Abstract 128P
Background
In a randomized controlled pivotal phase III pre-surgery administration of investigational proinflammatory biologic (LI) with CIZ (single low dose cyclophosphamide IV, indomethacin (po tid) and Zinc (po, daily) multivitamins + Standard of Care (SOC) to oral and soft-palate SCCHN subjects, resulted in significantly prolonged overall survival (OS) in the NCCN Guidelines defined low risk (LR) intent to treat (ITT) population vs SOC alone (NCT01265849).
Methods
Available samples (453 ITT; 210 LR ITT) meeting entry criteria (AJCC Stage III/IVa OSCC, soft-palate SCCHN, Tx naïve) randomized 3:1:3 to Tx arms LI (+/- CIZ) + SOC or SOC alone. LI was injected 200IU peritumorally and 200IU peri-lymphatically daily, 3-weeks before surgery. All study subjects were to receive SOC (per NCCN, LR RTx, high risk CRTx post-surgery). Follow-up was comparable (56-57 months median per Tx group). Tumor HP samples were stained/quantitated for 20 biomarkers (5 tumor cell, 15 tumor microenvironment), 2 ratios, and 14 marker combinations prospectively defined, including low/high thresholds for each biomarker, ratio; combinations defined as +ve or -ve. Defined prospective interactions models (all subjects) allowed three-way interactions assessment for risk groups, biomarker/combination level and Tx, to analyze Tx efficacy for OS, PFS, LRC outcomes using proportional hazard models.
Results
HP samples (n=453) were representative of the overall population (n=923). Broad demonstration beyond 2.5% chance always favored LI+CIZ+SOC vs SOC (see below). Table: 128P
| Proportion statistically significant, p<0.05 | ||
| Overall (n=453) | Low Risk (n=210) | |
| Overall survival | 26/188 | 21/94 |
| Progression free survival | 17/188 | 16/94 |
| Local regional control | 18/188 | 17/94 |
| Totals | 61/564 (10.8%>>2.5%) | 54/282 (14.7%>>2.5%) |
All advantages favored LI+CIZ+SOC vs SOC (only seen in LR)
Conclusions
Efficacy (OS, PFS, LRC) was seen for multiple biomarkers (tumor: p16, PDL1, TME: CD4, CD8, CD3, FOXP3, CD20, CD68, CD163, CD1A, immune cells: PD1, CTLA4, PDL1, and CD25), ratios (CD4/CD8, CD8/FOXP3), and pre-defined combinations confirm and support LI OS efficacy.
Clinical trial identification
Protocol: CS001P3, 30June2010; NCT01265849.
Editorial acknowledgement
Legal entity responsible for the study
CEL-SCI Corporation.
Funding
CEL-SCI Corporation.
Disclosure
J. Timar: Other, Institutional, Principal Investigator, Relationship is for contract research: CEL-SCI. E. Talor: Financial Interests, Personal and Institutional, Full or part-time Employment, Including Stocks/Shares: CEL-SCI. P. Lavin: Other, Institutional, Advisory Role, Including Funding: CEL-SCI. A. Kiss: Other, Institutional, Principal Investigator, Relationship is for contract research: CEL-SCI. D. Markovic: Other, Institutional, Other, Relationship is for contract research: CEL-SCI. J. Cipriano: Financial Interests, Personal and Institutional, Full or part-time Employment, Including Stocks/Shares: CEL-SCI. All other authors have declared no conflicts of interest.