Discussion
DLTs, pembrolizumab, toxicities, disease shrinkage, gastroesophageal adenocarcinoma, deaths
METASTATIC UROTHELIAL CARCINOMA, DISEASE, GASTRIC CANCER
We designed this single-arm Phase I trial to understand the safety and tolerability of treatment with rivoceranib in combination with the FDA-approved anti-PD1 antibody pembrolizumab. Rivoceranib increases antitumor immunity when combined with the non-FDA approved anti-PD1 antibody camrelizumab in several contexts [We did not observe any DLTs in the five patients treated with rivoceranib 300 mg once a day and pembrolizumab 200 mg every 3 weeks, although several patients did experience treatment-related AEs. Hence, we expanded the enrollment of patients at dose level 1 (300 mg). Despite doses of up to 850 mg rivoceranib daily, as a single agent, in several previous trials focused on gastric cancer, patients with metastatic urothelial carcinoma, had difficulty tolerating 300 mg rivoceranib daily in combination with pembrolizumab beyond the initial DLT period in this trial. All toxicities were manageable with no treatment-related deaths.In this heavily-pretreated population of patients, 3 of 4 patients (those with measurable disease burden) received clinical benefit and had stable disease with disease shrinkage while on trial, including two patients who had previously progressed on pembrolizumab, one of which had a significant reduction in metastatic burden as shown in Fig. In conclusion, amongst a heavily pretreated population of patients with metastatic urothelial, gastric and gastroesophageal adenocarcinoma, rivoceranib 300 mg daily combined with pembrolizumab can be used safely. Moreover, the majority of patients received clinical benefit from treatment, and none experienced any DLTs.