Sponsor decision

A multicenter trial to investigate TBio-4101, an autologous, neoantigen-selected, tumor-reactive TIL product, in patients with advanced solid malignancies.

This is a Phase 1 study to investigate TBio-4101. TBio-4101 is an autologous tumor infiltrating lymphocyte (TIL) therapy that utilizes tumor specific antigens to select, sort, and expand patient-specific tumor-reactive T-cells to be reinfused into the patient. The adoptive cell therapy is further enhanced through the use of non-myeloablative chemotherapy prior to TIL infusion, followed by the TIL plus IL-2 infusion. Low-dose radiation therapy is administered prior to and after TIL plus IL-2 infusion. Pembrolizumab is provided after the resolution of IL-2 toxicities. The trial is open to solid tumors of varying tumor mutational burdens.

Key Inclusion Criteria:

• Advanced or metastatic breast carcinoma, colorectal adenocarcinoma, uveal melanoma, cutaneous melanoma, non-small cell lung cancer, or head and neck squamous cell carcinoma that has failed or is refractory to standard of care therapy
• Have at least one target lesion that can be used for response assessments and have at least 1 tumor amenable for tissue harvest for TIL manufacturing.
• ECOG performance status of 0 or 1
• Demonstrate adequate organ function
• Additional inclusion criteria exist

Key Exclusion Criteria:

• Known additional malignancy that is progressing or has required active treatment within the past 3 years
• Diagnosis of immunodeficiency or receiving chronic systemic steroid therapy or any other form of immunosuppressive
• Currently infected with HIV Type 1 and Type 2, hepatitis B virus (HBV), hepatitis C virus (HCV), treponema pallidum (e.g., syphilis), West Nile virus (WNV), Human T-lymphotropic virus types 1 or II (HTLV I/II), or cytomegalovirus (CMV)
• Known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Patients with previously treated brain metastases may participate provided they are radiologically stable
• Serious cardiac condition, such as uncontrolled hypertension, concurrent congestive heart failure, prior history of Class III/IV cardiac disease (New York Heart Association [NYHA]), history of cardiac ischemia within the past 6 months, or prior history of cardiac arrhythmia requiring treatment. Patients who are > 60 years of age must undergo cardiology clearance exam and cardiac stress test.
• Prior cell therapy or organ transplant
• History of severe immediate hypersensitivity reaction to cyclophosphamide, fludarabine, IL-2, or pembrolizumab, or any of their constituents
• LVEF ≤ 45%
• FEV1 ≤ 60% of predicted value and DLCO (corrected) < 60% of predicted value
• Chronic anti-coagulant therapy that cannot either be discontinued or temporarily changed
• Additional exclusion criteria exist