54P Oncolytic virus combined PD-1 antibody toripalimab in advanced lung cancer with liver metastases: An early stage, single arm, study (TROJAN 2201)

The efficacy of checkpoint inhibitors are far from satisfied in lung cancer patients with liver metastases. Oncolytic virus can enhance the efficacy of PD-1/PD-L1 antibody in vitro/vivo. In this study, we evaluate the safety and efficacy of oncolytic virus H101 plus PD-1 antibody Toripalimab for liver metastasis-lung cancer advanced patients who have progressed and failed after EGFR-TKIs, chemotherapy or checkpoint inhibitors treatment. The patients refractory to previous several lines of standard treatment were injected with recombinant human adenovirus 5 (1012 vp or 2×1012vp) locally for liver metastases plus toripalimab (3mg/kg) systemic therapy every 2 weeks until progression or intolerable toxicity. The two primary end points were investigator-assessed safety and objective response rate (ORR) and the secondary end points included progression-free survival (PFS) and disease control rate (DCR). Efficacy was assessed every 2 months by investigators according to mRECIST v1.1 criteria. Blood samples were collected from patients prospectively. From January 26, 2021 to July 15, 2022, ten patients were enrolled and received at least 1 cycle of the combination regimen. The most common treatment-related adverse events (TRAEs) were grade 1-2 fever, which was occurred in 9 (90%) of 10 patients. No deaths and other SAE were judged to be treatment-related. Six among the 10 patients received at least 3 cycles of the combination regimen and 5 were evaluable for efficacy analyses as one patient was lost to follow-up. Two of five (40%) patients (one small cancer and one adenocarcinoma) acquired partial remission (PR) after 3 cycles of the combination therapy, including one patient remained remission for 11 months. Two patients (40%) (one small cancer and one adenocarcinoma) achieved stable disease (SD) and the other one adenocarcinoma patent (20%) had progressive diseases (PD). Our results confirm that the combination of recombinant human adenovirus type 5 plus toripalimab has shown an acceptable safety profile and the preliminary efficacy in those who refractory to previous several lines of standard treatment, deserved further investigation in randomized trials.