Harnessing the power of tumor-infiltrating lymphocytes: A first-in-human study of GT201 as monotherapy in advanced solid tumors.
Authors: Liu Yarong , Fang Weijia , Han Zhengxiang , Chen Kai , Chen Youguo , Yu Jing , Liu Yishen , Ma Liqing , Shi Zixiao , Sun Jingwei , Cui Jun , Wang Pin 
Published: June 2023

2551 Background: Genetically engineered TIL has shown features such as prolonged memory that can improve therapeutic efficacy in tumor mouse models. GT201 is an engineered TIL that expresses a membrane-bound IL-15 (mbIL-15), and preclinical studies have demonstrated enhanced antitumor reactivity. A phase 1 study was initiated to evaluate the preliminary safety of GT201 and to identify Optimal Biological Dose (OBD) suitable for monotherapy expansion. Methods: The dose-escalation study (using TITE-BOIN design) intended to enroll patients (pts) with advanced treatment-refractory solid tumors. Once the OBD is identified, a monotherapy expansion phase will be opened for patients with various solid tumors. Enrolled patients were preconditioned with a nonmyeloablative (NMA) lymphodepletion regimen and treated by autologous infusion of the GMP-grade G201 cell product, followed with supportive low dose IL-2 administration. Results: As of January 17, 2023, the dose-escalation study enrolled 4 pts, all of whom were female with a median age of 52.6 years. The median number of infused TIL cells was 5.3E+09. All pts experienced TRAEs, with the majority being grade 1 or 2. The most common grade 3/4 TRAEs were lymphopenia (100%), leukopenia (25%) and neutropenia (25%), which were related to the NMA regimen. No dose-limiting toxicities (DLTs) or TIL-related grade ≥3 TRAEs were observed. Median time on study was 17 wks (6–30 wks). One pt with highly treatment-refractory cervical cancer experienced a confirmed partial response (PR) after 16 wks that was durable for 30 wks (RECIST 1.1). Two pts (cervical cancer and melanoma) experienced disease stabilization, while another malignant melanoma pt experienced progressive disease. Despite varying doses of TILs (5.0E+09 to 1.40E+10) and IL-2 (up to 3.0E+05 IU/kg), all patients receiving GT201 therapy showed robust T cell expansion post-infusion, with higher doses of IL-2 leading to more rapid TIL expansion. GT201 TILs could be detected in patients after one month post-infusion, indicating promising activation and long-term persistence of the infused TILs. Based on safety, tolerability, PKs, and preliminary efficacy, a TIL dose of 1.0E+10 and an IL-2 dose of 3.0E+05IU/kg was selected as the OBD for the study. Conclusions: The results of the first-in-human study of GT201, a mIL-15 expressed on TILs, demonstrate promising preliminary findings as a monotherapy in pts with advanced cancers. The administration of GT201 was associated with robust T cell expansion, as well as prolonged persistence of infused TILs. Results of mbIL-15 expressed TIL demonstrates that GT201 has good tolerability with encouraging preliminary antitumor activity as a monotherapy. Further investigations, including correlative biomarker analyses and updated safety and clinical outcome data, will be presented at the meeting. Clinical trial information: NCT05430360 .