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

5533 Background: GT101 is Grit’s tumor-infiltrating lymphocyte (TIL) product. Adoptive cell therapy using autologous TILs has shown efficacy and long-term responses in patients with certain advanced solid tumors that have progressed after conventional therapies. We present data from 11 patients with recurrent or metastatic cervical cancer enrolled in a Phase 1, open-label, single-arm, multicenter trial (NCT05430373) of GT101. The study aims to investigate the safety profile, efficacy trends, and duration of response. Methods: Eleven patients with recurrent or metastatic cervical cancer were enrolled in the study, receiving a lymphodepletion regimen followed by GT101 infusion and IL-2 administration. The study's primary endpoints were treatment-emergent adverse events (TEAEs), including serious adverse events (SAEs) and adverse events (AEs), assessed using the CTCAE version 5.0 grading scale. Secondary endpoints included objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), duration of response (DoR), and overall survival (OS) based on RECIST version 1.1. Results: As of August 1, 2024, 11 patients received treatment, with a median age of 48 years and two prior therapy lines. Following FC lymphodepleting chemotherapy, patients received GT101 infusion at doses of ≥5×10⁹ viable cells, with a median dose of 4.1×10¹⁰ viable cells, followed by high-dose IL-2 (600,000 IU/kg, up to 6 doses). Most adverse events (AEs) were Grade 1 or 2. Grade ≥3 AEs, primarily related to lymphodepleting chemotherapy and IL-2, included decreased lymphocyte, white blood cell, and neutrophil counts, anemia, pyrexia, and decreased platelet count. Most Grade ≥3 AEs resolved or downgraded to Grade ≤2 within 14 days. Among 11 cervical cancer patients, the objective ORR was 45.5% (5/11), with disease control in 10/11 patients (90.9%). Four patients (36.4%) had confirmed PR, one (9.1%) achieved CR, and five (45.5%) had SD; one patient had unconfirmed PD. The median PFS was 4.83 months, and median OS has not yet been reached. A patient with CR maintained this response for 14.5 months, diagnosed with stage IIIC2 cervical squamous cell carcinoma, and underwent surgical resection of metastatic lymph nodes. The SOD at baseline was 71.57 mm, reduced to 29.12 mm after 28 days. At week 12 post-GT101 treatment, imaging showed complete response of the lesion, achieving CR. Conclusions: In the GT101 Phase 1 study, no treatment-related SAEs or DLTs were observed. GT101, infused after FC lymphodepleting chemotherapy and high-dose IL-2, exhibited a manageable safety profile. It demonstrated clinically meaningful activity and durable responses in patients with recurrent and metastatic cervical cancer. These promising results indicate favorable long-term survival outcomes, durable responses, and no long-term safety concerns related to GT101. Clinical trial information: NCT05430373 .