Phase I/II trial of OncoVEXGM-CSF combined with radical chemoradiation (CRT) in patients with newly diagnosed node-positive stage III/IV head and neck cancer (HNC)

Abstract

14095 Background: OncoVEXGM-CSF is a second generation oncolytic herpes virus expressing GM-CSF which has previously completed a Phase I study with evidence of anti-tumor activity. Combination of OncoVEXGM-CSF with CRT has additionally demonstrated significant pre-clinical anti-tumor activity. Methods: Patients (pts) with newly-diagnosed node-positive stage III/IV HNC were enrolled in cohorts of 4. Patients received radiotherapy (70 Gy/35 fractions to gross disease, 50 Gy/25 fractions to elective areas) with concomitant cisplatin (100mg/m2 days 1, 22, 43). Four doses of intranodal virus were given on days 1, 22, 43 and 64 as follows: Cohort 1 - 106, 106, 106, 106; Cohort 2 -106, 107, 107, 107; Cohort 3 - 106, 108, 108, 108 pfu/ml. Patients underwent neck dissection 4–6 weeks after the last dose. Endpoints were safety, viral replication and anti-tumor activity. Results: Eight pts have completed the protocol. Nodal stages were N2a (2 pts), N2b (3), N2c (2), N3 (1). Compliance with the CRT schedule was 100%. In Cohort 1, 1 pt received only 3 doses of virus because of early complete response (CR). In Cohort 2, 1 pt received 3 doses and 1 pt 2 received doses because of early CR. Neck dissection was undertaken as planned in all but 1 pt. CRT-related toxicities were not exacerbated by OncoVEXGM-CSF. Non-CRT-related toxicities were mild (grade 1–2 fever and injection site pain). No dose-limiting toxicities were seen. In pts in whom nodal biopsy was possible during treatment, evidence of viral replication was seen. Clinical responses in the primary site (7 pts) and nodal disease (8 pts) were impressive which anecdotally appeared to be greater than would be expected with chemoradiation alone. Pathological CR was confirmed at the primary tumour site in 6 pts and in the neck in 3 pts after neck dissection. Extensive tumour necrosis was seen in all injected nodes. Extensive staining for OncoVEX was also seen including in adjacent uninjected nodes demonstrating considerable intratumoral virus spread. Conclusions: Combination of OncoVEXGM-CSF and CRT is well tolerated with promising anti- tumor activity. Recruitment to the final dose-escalation cohort has now been completed. No significant financial relationships to disclose.