893P - Tumor node stage shift following leukocyte interleukin injection neoadjuvant extends overall survival in treatment-naïve locally advanced oral cavity/soft palate squamous cell carcinoma

Background

A 3-week pre-surgery peri-tumoral/peri-lymphatic administration of a pro-inflammatory cytokine complex biologic (LI) with CIZ (single low dose cyclophosphamide IV, 300 mg/m²), indomethacin (po 25mg tid) and yinc multivitamins (po 15-45mg yinc) + Standard of Care (SOC) to treatment-naïve oral/soft palate (OSP) locally advanced SCC, resulted in CRs/PRs prior to surgery (RECIST 1.0) (pathology confirmed) significantly extend overall survival (OS) in NCCN-defined Lower risk for recurrence (LR) intent to treat (ITT) population vs SOC alone. Joint TN (jTN) stage determined at screening, prior to planned surgery, confirmed at surgery.

Methods

Subjects (923 ITT; 380 [LR], 467 higher-risk) AJCC Stage III/IVa OSP SCC, treatment naïve were randomized 3:1:3 to treatment (Tx) arms LI (+/- CIZ) + SOC or Control (SOC only). LI treated (Tx) received ½ dose 200IU peritumorally + ½ dose daily peri-lymphatically x5/wk for 3 weeks before surgery. Each Tx had comparable (55-56 months median) follow up.

Results

TN data were available at screening and surgery for 815/923 ITT subjects; and 43 pre-surgery responders (R), a general trend of worsening in jTN stage entry to surgery with 6-7% more improved jTN for both LI-Tx vs SOC. Table: 893P

No significant differences at screening for subsequent R vs non-R; significant improvement in jTN stage from screening to surgery for LI R (88% improved); jTN differences (p<0.0001) between LR vs HR allowing differentiation of LR from HR at entry. LI-Tx subjects with jTN (I) had >50% 5-year overall survival (OS), while 5-yr OS was <50% for SOC. LI+CIZ+SOC 5-yrs OS >60% (I vs W) p <0.0001; 5-yr OS 30% (W), 50% (Same); LR LI+CIZ+SOC R 5-yr OS >75%, p <0.0001.

Conclusions

jTN differentiated LR vs HR at entry enabling us to search for LR subjects as ideal for neoadjuvant LI-Tx to extend OS. LI neoadjuvant jTN improvement is highly associated with OS joining pre-surgery response to LI as another surrogate marker for OS.

Clinical trial identification

(IT-MATTERS; NCT01265849).

Editorial acknowledgement

Legal entity responsible for the study

CEL-SCI Corporation.

Funding

CEL-SCI Corporation.

Disclosure

J. Timar: Financial Interests, Institutional, Other: CEL-SCI Corp. P. Lavin: Financial Interests, Personal and Institutional, Officer: CEL-SCI Corp. J. Cipriano: Financial Interests, Personal and Institutional, Officer: CEL-SCI Corp. D. Markovic: Financial Interests, Personal and Institutional, Leadership Role: Ergomed plc. E. Talor: Financial Interests, Personal and Institutional, Officer: CEL-SCI Corp.