A Study of TBio-4101 (TIL) and Pembrolizumab in Patients With Advanced Solid Tumors

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.

• TBio-4101 (Biological), also known as TIL, autologous, tumor-reactive, T-cell product: TBio-4101 is an autologous selected and expanded tumor infiltrating lymphocyte (TIL) product generated following ex vivo expansion of tumor reactive TIL population found in tumor harvest. After preparation with non-myeloablative lymphodepletion chemotherapy (cyclophosphamide and fludarabine) followed by low dose radiation,TBio-4101, and IL-2.
• Pembrolizumab (Drug), also known as Keytruda: Pembrolizumab will be administered after TIL infusion and continue every 3-6 weeks for up to 2 years.

Primary outcomes

• Safety and tolerability [25 months]: The incidence of treatment-emergent adverse events will be tabulated using NCI CTCAE v5.0

Secondary outcomes

• Proportion of patients with a response (ORR) [25 months]: Percentage of all patients and within each cancer indication with a CR or PR as assessed by the independent central radiologist using RECIST 1.1 and iRECIST
• Estimated Disease Control Rate (DCR) [25 months]: Portion of patient whose best response is a CR, PR, or stable disease (SD) as assessed by the independent central radiologist using RECIST v1.1 and iRECIST
• Estimated Duration of Response (DoR) [25 months]: Duration of response, as measured in weeks, that patients with a CR or PR have no progressed (PD), as assessed by the independent central radiologist using RECIST v1.1 and iRECIST,

Sex: All, ages: 18 Years to 70 Years

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

• Ines Verdon, MD, Study director, Turnstone Biologics, Corp.