Phase III IT-MATTERS trial of Multikine in head and neck cancer announces 10-year results for FDA submission

Data collected during the Phase III trial that will be submitted to FDA in support of the Proposed Indication are: Partial and complete tumor responses within 3 weeks and before surgery (objective responses per RECIST): 8.1% (32/395) objective response rate (ORR) for Multikine+CIZ patients in the intent-to-treat (ITT) population versus zero in the SOC group (n=394). 15.2% (24/158) ORR for Multikine+CIZ patients in the lower-risk-for-recurrence arm versus zero in the SOC group (n=168). Two-sided Fisher Exact p-values <0.0000001 for orr. complete responses before surgery were seen in 5 multikine+ciz patients. objective response before surgery was prognostic predictive of improved overall survival (os) and significant for reduced death rate : in the itt population, 22.2% death rate versus 54.1% death rate (multikine objective responders versus multikine non-responders; two-sided fisher exact p-value><0.0001; hr="0.301" [95% ci 0.16, 0.566]). in the lower-risk-for-recurrence arm, 12.5% death rate versus 41.0% death rate (multikine+ciz objective responders versus multikine+ciz non-responders; two-sided fisher exact p-value="0.0101;" hr="0.246" [95% ci 0.077, 0.787]). data that will be provided to fda to confirm efficacy in the proposed indication: analysis of the lower-risk-for-recurrence arm was pre-specified in the original study protocol and in the statistical analysis plan. this arm comprised about 40% of all study participants. 14.1% absolute os advantage at 5-years in the lower-risk-for-recurrence arm (62.7% vs 48.6%) for multikine+ciz patients versus soc patients. os benefit was also shown at 1, 2, 3, and 4 years. nearly 4-year increase in median overall survival in the lower-risk-for-recurrence arm (101.7 months for multikine+ciz versus 55.2 months for the soc). histopathological analysis confirmed the effect of multikine, as 61 markers, ratios, and combinations showed a statistically significant effect in the lower-risk-for-recurrence arm (two-sided p><0.05) favoring multikine+ciz versus the soc for os, progression free survival, and loco-regional control outcomes. additional (confirmatory) progression-free survival benefit in the lower-risk-for-recurrence arm was observed for multikine+ciz versus the soc. no excess safety issues: the overall incidence of adverse events and serious adverse events in the multikine arms was not substantially different versus the soc.></0.05)></0.0001;></0.0000001>

The pivotal Phase III trial is intended to support a Biologics Licensing Application to FDA, which has not yet been submitted. FDA is the only U.S. entity authorized to determine safety and efficacy. Multikine is currently not FDA approved. The “Proposed Indication” for Multikine that will be submitted to the FDA in a license application will be limited by certain eligibility criteria to patients who would be deemed by NCCN Guidelines as having a lower risk for tumor recurrence. The Standard of Care for lower risk for tumor recurrence advanced primary head and neck cancer patients is surgery followed by radiotherapy, but not chemotherapy. Note that the term “lower risk for recurrence” should not be confused with a low risk of death, because the 5-year survival for such patients is still less than 50%, even after receiving the current standard of care (SOC). The Proposed Indication for Multikine would cover an estimated 210,000 patients globally each year.