Abstract
Purpose: 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 lymphocyte (TIL) biomarker: the balance between cytotoxic T cells and regulatory T cells. Patients and methods: Patients with advanced non-small cell lung cancer (NSCLC) or gastric cancer 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 and progression-free survival. 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 gastric cancer 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 gastric cancer, the ORR was 80% (4/5 patients) and 36.4% (4/11 patients), respectively; all the five patients and 5/11 patients had a reduction in tumor size, respectively; the median overall survival was not reached and 25 months, respectively; and the median progression-free survival was not reached and 5.59 months, respectively. Treatment-related adverse events occurred in 13/19 patients overall: 5/6 patients for NSCLC and 8/13 patients for gastric cancer. Conclusions: Although the low positive rate of the TIL biomarker limits interpretation, the promising ORRs suggest signs of the TIL biomarker's predictability for nivolumab monotherapy. Significance: In this phase II study, we examined the predictive utility of the TIL biomarker for nivolumab monotherapy. Although the positivity of the TIL biomarker was limited, the promising efficacy and safety profile in the TIL biomarker-positive patients may suggest the potential utility of the TIL biomarker.