935P - Prognostic significance of diagnostic staging in treatment naïve, resectable locally advanced primary oral cavity squamous cell carcinoma for neoadjuvant leukocyte interleukin injection immunotherapy

Background

In a randomized controlled pivotal Phase III study neoadjuvant investigational proinflammatory biologic Leukocyte Interleukin Injection (LI) administered pre-surgery with CIZ (single low dose cyclophosphamide IV, indomethacin (po tid) and Zinc (po, daily) multivitamins + Standard of Care (SOC) to locally advanced treatment naïve oral and soft-palate SCCHN subjects, resulted in significantly prolonged overall survival (OS) in the locally advanced, node negative (N0) population with tumor cell PDL-1 proportional score (TPS) categorized as ≤10, in intent to treat (ITT) population vs SOC alone.

Methods

Consenting subjects with available samples (n=114 ITT, 99 oral only) meeting entry criteria (AJCC Stage III/IVa OSCC, soft palate, treatment (Tx) naïve) randomized 3:1:3 to Tx arms LI (+/- CIZ) + SOC or SOC alone (control). LI was injected 200IU (as IL-2 equivalent) peritumorally and 200IU peri-lymphatically 5x/week, for 3-consecutive weeks before surgery. All study subjects were to receive SOC per NCCN guidelines post-surgery. Follow-up was comparable (56 months median per Tx group). Tumor histopathology (HP) samples obtained at surgery were stained/quantitated for PD-L1 (TPS). Prospective models allowed Tx efficacy assessments for OS, using proportional hazard models with three pre-defined covariates (tumor location, stage, geographic region); hazard ratios (HRs) for LI+CIZ+SOC (GA) vs SOC alone (GC) were calculated.

Results

GA treatment modality was superior to GC for OS 0.35 HR (95% CI 018, 0.66; Wald p=0.0015) for oral and soft palate, and OS oral cavity only 0.36 HR (95% CI 0.18, 0.73; Wald p=0.0044). OS advantage at 60 Month favoring GA vs GC - for oral cavity + soft palate was 28% (73% vs 45%), Log rank p=0.0015 and for oral cavity only was 27% (73% vs 46%), Log rank p=0.0055.

Conclusions

Advantages for OS (HR 0.35 Oral + Soft Palate, and HR 0.36 Oral cavity) over control support LI’s effect on efficacy in the target/treated population.

Clinical trial identification

NCT01265849.

Editorial acknowledgement

Legal entity responsible for the study

CEL-SCI Corporation.

Funding

Boston Biostatistics Research Foundation is an independent entity contracted by CEL-SCI Corporation to analyze the data from the study, which was sponsored by CEL-SCI Corporation.

Disclosure

P. Lavin: Financial Interests, Personal and Institutional, Advisory Board: CEL-SCI Corporation. J. Timar: Financial Interests, Institutional, Principal Investigator: CEL-SCI Corporation. D. Markovic: Other, Institutional, Other: CEL-SCI Corporation. J. Cipriano, E. Talor: Financial Interests, Personal, Full or part-time Employment: CEL-SCI Corporation.