Clinical Trial 22284

Study Title

A Phase lb Study of TBio-4101 (Autologous Selected and Expanded Tumor-Infiltrating Lymphocytes [TIL]) and Pembrolizumab in Patients with Advanced Solid Tumor Malignancies (STARLING)

Summary

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. Pembrolizumab is provided after the resolution of IL-2 toxicities. The trial is open to solid tumors of varying tumor mutational burdens.

Objective

Primary Objective: Define the safety and tolerability of NMA-LD chemotherapy, TBio-4101, aldesleukin (IL-2), and pembrolizumab Secondary objectives: -Determine ORR in all patients and within each treatment cohort RECIST 1.1 and iRECIST by an independent central imaging assessment -Evaluate DoR and DCR in all patients and within each treatment cohort using RECIST 1.1 and iRECIST by an independent central imaging assessment -Assess the feasibility of TBio-4101 in enrolled patients across indications (cumulative and by indication) Exploratory Objectives: -Evaluate TTB and PFS in all patients using RECIST 1.1 and iRECIST -Evaluate OS -Explore potential significance of T cell phenotype including TCR clonality and diversity and tumor antigen reactivity of TBio-4101 as they correlate with clinical outcome -Evaluate TBio-4101 engraftment, persistence, activation, phenotype, transcriptome profile and tumor infiltration and correlate these findings with clinical outcome -Compare baseline and on treatment determinants in the tumor by pathology and genomic analysis of pre- and on-treatment biopsies with clinical response -Assess post-PD anti-cancer therapy with responses and OS