Abstract 690P
Background
Our phase 3 study (clinicaltrials.gov NCT01265849) evaluated a 3-week pre-surgery administration of an investigational natural cytokine complex biologic (LI) with/without CIZ (low dose cyclophosphamide), indomethacin, and zinc in oral and soft-palate SCCHN + standard of care (SOC) vs SOC alone.
Methods
Early response (ER) pre-surgery was evaluated by RECIST for all subjects (923 ITT; 380 Low Risk [LR] ITT) in addition to OS at 5-yrs. Subjects were randomized 3:1:3 to treatment arms LI (+/- CIZ) + SOC or to Control (SOC alone). LI was administered daily for 3-weeks (x5/wk) before surgery. Overall median follow-up was 4.7 years.
Results
There were 45 ERs and 462 deaths (50.1%). ERs were most common in LR and only seen in the two LI treated groups, but never seen in SOC alone; death rates fell significantly for ERs vs non-responders. ER confirms OS advantage: LR LI+CIZ+SOC exhibited 306% OS prolongation for 15.2% ERs. Assuming no OS prolongation for the remaining 84.8%, this equates to a 46.5% OS gain corresponding to a 0.68 HZR (1/1.465) as observed for the LR LI+CIZ+SOC group. There was a 46-month median OS advantage for LR LI+CIZ+SOC vs LR SOC. Table: 690P
| Treatment Group | Site Determined Risk Classification | |||
| Early Response Rate | ||||
| Low Risk | High Risk (HR) | Unclassified | Totals | |
| LI+CIZ+SOC | 15.2% | 3.5% | 2.7% | 8.1% |
| LI+SOC | 18.5% | 4.3% | 0% | 9.7% |
| Combined LI | 16.0% | 3.7% | 2.1% | 8.5% |
| SOC | 0% | 0% | 0% | 0% |
| 2-sided Fisher Exact Test | P<0.0001 | P=0.0062 | NS | P<0.0001 |
| Death Rate | ||||
| Response Outcome | Combined LI | LR Combined LI | LR LI+CIZ+SOC | |
| Responders | 22.2% | 17.6% | 12.5% | |
| Non-responders | 54.1% | 42.5% | 40.7% | |
| 2-sided Fisher Exact Test | P<0.0001 | P=0.0068 | P=0.01 | |
| Hazard Ratio (HZR) | ||||
| Combined LI | LR Combined LI | LR LI+CIZ+SOC | ||
| HZR | 0.301 | 0.348 | 0.246 | |
| 2-sided 95% CI | 0.16, 0.566 | 0.152, 0.801 | 0.077, 0.787 | |
| 2-sided Wald Test | P<0.0001 | P=0.0067 | P=0.01 |
Conclusions
ER was only observed for the LI treatments. Multiple ERs were observed; LR (n=34), HR (n=10), and 1 subject without risk classification. ER from LI treatment is not only prognostic but also predicts a most favorable OS outcome.
Clinical trial identification
Protocol: CS001P3, 30June2010, NCT01265849.
Editorial acknowledgement
Legal entity responsible for the study
CEL-SCI Corporation.
Funding
CEL-SCI Corporation.
Disclosure
P. Lavin: Non-Financial Interests, Institutional, Advisory Role, Including Funding: CEL-SCI. E. Talor: Financial Interests, Personal and Institutional, Full or part-time Employment, Including Stocks/Shares: CEL-SCI. D. Markovic: Institutional: CEL-SCI. J. Cipriano: Financial Interests, Personal, Officer, Including Stocks/Shares: CEL-SCI.