Phase I/II Study of Autologous T Cells to Express T-Cell Receptors (TCRs) in Subjects With Solid Tumors

Inclusion Criteria

• Patients who have completed the HLA Typing and Tumor Neoantigen Identification Protocol (TCR001-002) and for whom a TCR(s) matching the subject's somatic mutation(s) and HLA type restriction combination is available in Alaunos' Clinical TCR library
• Patients who have previously received at least one line of standard systemic therapy for their advanced/metastatic cancer and have either progressed, recurred, or were intolerant to the previous treatment. Specifically:
• Subgroup 1. Gynecologic cancers (i.e., ovarian or endometrial):
• Ovarian cancer
• Endometrial cancer
• Subgroup 2. Colorectal cancer
• Subgroup 3. Pancreatic cancer
• Subgroup 4. Non-small cell lung cancer (NSCLC)
• Subgroup 5. Cholangiocarcinoma
• Patients must have evaluable or measurable disease per RECIST 1.1 with at least one lesion that can be measured that is not the biopsied lesion.
• Patients must be able to provide written informed consent.
• Patients must be age ≥ 18 years.
• Clinical Performance Status of ECOG 0 or 1. Approval from the Alaunos Medical Monitor is required for ECOG of 2.
• Patient must be willing and able to provide written informed consent for the long-term follow-up protocol (TCR001-202) for up to 15 years post TCR-T Cell drug product infusion per FDA requirements.
• Adequate bone marrow reserves as assessed by the following hematology laboratory criteria:
• Adequate major organ system function
• A washout period must have elapsed since completion of any prior systemic therapy, and apheresis with guidelines as follows (windows other than what is listed below should be allowed only after consultation with the Medical Monitor); subjects' non-hematologic toxicities from any prior systemic therapy must have recovered to ≤ Grade 1 (with the exception of neuropathy and alopecia) or baseline prior to starting the protocol's therapy.
• Patients may have undergone minor surgical procedures or limited-field radiotherapy provided any major organ toxicities have recovered to ≤ Grade 1.
• Female patients must not be pregnant or breastfeeding.

Exclusion Criteria

• Patients with known active CNS metastases
• Concurrent systemic steroid therapy
• Any form of primary immunodeficiency
• Patients who have decreased immune competence
• History of severe immediate hypersensitivity reaction to cyclophosphamide, fludarabine, aldesleukin or bendamustine
• Severe chronic respiratory condition
• History of a bleeding disorder or unexplained major bleeding diathesis
• Arm B Criteria only: Clinically significant patient history which in the judgment of the principal investigator (PI) would compromise the subject's ability to tolerate high-dose aldesleukin;
• Any major bronchial occlusion or bleeding not amenable to palliation.
• Patients with psychiatric illness/social situations at the time of treatment that would limit compliance with study requirements.
• Participants with known active, uncontrolled bacterial, fungal, or viral infection
• Patients with a prior history or concurrent malignancy
• Active unstable or clinically significant medical condition
• History of any major cardiovascular conditions within the past 6 months