Treatment with tumor-infiltrating lymphocytes is associated with improved progression-free survival (PFS) vs ipilimumab for patients with unresectable advanced melanoma, according to findings from a phase a phase 3 trial.

These results were presented at the 2022 European Society of Medical Oncology (ESMO) Congress by John Haanen, MD, Netherlands Cancer Institute, Amsterdam.

“Immune checkpoint inhibitors and targeted therapies have greatly improved the outcome of patients with advanced melanoma. However, as approximately half will not derive durable benefit, a large unmet need for additional treatment options remains,” explained Dr Haanen and colleagues.

This led investigators to study adoptive cell therapy with tumor-infiltrating lymphocytes in this patient population, showing great promise in phase 1/2 trials. The presentation at the ESMO Congress reported the first data from a phase 3 trial exploring the role of tumor-infiltrating lymphocytes in this space.

The multicenter, open label phase 2 trial enrolled 168 patients aged 18 to 75 years with unresectable stage IIIC-IV melanoma; 86% of patients were refractory to anti-PD1 therapy. Patients were randomized in a 1:1 ratio to receive tumor-infiltrating lymphocytes (n = 84) or ipilimumab (n = 84) and stratified based on BRAF^V600 mutation status, treatment line, and treatment center.

The primary end point of the study was PFS. Secondary end points included overall response rate, complete response rate, overall survival (OS), and safety.

With a median follow-up of 33 months, median PFS was 7.2 months (95% confidence interval [CI], 4.2 to 13.1) for tumor-infiltrating lymphocytes vs 3.1 months (95% CI, 3.0 to 4.3) for ipilimumab (hazard ratio [HR], 0.50; 95% CI, 0.35 to 0.72; P <.001). The overall response rates were 49% (95% CI, 38% to 60%) for tumor-infiltrating lymphocytes and 21% (95% CI, 13% to 32%) for ipilimumab with 20% (95% CI, 12% to 30%) and 7% (95% CI, 3% to 15%) of patients experiencing complete responses, respectively.

In addition, the median OS was 25.8 months (95% CI, 18.2 to not reached) and 18.9 months (95% CI, 13.8 to 32.6) for ipilimumab (HR, 0.83; 95% CI, 0.54 to 1.27; P = .39). All patients who received tumor-infiltrating lymphocytes experienced grade ≥3 adverse events vs 57% who received ipilimumab.

“[Tumor-infiltrating lymphocyte] therapy significantly improved PFS compared to ipilimumab in patients with advanced melanoma, the vast majority being anti-PD1 refractory, making it a possible new treatment option in this patient population,” concluded Dr Haanen and colleagues.

Source:

Haanen J, Rohaan M, Borch TH, et al. Treatment with tumor-infiltrating lymphocytes (TIL) versus ipilimumab for advanced melanoma: Results from a multicenter, randomized phase III trial. Presented at: ESMO Congress; September 9-13, 2022. Paris, France and virtual. Abstract LBA3.