a study of tbio-4101 (til) and pembrolizumab in patients with advanced solid tumors

Conditions: Breast Cancer; Colorectal Cancer; Uveal Melanoma; Cutaneous Melanoma; Non-Small Cell Lung Cancer; Head and Neck Squamous Cell Carcinoma

Summary: 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.

Eligibility criteria:
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

Keywords: mss-crc til tumor infiltrating lymphocyte tnbc hr+ breast er+ breast msi-crc personalized medicine ocular melanoma