Abstract OT1-01-03: Adoptive cell transfer (ACT) using tumor infiltrating lymphocytes to target neoantigens in patients with metastatic breast cancer
Authors: Goff SL , Feldman SA , Somerville R , Rosenberg SA 
Published: May 2016

Abstract
Background: Adoptive transfer of tumor infiltrating lymphocytes (TIL) can cure patients with metastatic melanoma, likely based on the recognition of mutated neoantigens (Robbins et al Nature Medicine 2013). Although immunogenic cancer antigens have been found in gastrointestinal cancers (Tran et al Science 2014), this has not been widely studied in patients with breast cancer. The presence of TIL on pathologic examination of triple-negative breast cancers is a positive prognostic marker for disease-free survival and overall survival. This pilot study investigates the ability to grow TIL from breast cancer metastases, to identify personalized non-synonymous mutations and potential neoantigens, and to adoptively transfer TIL into patients with breast cancer.
Trial Design: This is a single-arm, non-randomized pilot study of adoptive immunotherapy in patients with metastatic epithelial cancers with a cohort designated for those patients with breast cancer. Once screened for eligibility, patients undergo metastectomy to obtain tissue for culture of TIL and extensive in vitro studies will be performed to identify TIL cultures reactive to neoantigens. Once robust TIL have been identified, the patient is admitted to the National Institutes of Health Clinical Center for conditioning chemotherapy, TIL infusion and interleukin-2. Treatment and recovery generally entails about three weeks as an inpatient.
Eligibility Criteria: Patients between the ages of 18 and 70 with metastatic breast cancer who have measurable metastatic disease with at least one lesion resectable with minimal morbidity. Patients must be refractory to standard systemic therapy and must have shown progression on at least two lines of chemotherapy prior to infusion of TIL. Patients must be of good performance status (ECOG 0-1) and have three or fewer brain metastases. In addition, patients must meet common hematologic and chemistry lab criteria. Given the nature of immunotherapy and the rigorous treatment, patients are ineligible for the following reasons: dependence on steroids, cardiac dysfunction, active infection, active major medical illness of the respiratory, cardiovascular or immune system.
Specific Aims: The aims are both clinical and research oriented. Of greatest interest is to determine the ability of autologous TIL to mediate tumor regression in patients with metastatic breast cancer. We will also be examining the phenotypic and functional characteristics of TIL derived from breast cancer metastases. We will be attempting to identify non-synonymous immunogenic mutations within resected tumors.
Statistical Methods and Trial Accrual: Twenty-one patients will be initially enrolled in the treatment phase of this cohort to assess toxicity and tumor responses. If two or more of the first 21 patients per groups shows a clinical response (PR or CR), accrual will continue to 41 patients, targeting a 20% goal for objective response. We have currently enrolled three patients on the screening phase of this trial and one patient on the treatment phase.
Contact Information: National Cancer Institute Surgery Branch Immunotherapy Referral Office, irc@nih.gov, (301) 451-1929, (866) 820-4505 Toll Free. ClinicalTrials.gov: NCT01174121.
Citation Format: Goff SL, Feldman SA, Somerville R, Rosenberg SA. Adoptive cell transfer (ACT) using tumor infiltrating lymphocytes to target neoantigens in patients with metastatic breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr OT1-01-03.