GT101 autologous TIL therapy in patients with recurrent and metastatic cervical cancer: A phase 1 study.

Abstract

5532 Background: Adoptive cell therapy with autologous TILs has shown durable clinical benefit in selected advanced solid tumors after progression on standard therapies. We report results from a phase I, open-label, single-arm, multicenter trial (NCT05430373) evaluating GT101 in patients with recurrent or metastatic cervical cancer. Primary objectives were safety; second objectives included preliminary efficacy and PK. Methods: Eleven patients with recurrent or metastatic cervical cancer received a lymphodepletion regimen followed by GT101 infusion and high-dose IL-2. The primary endpoint was safety, including treatment-emergent adverse events (TEAEs), serious adverse events (SAEs) and adverse events (AEs), graded per CTCAE v5.0. Secondary endpoints included objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), duration of response (DoR), and overall survival (OS), assessed by RECIST v1.1. Flow cytometry of immune cells and T cell receptor (TCR) sequencing were performed on peripheral blood samples collected from patients before and after treatment. Results: As of September, 2025, 11 patients were treated (median age was 48 years; median two prior lines of therapy). Following FC lymphodepletion, patients received GT101 at doses ≥5×10⁹ viable cells (median 4.1×10¹⁰), followed by high-dose IL-2 (600,000 IU/kg, up to 6 doses). Most AEs were Grade 1-2. Grade ≥3 AEs were primarily related to lymphodepletion and IL-2, and included lymphopenia, leukopenia, neutropenia, anemia, pyrexia, and thrombocytopenia; most resolved or improved to Grade ≤2 within 14 days. The ORR was 45.5% (5/11), with DCR of 90.9% (10/11). Median DoR was 6.4 month. Four patients (36.4%) achieved confirmed PR, one patient (9.1%) achieved a CR, and five patients (45.5%) had stable disease (SD). Median PFS was 4.83 months; OS follow-up is ongoing. One patient with stage IIIC2 cervical squamous cell carcinoma achieved a confirmed CR lasting 14.5 months, with tumor burden reduced from a baseline sum of diameters of 71.57 mm to complete resolution by Week 12. Pharmacokinetics and Correlation Analyses: Peripheral blood analyses demonstrated peak circulating T cells 5-7 days post-infusion, followed by contraction to near-baseline by two weeks. Responders exhibited lower proportions of CD39 + PD-1 + T cells. TIL infusion increased T-cell clonal diversity in all patients, with greater expansion observed in non-responders who has lower baseline diversity; persistence of TIL-derived clones did not differ consistently between groups. Conclusions: GT101 demonstrated a manageable safety profile with no treatment-related SAEs or dose-limiting toxicities and showed clinically meaningful and durable antitumor activity in recurrent or metastatic cervical cancer. These findings support further clinical development, and a pivotal phase II study is ongoing. Clinical trial information: NCT05430373 .