Safety and dose escalation of the targeted oncolytic adenovirus OBP-301 for refractory advanced liver cancer: Phase I clinical trial

OBP-301 is an oncolytic adenovirus modified to replicate within cancer cells and lyse them. This open-label, non-comparative, phase I dose-escalation trial aimed to assess its safety and optimal dosage in 20 patients with advanced hepatocellular carcinoma. Good tolerance was shown with a maximum tolerated dose of 6 x 1012 viral particles. The most common treatmentemergent adverse events were influenza-like illness, pyrexia, fatigue, decreased platelet count, abdominal distension, and anemia. Cohorts 4 and 5 had approximately 50% higher levels of CD8+ T cells in the peripheral blood after injection. The best target response occurred in 14 patients, 4 of whom had progressive disease. Multiple intratumoral injections of OBP-301 were well tolerated in patients with advanced hepatocellular carcinoma. The stable disease rate for the injected tumors was greater than the overall response rate, even with no obvious tumor response. OBP-301 might have a greater impact on local response as histological examination revealed that the presence of OBP-301 was consistent with the necrotic area at the injection site. Increased infiltration of CD8+ T cells and <1% PD-L1 expression were observed in tumors after injection. Improved antitumor efficacy might be achieved in future studies via viral injection with volume adjustment and in combination with other immuno-therapeutics.

Automated summary

OBP-301 is a modified oncolytic adenovirus that can replicate within cancer cells and cause their lysis. This phase I trial aimed to determine the safety and optimal dosage of OBP-301 in patients with advanced hepatocellular carcinoma. The study found that OBP-301 was well tolerated, with a maximum tolerated dose of 6 x 1012 viral particles. Injection of OBP-301 resulted in increased levels of CD8+ T cells and showed potential antitumor efficacy.