334 Phase 1 trial of GC101, an IL2free autologous tumor-infiltrating lymphocyte (TIL) therapy, in recurrent high-grade glioma: safety and preliminary efficacy
Year: 2026
Type: conference-abstract
Abstract: Background Given the poor prognosis of recurrent high-grade glioma (HGG) and the unexplored potential of TIL therapy in this disease, we developed a modified IL-2-free TIL therapy (GC101) with lowintensity preconditioning, which overcomes the high safety risks associated with conventional TIL therapy, and conducted a phase 1 trial to evaluate the safety and preliminary antitumor activity of autologous TILs derived from primary surgical specimens in patients with recurrent HGG.Methods This single-center, open-label, nonrandomized phase 1 trial ( NCT04943913) enrolled patients with recurrent HGG who had failed standard therapies. Tumor tissues were obtained from initial resection specimens. After ex vivo expansion in a GMP facility, patients received a lymphodepleting preconditioning regimen consisting of either cyclophosphamide (300 mg/m2/day, on days –5 to –3) plus hydroxychloroquine (600 mg on day –1), or temozolomide (200 mg/day, on days –5 to –3) plus hydroxychloroquine (600 mg on day –1). This was followed by a low-dose anti-PD-1 antibody (sintilimab, 100 mg) and single intravenous TIL infusion on day 0. The study endpoints were safety and objective response rate (ORR) per RANO 2.0.Results As of March 12, 2026, four patients (3 male, 1 female; median age 53 years) were treated, including one with WHO grade 3 oligodendroglioma and three with WHO grade 4 glioblastoma. Before TIL infusion, all patients had received at least 2 regimens, with a maximum of 4 regimens. Prior to TIL infusion, all patients had received surgery, radiotherapy, and systemic chemotherapy. TIL products were successfully expanded from surgical tissues (mean yield 2.55 × 10 1° cells). No dose-limiting toxicities or serious adverse events were observed. All patients experienced treatment-emergent adverse events (AEs), mostly grade 1–2. One grade 3 lymphopenia occurred and resolved rapidly. Among four patients, best responses were: complete response (CR, n = 1), partial response (PR, n = 1), stable disease (SD, n = 1), and progressive disease (PD, n = 1). The ORR was 50% (95% CI: 6.76%–93.24%) and disease control rate (DCR) was 75% (95% CI: 19.41%–99.37%), with objective responses achieved in patients with WHO grade 3 or 4 HGGs, including a CR in grade 4. Median progression-free survival was 9.4 months (range 0.6–25.4 months) with a median followup of 10.9 months.Conclusions GC101 TIL therapy derived from early surgical specimens is feasible and shows a manageable safety profile with promising antitumor activity in recurrent glioblastoma. These data support further clinical development of GC101 TILs in primary brain tumors.
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,490
OpenAlex ID: W7225177400