Proof of Concept of TBio-4101, Lymphodepleting Chemo, IL-2 for Relapsed/Refractory Melanoma

NCT05628883 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: MCC-21707
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this first in human study is to evaluate the feasibility, safety, and efficacy of administering TBio-4101 (tumor infiltrating lymphocytes \[TIL\]) after receiving a lymphodepleting chemotherapy regimen and before receiving interleukin-2 (IL-2) in participants with unresectable or metastatic melanoma.

Conditions

Metastatic Melanoma; Unresectable Melanoma; Acral Melanoma; Mucosal Melanoma; Cutaneous Melanoma; Ocular Melanoma; Uveal Melanoma; Iris Melanoma; Conjunctival Melanoma; Non-Cutaneous Melanoma

Keywords

Melanoma

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants that Successfully Receive TBio-4101

  Percentage of participants who undergo tumor resection that successfully receive TBio-4101

  Day 7

Secondary Outcomes (6)

• Objective Response Rate (OOR)

  2 years after receiving TIL Transfer

• 6 Month Overall Survival (OS)

  at 6 Months

• 12 Month Overall Survival (OS)

  at 12 Months

• 6 Month Progression Free Survival (PFS)

  at 6 Months

• 12 Month Progression Free Survival (PFS)

  at 12 Months

Study Arms (1)

Infusion of TBio-4101 TIL

EXPERIMENTAL

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.

Biological: TBio-4101; Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Interleukin-2

Interventions

TBio-4101 BIOLOGICAL

TBio-4101 is a tumor-infiltrating lymphocyte (TIL) product that involves the use of special immune cells called T-cells. A T-cell is a type of lymphocyte, or white blood cell.

Also known as: Tumor-Infiltrating Lymphocyte

Infusion of TBio-4101 TIL

Cyclophosphamide DRUG

Participants will receive Cyclophosphamide 60 mg/kg/day intravenously (IV) in 250 mL over approximately 1 hour per day for 2 days.

Also known as: Cytoxan, Neosar

Infusion of TBio-4101 TIL

Fludarabine DRUG

Participants will receive an intravenously (IV) infusion of Fludarabine 25 mg/m2 for approximately 15 to 30 minutes for 5 days, prior to T-Cell infusion

Also known as: Fludara

Infusion of TBio-4101 TIL

Interleukin-2 DRUG

Participants will receive Interleukin-2 (IL-2) 600 000 IU/kg intravenously every 8 to 12 hours beginning within 24 hours after T-cell infusion.

Also known as: IL-2

Infusion of TBio-4101 TIL

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must have histologically confirmed, unresectable or metastatic melanoma as follows:
• Cutaneous, non-acral, melanoma (including melanoma of unknown primary)
• Cutaneous acral melanoma
• Mucosal melanoma
• Ocular melanoma (including uveal, iris, conjunctival melanoma)
• Participants must have failed, be refractory to, or unable to tolerate standard of care in the opinion of the Investigator. For participants with cutaneous non-acral melanoma, standard of care therapy includes a PD-1/L1 inhibitor, a CTLA-4 inhibitor, and if BRAF V600 activating mutation positive, a BRAF ± MEK inhibitor.
• Note: if treatment failure occurs during adjuvant therapy or within 6 months of adjuvant therapy completion, this will count as a failure of the applicable regimen as noted above.
• Any systemic therapy, including anti-cancer monoclonal antibodies, must have been completed at least 4 weeks from the start of lymphodepleting therapy (except for bridging therapy as defined below), and any prior therapy-related AEs must have resolved to Grade ≤ 1 except for alopecia and vitiligo. Neuropathy must have resolved to Grade ≤ 2.
• Participants must be between the ages of 18 and 75 years old. Additionally, participants who are ≥ 60 years of age must undergo a cardiology evaluation including a cardiac stress test after which they must be deemed to be low/acceptable risk.
• ECOG performance status of 0 or 1
• Participants must have adequate organ and marrow function as defined below:
• Absolute neutrophil count ≥ 1,500/mcL (non-growth factor supported)
• Platelet count ≥ 100,000/mcL
• Hemoglobin ≥ 8.0 g/dL
• AST (SGOT)/ALT (SGPT) ≤ 3 times the institutional ULN; ≤ 5 times ULN if patient has liver metastasis

You may not qualify if:

• Participants, regardless of age, who have a current or past medical history of ischemic heart disease, or clinically significant atrial or ventricular rhythm abnormality are excluded unless they undergo a cardiac stress test and cardiology clearance examination and are determined to be low or acceptable risk.
• Note: Participants with any clinically significant cardiac wall movement abnormality are excluded.
• Participants who have received prior cell therapy.
• Participants with either a primary immunodeficiency disorder (i.e., severe combined immunodeficiency syndrome) or acquired immunodeficiency disorders (such as HIV/AIDS)
• Pregnant women are excluded from this study because the agents used in this study have teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with TBio-4101 or the other agents in the study, breastfeeding should be discontinued if the mother is enrolled in the study.
• Participants taking systemic steroid therapy (other than replacement therapy) or therapy with any immunosuppressive medications such as mycophenolate mofetil (MMF). Participants who require dapsone for pneumocystis pneumonia (PCP) prophylaxis during TIL therapy are eligible.
• Participants who have a history of severe immediate hypersensitivity reaction to the study agents including cyclophosphamide, fludarabine, or aldesleukin/ IL-2 or any of their constituents
• Participants with a left ventricular ejection fraction (LVEF) ≤ 45% or New York Heart Association (NYHA) functional classification \> 1
• Forced expiratory volume (FEV1) ≤ 60% of predicted value and DLCO (corrected) \< 60% of predicted value
• Participants who, in the opinion of the Investigator, have a medical condition that would subject the patient to prohibitive risk by participation in this study, or who may be unable to safely complete the apheresis, tumor harvest, lymphodepletion regimen, TIL infusion, or aldesleukin/ IL-2 administration
• Participants with active infections requiring parenteral antibiotics
• Participants with autoimmune disease currently or within the past 6 months requiring systemic treatment with immunosuppressive doses of corticosteroids (\>10 mg of prednisone-equivalent daily dosing), immunosuppressive biologic agents, or disease modifying antirheumatic drug agents (DMARDs).
• Note: Participants with autoimmune thyroiditis on replacement thyroid medication are eligible.
• Participants requiring chronic anti-coagulant therapy that cannot either be discontinued or changed to an anti-coagulant such as a low molecular weight heparin, which has a relatively short half-life, if clinically indicated during the period of thrombocytopenia resulting from the lymphodepletion regimen
• Has evidence of impeding perforation, obstruction or bleeding (requiring transfusion) due to the tumor.

Sponsors & Collaborators

• H. Lee Moffitt Cancer Center and Research Institute: lead
• Turnstone Biologics, Corp.: collaborator

Study Sites (1)

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Related Links

• Moffitt Clinical Trial Search

MeSH Terms

Conditions

Melanoma; Uveal Melanoma

Interventions

Cyclophosphamide; fludarabine; fludarabine phosphate; Interleukin-2

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Uveal Neoplasms; Eye Neoplasms; Eye Diseases; Uveal Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Lymphokines; Proteins; Biological Factors

Study Officials

• Amod Sarnaik, MD

  Moffitt Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 14, 2022
• First Posted: November 29, 2022
• Study Start: November 22, 2022
• Primary Completion: December 3, 2024
• Study Completion: March 6, 2025
• Last Updated: April 2, 2026

Record last verified: 2026-03

Locations

US (1)