Genetically Modified T Cells for Solid Tumors

Recruiting in Palo Alto (17 mi)

Age: Any Age

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Waitlist Available

Sponsor: University Health Network, Toronto

No Placebo Group

Trial Summary

What is the purpose of this trial?

The target populations for this phase I study with TBI-1301 are patients with advanced solid tumors. Patients' tumors will be required to express NY-ESO-1, which include but is not limited to ovarian cancer, synovial sarcoma, esophageal cancer, lung cancer, bladder cancer, liver cancer, and malignant melanoma. Patients must be positive for HLA-A\*02:01 or HLA-A\*02:06 and the patient's tumor tissue must be positive for NY-ESO-1 antigen expression. The study will take the subject's T cells, which are a natural type of immune cell in the blood, and send them to a laboratory to be modified. The changed T cells used in this study will be the subject's own T cells that have been genetically changed with the aim of attacking and destroying cancer cells. The manufacturing of T cells takes about 1 month to complete. The T cells will be given back to the subject through an intravenous infusion. The purpose of this study is to test the safety of genetically changed T cells and find out what effects, if any, they have in subjects with advanced solid tumors. The purpose of this study is to evaluate the safety profile of TBI-1301, to determine the recommended phase 2 (RP2D) dose of TBI-1301 when administered following cyclophosphamide and fludarabine pre-treatment, to evaluate the safety of repeat dosing of TBI-1301, to assess the presence/absence of RCR appearance after TBI-1301 infusion, to assess the presence or absence of clonality by LAM-PCR, and to evaluate evidence of efficacy of TBI-1301 using RECIST v1.1.

Research Team

Eligibility Criteria

This trial is for adults with advanced solid tumors expressing NY-ESO-1, including lung, ovarian, and liver cancers. Participants must have a specific immune system marker (HLA-A*02:01 or HLA-A*02:06), an ECOG status of 0 or 1 indicating they are fully active or restricted in physically strenuous activity but ambulatory, measurable disease progression post-treatment, and adequate organ function. Pregnant women and those with autoimmune diseases, uncontrolled infections, recent immunosuppressants use (except certain steroids), HIV/HTLV/syphilis/hepatitis B/C infections are excluded.

Inclusion Criteria

Platelets ≥ 75x10^9/L (75,000/μl)

Total bilirubin ≤ 1.5 x upper limit of normal (ULN) (≤2.5X if Gilbert's disease)

AST(SGOT), ALT(SGPT) < 3.0 x ULN (< 5 x ULN with known liver metastases)

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Exclusion Criteria

Pregnant women are excluded.

I have or had Crohn's disease or ulcerative colitis.

You have a history of a weakened immune system from birth.

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Treatment Details

Interventions

TBI-1301 (CAR T-cell Therapy)

Trial OverviewThe study tests TBI-1301 therapy where patients' own T cells are genetically modified to target cancer cells expressing the NY-ESO-1 antigen. The safety of these engineered T cells will be evaluated along with their effect on tumor size using RECIST v1.1 criteria after pre-treatment with cyclophosphamide and fludarabine.

Participant Groups

2Treatment groups

Experimental Treatment

Group I: Cohort C (double infusion)Experimental Treatment3 Interventions

Cyclophosphamide will be given intravenously (by vein) at a fixed dose of 750mg/m\^2/d for 2 days. Fludarabine will be given intravenously at a fixed dose of 30mg/m\^2/d for 2 days. TBI-1301 cells will be infused on Day 0 and Day 14 at a dose of 5x10\^9 cells.

Group II: Cohort B (retreatment)Experimental Treatment3 Interventions