T Cell Receptor Immunotherapy for Patients With Metastatic Non-Small Cell Lung Cancer

Description

Background:

* Patients with metastatic non-small cell lung cancer (NSCLC) have few approved therapeutic options and those that exist are of transient benefit.
* Recent clinical experiences with experimental agents that release checkpoints on the host immune response (such as anti-PD-1 and anti-PDL1 antibody) have induced tumor regressions in patients with NSCLC.
* Data from sequencing the genomes of human cancers have shown that, like malignant melanoma, NSCLC has a very high rate of tumor-specific genomic mutation.
* In metastatic melanoma, a tumor infiltrating lymphocyte cell therapy product (TIL) can mediate the regression of bulky disease at any site when administered to an autologous patient with high dose aldesleukin following a non-myeloablative but lymphodepleting chemotherapy preparative regimen.
* Recent studies on tumor infiltrating lymphocytes from melanoma have demonstrated that they can frequently recognize tumor-specific mutated proteins as “foreign” antigens and that is one hypothesis as to why melanoma is such an immunogenic tumor.
* We propose to investigate the feasibility, safety, and efficacy of growing and administering an autologous tumor infiltrating lymphocyte product (TIL) to patients with metastatic NSCLC

Objectives:

Primary objective:

-To determine the rate of tumor regression in patients with advanced non-small cell lung cancer (NSCLC) who receive an autologous tumor infiltrating lymphocyte product (TIL) plus aldesleukin following a lymphodepleting preparative regimen.

Eligibility:

* Patients who are >= 18 years of age and <= 72 years of age must have:

* Advanced NSCLC refractory to standard therapy
* A site of tumor that can be excised with minimal morbidity and mortality or that requires excision for clinical indications
* At least one remaining site of measurable disease
* Normal basic laboratory values.
* Patients may not have:

* Concurrent major medical illnesses that preclude aldesleukin administration or immunosuppression;
* Severe hepatic function impairment due to liver metastatic burden;
* Any form of immunodeficiency;
* Severe hypersensitivity to any of the agents used in this study;
* Symptomatic brain metastases or more than 3 CNS metastases

Design:

* Patients will undergo biopsy or resection to obtain tumor for generation of autologous tumor infiltrating lymphocyte cultures and autologous cancer cell lines.
* The TIL product will be generated according to current TIL-lab standard operating procedures, using interleukin-2 and OKT3 antibody.
* All patients will receive a non-myeloablative lymphocyte depleting preparative regimen of cyclophosphamide and fludarabine
* Cohort 1 will receive TIL on day 0 and then begin high-dose aldesleukin (720,000 IU/kg IV); cohort 2 will receive TIL on day 0 and then begin low-dose aldesleukin (72,000 IU/kg IV). Assignment to this cohort will be made if there are concomitant medical conditions that would preclude the use of high-dose aldesleukin
* Clinical and immunologic response will be evaluated about 4-6 weeks after TIL infusion.
* For both cohorts 1 and 2, using a Phase II design, 21 patients will be initially enrolled in each group to assess toxicity and tumor responses. If two or more of the first 21 patients per group show a clinical response (PR or CR), accrual will continue to 41 patients, targeting a 20% goal for objective response. In order to allow for a small number of non evaluable patients, a total of 85 patients may be enrolled over 5 years.