This is a pilot study to evaluate feasibility, safety, and preliminary evidence of efficacy for intravenously administered, RNA electroporated autologous T cells expressing MET chimeric antigen receptors with tandem TCRζ and 4-1BB (TCRζ /4-1BB) co-stimulatory domains (referred to as "RNA CART-cMET") in patients with advanced melanoma or breast carcinoma.
This is a pilot study to evaluate feasibility, safety, and preliminary evidence of efficacy for intravenously administered, RNA electroporated autologous T cells expressing MET chimeric antigen receptors with tandem TCRζ and 4-1BB (TCRζ /4-1BB) co-stimulatory domains (referred to as "RNA CART-cMET") in patients with advanced melanoma or breast carcinoma. Subjects will be treated with IV administration of the RNA transduced anti-cMET CAR T cells for a total of up to six doses over a 2 week period. Each dose is 1x108 total T cells modified with RNA anti-cMET CAR. All subjects in both the melanoma and breast carcinoma arms will receive up to 6 doses of RNA CART-cMET cells, with no lymphodepleting chemotherapy administered prior to cell infusion Cell numbers are based on total cells with a portion of them having CAR expression depending on transduction efficiency and determined by flow cytometry Based on the product release criteria, at least 20% of the total cells will express the anti-cMET CAR. Treatment limiting toxicity (TLT). Adverse event reporting will begin at the start of the first dose of RNA CART-cMET and will continue until 4 months after the first infusion, or until another alternative therapy is initiated, whichever occurs earlier. Subjects will be continually reassessed for evidence of acute and cumulative toxicity.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
77
Intravenously administered, RNA electroporated autologous T cells expressing MET chimeric antigen receptors with tandem TCRζ and 4-1BB (TCRζ /4-1BB) co-stimulatory domains
University of Pennsylvania
Philadelphia, Pennsylvania, United States
Number of participants with treatment-related adverse events as assessed by CTCAE v4.03 in melanoma and breast cancer subjects
Time frame: from day 0 - month 4
Objective overall response rate by clinical exam for visible cutaneous tumors
Time frame: day 25 and month 4
Objective overall response rate by radiologic imaging using RECIST 1.1
Time frame: day 25 and month 4
Estimate the activity of RNA CART-cMET in subjects who receive at least 1 dose of cells by objective response rate using RECIST 1.1 criteria
Time frame: day -7 and day 11
Estimate the activity of RNA CART-cMET in subjects who receive at least 1 dose of cells by objective response rate using pathological evaluation of resected or biopsied tissue
Time frame: day -7 and day 11
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