Neoadjuvant cytokine (IRX-2) immunotherapy for resectable oral cavity carcinoma: Final results of the INSPIRE trial

Oral cavity squamous carcinoma is characterized by alterations in cell mediated tumor immunity including a lack of immune reactive tumor infiltrating lymphocytes (TILs). To determine if a novel neoadjuvant injection of a multi-cytokine biologic (IRX-2) can restore immune reactivity and enhance patient survival, a randomized Phase 2 clinical trial was conducted in patients with Stage II-IV OSCC undergoing surgical resection (NCT 02609386). The intention-to-treat (ITT) enrollment included 105 previously untreated patients, however 9 were excluded from the secondary endpoint analysis group for wrong histology, no treatment or patient refusal. A total of 96 patients comprised the final analytic group and were randomized (2:1) to receive the IRX-2 regimen (Regimen 1) compared to the identical regimen without IRX-2 cytokines (Regimen 2). Toxicity, tumor and immune responses, event-free (EFS) and overall (OS) survival were determined. Kaplan-Meier estimates for OS and EFS and inferential comparisons and asymptotoic log-rank testing between the two treatments were determined. In prior preliminary analysis, significant increases in TILs and DMBT1 gene expression were noted for the IRX arm. No significant correlations of immunologic or tumor responses with survival outcomes were found. For the ITT population (n = 105) there were no significant differences in OS by treatment arm. OS [95 % CI] at 48 mo. was 70.4 [57.6, 80.0] vs 66.3 [47.5, 79.8] mos. (Regimen 1 vs Regimen 2, respectively). Conclusions: Significant differences in survival were not seen, however, the trial demonstrated the feasibility of the neoadjuvant immunotherapy and differing immune modulation in each treatment arm. No correlations of immune biomarkers or tumor size changes with survival outcomes were identified.