937P Survival outcomes in phase I trial combining VCN-01 and durvalumab (MEDI4736) in subjects with recurrent/metastatic head and neck squamous cell carcinoma refractory to previous immunotherapy treatment

VCN-01 is an oncolytic adenovirus expressing hyaluronidase that increases immune check-point inhibitor uptake in preclinical models suggesting it could reduce resistance to anti-PD(L)-1 therapies. Initial results from phase 1 trial NCT03799744 showed that sequential administration of VCN-01 and Durvalumab is feasible with an acceptable safety profile. Here we present the clinical outcomes data. VCN-01 at 3,3E12 and 1E13 viral particles [vp] were administered with a fixed dose of Durvalumab (1500 mg) in a 3+3 design in R/M HNSCC pts previously treated with anti-PD(L)-1 agents. Concomitant (single dose VCN-01 + Durvalumab on day 1, CS), and sequential (single dose of VCN-01 on day -14 + Durvalumab on day 1; SS) schedules were tested. Durvalumab continued q4 weeks until progression in both schedules. Fresh tumor biopsies were taken at baseline, post-VCN-01 and post-Durvalumab. 20 patients were enrolled (median prior lines: 4, range: 1-7), from which 6 in the CS (all 3.3E12 vp) and 12 in the SS (6 at 3,3E12vp and 6 at 1E13 vp) were evaluable for response. Objective response rate (ORR), median PFS and OS (95% CI) in the CS at 3,3E12vp were 0% 1,7 months (1.6-NE) and 10.4 months (8.9-NE), respectively. For SS patients at 3.3E12 vp, ORR, median PFS and OS were 16%, 3.7 months (2.2-NE) and 15.5 months (15.1-NE) respectively. Values for SS patients at 1E13 vp were 0%, 2.1 months (1.4-NE) and 15+ months. 11 patients (61.1%) were alive >12 months (2 in CS; 5 in SS at 3.3E12 vp, 4 in SS at 1E13 vp). Unexpectedly most of them appeared to benefit from subsequent treatment. The 3 patients with the longest survival showed immune-mediated DLT. Increase of PDL1-CPS (16/21; p=0.013) and CD8 T-cells (12/21; p=0.007) from baseline were found in tumor biopsies both post-VCN-01 and post-Durvalumab. A correlation between OS and CPS at D8 was observed (p=0.005). Viral genome analysis and other biologic markers confirmed sustained VCN-01 replication. Encouraging survival was observed in patients progressing to anti-PD(L)-1 agents after systemic VCN-01 with Durvalumab. VCN-01-induced upregulation of PD-L1, which correlated with enhanced patient survival.