Efficacy and safety of nivolumab monotherapy in patients with high PD-1 positive CD8/Treg ratio in advanced NSCLC and GC: A phase II, multicenter study.

Background It is challenging to identify the appropriate patients who benefit from anti-PD-1/PD-L1 monotherapy. For predicting effectiveness of anti-PD-1/PD-L1 monotherapy, this open-label phase Ⅱ study (ONO-4538-88) evaluated the potential of the tumor infiltrating lymphocytes (TIL) biomarker: the balance between cytotoxic T cells and regulatory T cells. Methods Patients with advanced non-small cell lung cancer (NSCLC) or gastric cancer (GC) were screened between March 2021 and January 2022. Eligible patients who met the prespecified TIL biomarker criteria received nivolumab monotherapy. The primary endpoint was objective response rate (ORR). The secondary endpoints included overall survival (OS) and progression-free survival (PFS). Conventional biomarkers (tumor proportion score, combined positive score, tumor mutation burden, and microsatellite instability) were exploratorily analyzed, and safety was also assessed. Results Thirty-seven patients with NSCLC and 127 patients with GC were eligible for TIL analysis: 6 (16.2%) and 15 patients (11.8%) met the TIL biomarker criteria, respectively; a part of them were assessed. For NSCLC and GC, the ORR was 80.0% (4/5 patients) and 36.4% (4/11 patients), respectively; all the 5 patients and 5/11 patients had a reduction in tumor size, respectively; the median OS was not reached and 25.00 months, respectively; and the median PFS was not reached and 5.59 months, respectively. Treatment-related adverse events (TRAEs) occurred in 13/19 patients overall: 5/6 patients for NSCLC and 8/13 patients for GC. Conclusions Although the low positive rate of the TIL biomarker limits interpretation, the promising ORRs suggest the signs of the TIL biomarker's predictability for the nivolumab monotherapy.