Replies to post #42264 on Cel Sci Corporation (CVM)

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IT-MATTERS Phase 3 Trial Results Summary

This release summarizes the results recently posted on clinicaltrials.gov for the overall ITT population as well as the subjects constituting the Proposed Indication representing 41.2% of the study overall ITT population. ( See https://clinicaltrials.gov/ct2/show/results/NCT01265849?term=multikine&draw=2&rank=2 ) Please refer to the clinicaltrials.gov presentation of the data for further information on study design and study data.

Objective Responses Before Surgery (partial and complete tumor response per RECIST, confirmed at surgery by pathology) : In the overall ITT population, objective responses before surgery (sometimes also called “early responses”) were observed in 45 subjects who received Multikine for 3 weeks; no such responses were observed in the SOC alone (control) (p<0.00000001).

Five subjects who received Multikine+CIZ had complete tumor responses confirmed at surgery.

In the overall ITT population (n=923), objective responses were seen in:
8.5% of Multikine-treated subjects (45/529).
8.1% of the Multikine+CIZ treatment arm (32/395).
9.7% of the Multikine without CIZ treatment arm (13/134);
0% of the SOC alone (control) treatment arm (0/394).

In the Proposed Indication (n=380), objective responses were seen in:
16.0% of Multikine-treated subjects (34/212).
15.2% of the Multikine+CIZ treatment arm (24/158).
18.5% of the Multikine without CIZ treatment arm (10/54); and
0% of the SOC alone (control) treatment arm (0/168).

Objective Responses Before Surgery Were Prognostic For Survival with a Significant Decrease in Death Rate:
In the overall ITT population (n=923), the 22.2% death rate among Multikine objective responders before surgery (n=45) was significantly lower (two-sided Fisher Exact test p<0.0001; HR=0.301) than the 54.1% death rate for the remaining Multikine non-responders (n=484);

In the Proposed Indication (n=380):
the 17.6% death rate among all Multikine objective responders before surgery (n=34) was significantly lower (two-sided Fisher Exact test p=0.0067; HR=0.348) than the 42.7% death rate for the remaining Multikine non-responders (n=178).
the 12.5% death rate among Multikine+CIZ objective responders before surgery (n=24) was significantly lower (two-sided Fisher Exact test p=0.0101; HR=0.246) than the 41.0% death rate for the remaining Multikine non-responders (n=134).

Significant OS advantage in the Proposed Indication for the Multikine+CIZ treatment arm versus the SOC control:
5-year absolute OS advantage of 14.1% (62.7% vs 48.6%);
proportional hazards two-sided p=0.0236;
0.68 hazard ratio equating to a 47% OS prolongation; and
3-year and 4-year absolute OS advantage of 4.9% and 9.5%, respectively, are supportive.
In the overall ITT population, no statistically significant OS difference was seen between the two main comparator groups (proportional hazards two-sided p=0.4128). It is believed that the higher-risk-for-recurrence patients in the overall ITT were too sick to tolerate the extra three-weeks before surgery for the Multikine treatment and also that chemotherapy may impair Multikine’s immunological mechanism of action.

Nearly Four-Year Median OS Benefit : In the Proposed Indication, the median OS for those receiving Multikine+CIZ was 101.7 months versus 55.2 months for the control, a survival improvement of almost four years. The Multikine treatment arm without CIZ in the Proposed Indication also had better median OS than control (68.2 months vs. 55.2 months).

Progression-Free Survival (PFS) : In the Proposed Indication, there was confirmatory PFS difference between the two main comparator groups (HR=0.76; proportional hazards two-sided p=0.0896). In the overall ITT population, there was no statistically significant PFS difference between the two main comparator groups (proportional hazards two-sided p=0.3728).

Locoregional Control (LRC) : In the Proposed Indication, there was no statistically significant LRC difference between the two main study groups (proportional hazards two-sided p=0.4082). In the overall ITT population, there was no statistically significant LRC difference between the two main comparator groups (proportional hazards two-sided p=0.8020).

Significant Histopathological Results : OS, PFS, and LRC were examined using a proportional hazards model to assess the interactions between histopathology (HP) cellular marker expression levels, risk group (lower and higher), and treatment in the two main comparator groups. Twenty HP markers were classified as low, medium, and high. Two HP ratios were classified as low, medium, and high. Fourteen HP combinations were classified as low and high. These resulted in 94 possible comparisons for each of OS, PFS, and LRC.

Significance favoring Multikine+CIZ vs. control (two-sided p<0.05) was observed in the Proposed Indication as follows:
OS: 14 markers, 2 ratios, and 9 combinations;
PFS: 11 markers, 1 ratio, and 5 combinations;
LRC: 9 markers, 1 ratio, and 6 combinations;

Combined (summed across endpoints), significance was reached for 21.6% (61/282) of the total possible comparisons, and the one-sided 97.5% confidence bound on the fraction significance was 16.3% which exceeds 5% chance alone.

No excess safety issues:

The overall adverse event rates were 92.4% for the Multikine+CIZ treatment arm; 95.9% for the treatment arm receiving Multikine without CIZ, and 96.1% for the SOC alone (control) treatment arm.

The overall serious adverse event rates were 53% for the Multikine+CIZ treatment arm, 50.7% for the treatment arm receiving Multikine without CIZ, and 52.7% for the SOC alone (control) treatment arm.

The incidence of adverse events and serious adverse events noted in the Multikine arms was not substantially different from those in control.