Assessing the safety and efficacy of GT201: A first-in-class autologous tumor-infiltrating lymphocyte monotherapy in advanced solid tumors.

6038 Background: For patients with unresectable recurrent or metastatic solid tumors that progress after chemotherapy, immune checkpoint inhibitors (ICIs), or targeted therapy, treatment options are limited. GT201, featuring membrane-bound IL-15 (mbIL-15) expressed on TILs, aims to enhance immune activation in the tumor microenvironment and may demonstrate efficacy and durable responses in these advanced cases. We present data from nine patients enrolled in open-label, single-arm studies to investigate the safety and efficacy trends of GT201 therapy. Methods: The GT201 study's primary endpoint was to assess TEAEs, including SAEs and AEs, using the CTCAE version 5.0 grading scale. The secondary endpoint focused on preliminary efficacy parameters, including ORR, DCR, PFS, DOR, OS following RECIST v1.1 guidelines. Results: As of January 15, 2025, nine patients have been enrolled in the study, with a median age of 52 years and a median of two prior therapy lines. Among them, one patient had bone metastases, two had liver metastases, and one had brain metastases. After standard FC lymphodepletion, patients received GT201 infusions at doses of ≥5×10⁹ viable cells. Seven patients subsequently received IL-2 post-infusion. Most adverse events (AEs) were Grade 1 or 2. Grade ≥3 AEs, related to lymphodepleting chemotherapy and IL-2, included decreased lymphocyte, neutrophil, and white blood cell counts, pyrexia, and tachycardia. All Grade ≥3 AEs resolved or downgraded to Grade ≤2 within 14 days. Among the nine response-evaluable patients with various cancers, including head and neck squamous cell carcinoma (HNSCC), non-small-cell lung cancer (NSCLC), melanoma, cervical cancer, and ovarian cancer, the objective ORR was 55.6% (5/9), and the disease control rate (DCR) was 77.8% (7/9). One patient (11.1%) achieved complete response (CR), four (44.4%) had partial responses (PR), and two (22.2%) had stable disease (SD) as their best response. Notably, in the HNSCC subgroup, both patients achieved objective responses (CR and PR) (2/2, 100%). In the NSCLC subgroup, all three patients achieved disease control (SD ≥24 weeks or PR) (3/3, 100%). GT201 cells were detected in all patients, indicated by IL15RA protein staining on peripheral T cells and transgene copy number in peripheral white blood cells. GT201 cells expanded robustly and persisted in peripheral blood for at least six months post-infusion. Conclusions: In patients with heavily pretreated advanced or metastatic solid tumors, GT201, infused after FC lymphodepleting chemotherapy and high-dose IL-2, exhibited a manageable safety profile. GT201 demonstrated a favorable clinical profile in HNSCC, with an encouraging objective response rate and durable responses. No Grade ≥3 adverse events related to GT201 treatment were observed, supporting its potential as a treatment option worth further exploration. Clinical trial information: NCT05729399 , NCT06190275 .