Abstract 940P
Background
OBP-301 is a novel, human telomerase reverse transcriptase gene (hTERT) promoter regulated replication-competent adenovirus. Its replication, oncolysis and dissemination are restricted to cells that express the hTERT promoter, which is highly expressed in a variety of human cancers including liver cancer. We assessed the safety and efficacy of intratumoral (IT) injection of OBP-301 in advanced hepatocellular carcinoma (HCC).
Methods
Open-label, phase I dose-escalation trial (3+3 design) was performed on 20 patients with advanced HCC, progressed after standard treatments. OBP-301 administration was done by ultrasound-guided IT injection at the primary tumor. 1×1010virus particles (VP), 1×1011 VP, 1×1012 VP, 3×1012 VP were administered in single dose cohort, respectively (Cohort 1-4). 2×1012 VP ×3 times every 2 weeks was administered in multiple doses (Cohort 5).
Results
A total of 3 subjects in each of Cohorts 1-4 received single escalating doses of OBP-301, 8 subjects were enrolled in Cohort 5, and 6 of them received all doses as scheduled. The single dose and multiple dose of OBP-301 were well-tolerated. Maximum tolerated dose (MTD) was considered as > 6×1012 VP/subject. The frequency of treatment-emergent adverse events (TEAEs) related to OBP-301 was higher in Cohorts 4-5 than in Cohorts 1-3. The most frequently reported TEAEs related to OBP-301 were influenza-like illness (30.0%), followed by pyrexia (15.0%) and fatigue, platelet count decrease, abdominal distension, and anemia (10.0% each). OBP-301 replication-dependent dissemination in blood was observed. Increased level of CD8+ T cells was shown and maintained by 50% subjects in Cohort 4-5 after OBP-301 IT injection. Overall intrahepatic mRECIST response was observed in 7 (39%) subjects with stable disease (SD) and 11 (61%) with progressive disease (PD). Best target response was observed in 14 subjects with SD (78%) and 4 (22%) subjects with PD.
Conclusions
Multiple IT injections of OBP-301 are well-tolerated in advanced HCC. Although antitumor activity of the study medication alone could not be demonstrated, obviously, SD observed as best local response was higher than as overall response.
Clinical trial identification
CT-OT-21/ NCT02293850.
Editorial acknowledgement
Legal entity responsible for the study
Medigen Biotechnology Corporation, Oncolys Biopharma Incorporation.
Funding
Medigen Biotechnology Corporation, Oncolys Biopharma Incorporation.
Disclosure
J. Heo: Financial Interests, Personal and Institutional, Research Grant: Roche Holding AG; Non-Financial Interests, Personal and Institutional, Invited Speaker: Gilead. S. Chang: Financial Interests, Personal, Ownership Interest: Medigen Biotechnology Corp.; Financial Interests, Personal, Stocks/Shares: Medigen Biotechnology Corp. Y. Urata: Financial Interests, Personal, Ownership Interest: Oncolys BioPharma Inc.; Financial Interests, Personal, Stocks/Shares: Oncolys BioPharma Inc. All other authors have declared no conflicts of interest.