Tumor Infiltrating Lymphocyte Therapy Combined With PD-1/LAG-3 Inhibition in Patients With Recurrent...

Area of Science:

• Oncology
• Immunotherapy
• Clinical Trials

Background:

• Ovarian cancer (OC) has lagged in benefiting from immuno-oncology advances.
• Tumor-infiltrating lymphocytes (TILs) show potential but require enhancement for lasting responses.
• High PD-1 and LAG-3 expression on OC TILs suggests immune checkpoint inhibitors (ICI) could be beneficial.

Purpose of the Study:

• To assess the safety and feasibility of TIL therapy combined with PD-1 and LAG-3 inhibitors in platinum-resistant recurrent OC.
• To evaluate immune monitoring and clinical efficacy as secondary endpoints.

Main Methods:

• A pilot study involving five patients with platinum-resistant recurrent OC.
• Treatment included TIL therapy and up to four cycles of combined PD-1/LAG-3 inhibitors.
• Patients had undifferentiated carcinoma, high-grade serous OC (HGSOC), or low-grade serous OC (LGSOC).

Main Results:

• The combined treatment was safe and feasible, with expected toxicity.
• A high rate of non-treatment-related complications was noted.
• Eighty percent (4/5) of patients experienced decreased tumor burden, including two unconfirmed partial responses.
• Differences in tumor burden, infusion product, and responses were observed between LGSOC and HGSOC.

Conclusions:

• TIL therapy combined with PD-1 and LAG-3 inhibition is safe and feasible for platinum-resistant OC.
• The study indicates potential clinical efficacy, warranting further investigation.
• Results are hypothesis-generating due to the small sample size, suggesting larger trials are needed.