A Phase 2 Study of Autologous Tumor Infiltrating Lymphocytes (LN-145) in Patients With Pretreated Metastatic Triple Negative Breast Cancer

• Ability to understand the requirements of the study. Specifically, the patient has to provide written informed consent (as evidenced by signature on an ICF approved by the Yale Human Investigation Committee (HIC).

• All patients must have a triple negative metastatic breast cancer (Estrogen Receptor negative, Progesterone Receptor negative, HER2 negative) as defined by the 2018 ASCO CAP guidelines.

• Patients must have a confirmed diagnosis of metastatic triple negative breast cancer (Stage IV) histologically confirmed as per American Joint Committee on Cancer \[AJCC\] staging system).

• Patients must have had at least one and no more than three prior lines of systemic anticancer therapies for metastatic disease.

• Patients must have disease progression from the last line of therapy.

• Patients must have at least one resectable lesion of a minimum 1.5 cm in diameter (or aggregate of 1.5 cm if multiple lesions are sampled) post-resection for TIL investigational product production.

• Patients must have remaining measurable disease as defined by RECIST 1.1 following tumor resection for TIL manufacturing

• Patients must be ≥ 18 years of age at the time of consent.

• Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and an estimated life expectancy of ≥ 3 months in the opinion of the Investigator.

• Female patients of childbearing potential or female partners of childbearing potential of male participants, must be willing to practice an approved method of birth control during treatment and for 12 months after receiving all protocol-related therapy.

• Patients must have the following hematologic parameters:

‣ Absolute neutrophil count (ANC) ≥ 1000/mm3;

⁃ Hemoglobin ≥ 9.0 g/dL;

⁃ Platelet count ≥ 100,000/mm3

• Patients must have adequate organ function.

• Patients must be seronegative for the human immunodeficiency virus (HIV1 and HIV2).

• Patients must have a washout period of 21 days from last anticancer therapy prior to the first study treatment (ie, start of NMA LD).

• Palliative radiation therapy: prior external beam radiation is allowed provided all radiation-related toxicities are resolved to Grade 1 or baseline;

‣ The tumor lesion(s) being assessed as target for response via RECIST 1.1 must be outside of the radiation portal (however, if within the portal, they must have demonstrated progression);

⁃ Surgery/pre-planned procedure: previous surgical procedure(s) is permitted provided that wound healing has occurred, all complications have resolved, and at least 14 days have elapsed (for major operative procedures) prior to the tumor resection.

• Patients must have recovered from all prior anticancer treatment-related adverse events (TRAEs) to Grade ≤ 1 (per Common Terminology Criteria for Adverse Events \[CTCAE\], version 5.0).

• Patients must have provided written authorization for use and disclosure of protected health information.

• Must be able and willing to comply with the study visit schedule and protocol requirements including long-term follow-up (LTFU).