Analysis of Clinical Benefit Using DNG64- CAR-V Chimeric Tumor Targeted Amphotropic RNA Vector in CCNG1 Expressing Cancers

Background/Aim: Metastatic cancer is almost always fatal, with few promising clinical options. DNG64-CAR-V is an off-the-shelf, replication-incompetent Chimeric Amphotropic tumor-targeted RNA Vector encoding a cytocidal Cyclin G1 (CCNG1) inhibitor construct. Patients and Methods: CCNG1 expression level in cancer types; Clinical benefit rate or CBR [complete response (CR), partial response (PR), or stable disease (SD)], confirmed by computed tomography or magnetic resonance imaging by RECIST v1.1; Overall response rate (ORR) and incidence and severity of adverse events were assessed. Eligibility criteria included: Previously treated male or female patients ≥12 years old with advanced sarcomas and patients ≥18 years old with advanced pancreatic ductal adenocarcinoma (PDAC), breast carcinoma or ovarian adenocarcinoma; Patients were treated with DNG64-CAR-V (1.7×10¹⁰ VC 3× a week × 3 weeks/month) plus metronomic low doses of FDA approved drugs (DNG64-CAR-V+); Statistical analysis was performed with Simon 2-stage design with Type I error rate=0.1 and power=0.8. A CBR ≥30% warrants a Phase II study using DNG64-CAR-V+ for CCNG1 expressing tumors. Results: Ten subjects with CCNG1 expressing sarcomas (n=6), PDAC (n=2), breast ductal carcinoma (n=1), and ovarian adenocarcinoma (n=1) were treated with DNG64-CAR-V+. Five of 10 (50%) had PR; 9/10 (90%) had clinical benefit. Median progression-free survival was 6.7 months for sarcoma. No serious treatment-related adverse event is reported. Conclusion: A response rate of 50% and a CBR of 90% for all groups meet the Simon 2-stage threshold of CBR >30%, thereby qualifying all groups for a Phase II study using DNG64-CAR-V+ in CCNG1 expressing advanced cancers.