotherapy

Participants receive cyclophosphamide and fludarabine to prepare for TIL infusion

7 days

Daily visits for chemotherapy administration

TIL Infusion

Participants receive TBio-4101 TIL product intravenously

1 day

1 visit (in-person)

IL-2 Administration

Participants receive interleukin-2 (IL-2) after TIL infusion

Up to 3 days

Multiple visits (in-person) for IL-2 administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 24 months

What Are the Treatments Tested in This Trial?

Interventions

• Cyclophosphamide
• Fludarabine
• Interleukin-2
• TBio-4101

Trial Overview

The trial tests TBio-4101 therapy using tumor infiltrating lymphocytes after lymphodepleting chemotherapy followed by interleukin-2 (IL-2) in participants with advanced melanoma. It aims to assess if this approach is feasible and safe while also evaluating its effectiveness against the cancer.

How Is the Trial Designed?

Group I: Infusion of TBio-4101 TIL Experimental Treatment 4 Interventions

TBio-4101 is a tumor-infiltrating lymphocyte (TIL) product: participants tumor tissue is surgically removed and immune T-cells are taken out of the tumor and multiplied, or grown, in the laboratory. TIL product infused intravenously over 20 to 30 minutes within 2 to 4 days after the last dose of fludarabine Participants will also receive: * Cyclophosphamide dose 60 mg/kg/day for 2 days administered IV in 250 mL dextrose 5% in water infused simultaneously with Mesna 15 mg/kg/day delivered over 1 hour per day for 2 days. Fludarabine 25 mg/m2/day is delivered by intravenous piggyback daily over 15-30 minutes for 5 days. * Interleukin-2 (IL-2)- will be given to participants through IV after they receive the infusion of the TIL. IL-2 is administered at a dose of 600,000 IU/kg (based on actual body weight) IV every 8-12 hours beginning within 24 hours of TIL infusion for a maximum of 6 doses.

Interleukin-2 is already approved in United States, European Union for the following indications:

Approved in United States as Aldesleukin for:

• Metastatic melanoma
• Metastatic renal cell carcinoma

Approved in European Union as PROLEUKIN for:

• Metastatic renal cell carcinoma

Who Is Running the Clinical Trial?

H. Lee Moffitt Cancer Center and Research Institute

Lead Sponsor

Trials

576

Recruited

145,000+

Turnstone Biologics, Corp.

Industry Sponsor

Trials

7

Recruited

120+

Published Research Related to This Trial

TILs (tumor-infiltrating lymphocytes) from melanoma patients showed good proliferation and targeted cytotoxicity against tumor cells before IL-2 therapy, but their ability to proliferate decreased significantly during and after IL-2 treatment.

Despite the reduced responsiveness of TILs to IL-2 during therapy, there was a notable decrease in live tumor cells in all nine patients studied, indicating that IL-2-based therapies can effectively reduce tumor burden even if TILs become temporarily less responsive.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunological properties of melanoma tumor-infiltrating lymphocytes before and after IL-2-based biotherapies. Itoh, K., Balch, CM., Murray, JL., et al.[2007]

In a study of 31 melanoma patients treated with intralesional IL-2, 32% achieved a pathologic complete response (pCR), which was linked to significantly improved progression-free survival (PFS).

The presence of a higher CD8+ T cell infiltrate in lesions correlated with better treatment outcomes, suggesting that an enhanced immune response may be a key mechanism behind the efficacy of IL-2 therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pathologic complete response to intralesional interleukin-2 therapy associated with improved survival in melanoma patients with in-transit disease. Hassan, S., Petrella, TM., Zhang, T., et al.[2015]

Recombinant interleukin-2 is an effective immunomodulating agent that has shown promising results in treating renal cell carcinoma and melanoma, particularly in patients who do not respond well to conventional therapies.

While it can lead to significant adverse effects like hypotension and renal dysfunction, these effects are generally reversible, and its administration requires careful monitoring in a critical-care setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recombinant interleukin-2: a biological response modifier. Kintzel, PE., Calis, KA.[2007]

In a study of 20 patients with metastatic malignant melanoma previously treated with interleukin-2, 55% achieved an objective partial response to combination chemotherapy (BCDT), indicating that this treatment can still be effective even after IL-2 therapy.

The most common side effect was mild nausea in all patients, but persistent thrombocytopenia limited further treatment, highlighting the need for careful monitoring of blood cell counts during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effective chemotherapy for melanoma after treatment with interleukin-2. Richards, JM., Gilewski, TA., Ramming, K., et al.[2019]

The administration of IL-2 in clinical trials for advanced malignant melanoma shows that the dose and schedule significantly affect both the immune response and the side effects experienced by patients.

Using a standardized dose and schedule of IL-2 across multiple trials allows for better comparison of results regarding toxicity and clinical effectiveness, paving the way for more effective combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interleukin-2 alone and in combination with other cytokines in melanoma: the investigational approach at the University of Texas M.D. Anderson Cancer Center. Parkinson, DR., Talpaz, M., Lee, KH., et al.[2019]

In a phase I clinical trial involving 33 patients with advanced colon cancer or malignant melanoma, recombinant interleukin-2 (rIL-2) was found to enhance immune function, showing significant immune modulation at doses of 1 x 10(7) and 3 x 10(7) U/m2/d, including increased natural killer (NK) activity and lymphocyte counts.

The maximum tolerated dose was established at 3 x 10(7) U/m2/d, with moderate and reversible side effects, and two patients with melanoma achieved partial responses, suggesting that this IL-2 regimen could be a promising approach for immune enhancement in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I clinical trial of recombinant interleukin-2 by periodic 24-hour intravenous infusions. Creekmore, SP., Harris, JE., Ellis, TM., et al.[2017]

In a phase-I study involving 12 melanoma patients, recombinant interleukin 2 (rIL2) was administered safely at doses ranging from 100 to 800 micrograms/m2, with no major organ toxicity observed, although side effects like fever and low serum potassium were noted.

The treatment led to a rapid depletion of peripheral blood lymphocytes followed by a significant rebound in their numbers and enhanced cytotoxicity against tumor cells, indicating a potential immune response, but no major objective tumor responses were achieved.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vivo activation of lymphocytes in melanoma patients receiving escalating doses of recombinant interleukin 2. Gambacorti-Passerini, C., Radrizzani, M., Marolda, R., et al.[2019]

Interleukin-2 (IL-2) is crucial for activating T cells and has shown the ability to induce tumor regressions in both animal models and humans, primarily through the activation of cytotoxic effector cells like lymphokine-activated killer (LAK) cells.

Ongoing Phase I and II trials are investigating various administration methods of IL-2, both alone and in combination with other treatments, to enhance its antitumor effects while managing its dose-related toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The immunotherapy of human cancer with interleukin 2: present status and future directions. Kolitz, JE., Mertelsmann, R.[2019]

In a five-year trial involving 49 patients with relapsing metastatic stage III melanoma, the combination of tumor-infiltrating lymphocytes (TIL) and interleukin-2 (IL-2) did not show a statistically significant improvement in disease-free survival compared to a control group that received no treatment.

The safety profile of TIL + IL-2 was good, with no significant differences in relapse rates or mortality between the treatment and control groups, suggesting that while the treatment was safe, it did not provide the expected benefits over abstention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tumor infiltrating lymphocytes as adjuvant treatment in stage III melanoma patients with only one invaded lymph node after complete resection: results from a multicentre, randomized clinical phase III trial. Khammari, A., Nguyen, JM., Leccia, MT., et al.[2020]

In a study involving 69 patients with metastatic melanoma, unselected young tumor-infiltrating lymphocytes (TILs) showed a higher response rate (35%) compared to CD8(+)-enriched TILs (20%), although the difference was not statistically significant.

The research suggests that unselected young TILs may be more effective and easier to prepare than CD8(+)-enriched TILs, as the latter did not demonstrate superior therapeutic potency despite being more complex to produce.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized selection design trial evaluating CD8+-enriched versus unselected tumor-infiltrating lymphocytes for adoptive cell therapy for patients with melanoma. Dudley, ME., Gross, CA., Somerville, RP., et al.[2021]

Transducing tumor-infiltrating lymphocytes (TILs) with a truncated IL-2 gene allows these cells to produce high levels of IL-2 and proliferate independently, suggesting a promising approach for enhancing adoptive immunotherapy in melanoma treatment.

Although the TILs can initially proliferate autonomously due to the autocrine loop created by IL-2 production, the expression of the IL-2 gene decreases after 2 to 3 weeks, indicating a need for strategies to maintain IL-2 expression over time.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enhanced interleukin-2 production in human tumor-infiltrating lymphocytes engineered by 3'-truncated interleukin-2 gene. Yamaue, H., Kashmiri, SV., De Filippi, R., et al.[2019]

Citations

1.

curemelanoma.org

curemelanoma.org/blog/clinical-trials-to-watch-july-2025

Melanoma Clinical Trials to Watch: July 2025

A cORR rate, defined as sustained shrinkage or disappearance of melanoma, of 56% was observed in the 33 patients. Almost half of the patients ...

2.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC4918260/

Update on use of aldesleukin for treatment of high-risk ...

High-dose interleukin-2 has been used for the treatment of metastatic melanoma since 1998 based on data proving durable complete responses in up to 10% of ...

3.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC5604296/

High-dose interleukin-2 (HD IL-2) for advanced melanoma

PFS and OS analyses. The primary analysis of 243 patients revealed a median OS of 9.6 months (95% CI, 7.4 to 11.2 months) in the entire cohort ...

4.

ar.iiarjournals.org

ar.iiarjournals.org/content/29/10/4189

Single-institution Outcome of High-dose Interleukin-2 (HD ...

Results: Fifteen patients with metastatic melanoma had been treated with HD IL-2. There were 4 patients exhibiting some response, with 1 complete response (CR), ...

5.

jitc.bmj.com

jitc.bmj.com/content/2/1/26

High dose interleukin-2 (Aldesleukin) - expert consensus ...

Recent publications have suggested improved efficacy, perhaps due to improved patient selection based on a better understanding of clinical features predicting ...

6.

ascopubs.org

ascopubs.org/doi/10.1200/jco.2015.33.15_suppl.3053

A retrospective analysis of high-dose aldesleukin (HD IL-2) ...

Conclusions: Early patient data from the PROCLAIM database suggest that HD IL-2 is a safe treatment option for pts who have had progressive ...

7.

clinicaltrials.gov

clinicaltrials.gov/study/NCT00554515

The High-Dose Aldesleukin (IL-2) "Select" Trial for Patients ...

At the present time, IL-2 is the only therapy for kidney cancer that can produce a remission of disease that lasts after treatment is completed. However, most ...

8.

targetedonc.com

targetedonc.com/view/efficacy-and-safety-of-high-dose-interleukin-2-treatment-in-melanoma-patients-with-a-history-of-brain-metastases

Efficacy and Safety of High-Dose Interleukin-2 Treatment in ...

The purpose of this retrospective study is to evaluate tumor response rates and toxicity profiles of IL-2 therapy in a more contemporary cohort of patients ...

9.

molecular-cancer.biomedcentral.com

molecular-cancer.biomedcentral.com/articles/10.1186/s12943-023-01826-7

the promise and pitfalls of IL-2 and IL-2R targeting strategies

In addition, high-dose IL-2, although linked to higher response rates in metastatic melanoma, is associated with increased toxicity [175].