Discussion
tumour, lymph node-only disease, UC
ADVANCED RENAL CELL CARCINOMA, SOLID TUMOUR, METASTASIS TO LYMPH NODE, TUMOUR, IMMUNE TOLERANCE
This study was an open-label, multicentre, non-randomised study to investigate the safety, tolerability, PK and preliminary anti-tumour activity of the anti-PD-L1 monoclonal antibody BGB-A333 alone and in combination with the anti-PD-1 monoclonal antibody tislelizumab in patients with advanced solid tumours. Treatment with BGB-A333 1350 mg Q3W, which was considered the RP2D, as monotherapy or in combination with tislelizumab 200 mg Q3W, was generally well tolerated with a manageable safety profile.The safety profile of BGB-A333 in the Phase 1a study was consistent with the established profile of anti-PD-1/L1 therapies [The present study also provided preliminary evidence of the anti-tumour activity of BGB-A333 in combination with tislelizumab in PD-1/PD-L1 inhibitor naïve patients with advanced solid tumours, most of whom had received at least one prior line of systemic therapy. In the combination dose-expansion phase (Phase 2) in patients with UC, the confirmed ORR was 41.7% (5/12 patients), with four patients achieving CR and one patient achieving PR, and responses were durable. These preliminary data on the anti-tumour activity of this combination in patients with advanced UC are more encouraging than those reported with MEDI0680 plus durvalumab in patients with previously treated, immunotherapy-naïve, advanced renal cell carcinoma, which resulted in an ORR of only 16.7% [All patients in the combination dose-expansion phase had UC. Our preliminary results on the anti-tumour activity of BGB-A333 plus tislelizumab combination therapy are encouraging in light of the continued unmet need for patients with advanced UC ineligible for first-line platinum-based chemotherapy, and for those requiring later lines of therapy [In the present study, most responses in the combined dose-expansion Phase 2 part were seen in UC patients with lymph node-only disease. Metastasis to lymph nodes is a key step in the development of tumour cell immune tolerance [The exposures of BGB-A333 (AUC