Phase I/II dose escalation study of OncoVexGM-CSF and chemoradiotherapy (CRT) in untreated stage III/IV squamous cell cancer of the head and neck (SCCHN)

Abstract

6018 Background: OncoVEXGM-CSF is a gene deleted (ICP34.5-/ICP47) oncolytic HSV-1 that encodes human GM-CSF. OncoVEXGM-CSF causes direct oncolytic tumour cell destruction and immune activation by releasing tumour antigens and GM-CSF, effects that may co-operate with CRT to increase loco-regional control in SCCHN. Methods: Patients (pts): Stage III/IVA SCCHN, N1-N3, ECOG 0–1, normal haematologic, biochemical, immune function. Pts received CRT (70 Gy/35 fractions with concomitant cisplatin 100 mg/m2 (d 1, 22, 43) and dose-escalating (106, 106, 106, 106 pfu/mL [cohort 1]; 106, 107, 107, 107 [cohort 2]; 106, 108, 108, 108 [cohort 3]) OncoVEXGM-CSF by intratumoral injection (d 1, 22, 43, 64). Pts underwent neck dissection 6–10 weeks after CRT. Primary endpoints were safety and recommended dose/schedule for future study. Secondary endpoints were anti-tumor activity, viral replication and HSV antibody levels. Results: 17 pts were treated, 9 at the top dose (15 males, median 58 years). DLT and MTD were not reached. There were no delays to CRT delivery. 13 pts had PR or CR by CT, 5 pts achieving rapid CR following only 2 or 3 viral doses. Pathological CR was observed in 94% of pts at neck dissection. Transient low level injection site viral shedding was seen in 3 pts. HSV was detected in injected and adjacent uninjected tumors by qPCR and immunohistochemistry, including at levels higher than the input dose, indicating replication. All seronegative pts seroconverted. 11 of 17 (65%) pts remain in remission at median follow-up of 23 months. No pts had local relapse, 1 pt had a new primary tumor, 3 pts distant metastatic disease, 1 pt intercurrent disease, 1 pt lost to follow up. Conclusions: OncoVEXGM-CSF combined with cisplatin-based CRT is well tolerated in pts with SCCHN. Viral replication was confirmed. Long-term locoregional control was achieved in 100% of pts, 65% of pts remaining in complete remission. Further study is warranted. [Table: see text]