The FDA has removed a clinical hold on Cel-Sci Corp.'s primary clinical program, a global phase III test of its immunotherapy candidate Multikine (leukocyte interleukin injection) in advanced primary head and neck cancer. The 928-patient study had been in limbo ever since the agency expressed concerns about matters of risk communication and trial design in late 2016.

Multikine, a patented defined mixture of 14 human natural cytokines, is the company's key asset and one on which it has spent over 10 years and more than $80 million in development and manufacturing validation. It is designed to be administered locally to treat local tumors before any other therapy has been administered.

"We felt that when it comes to cancer immunotherapy, it seems logical that the time when you can have the greatest impact on someone's survival is if you boost their immune system while it is still competent," Cel-Sci CEO and Director Geert Kersten, told BioWorld. "You don't want to reorganize your army after it has already been defeated," he said.

The phase III study, in which all patients in the treatment arm have already received three weeks of Multikine injections prior to standard-of-care surgery, radiation, and/or chemotherapy, can now continue.

For its primary endpoint to be met, it will need to demonstrate that participants treated with Multikine, as well as low dose cyclophosphamide, indomethacin and zinc-multivitamins – all of which are thought to enhance Multikine's activity – plus standard of care provide a 10 percent overall survival advantage vs. standard of care alone. To determine that, it will need to wait for 298 deaths to occur between both arms of the study.

Though efforts by the Vienna, Va.-based company to resolve the partial hold began soon after receipt of its notice, it wasn't until June that it was finally able to satisfy every last request the agency made, an end met in large part by filing a comprehensive submission detailing its belief that it had taken the steps necessary to address the specific deficiencies identified by the agency, including:

• • demonstrating that patients enrolled in the study are not exposed to unreasonable and significant risk of illness or injury;
• • demonstrating that continued enrollment of patients in the study does not expose the patients to unreasonable risks and that the study should not be terminated for futility;
• • demonstrating that a supplemented investigator brochure is not misleading, erroneous, or materially incomplete;
• • demonstrating that the proposed revised clinical protocol is adequate in design to meet the trial's objectives.

Though the hold is lifted, the company remains locked it arbitration with its former clinical research organization, Inventiv Clinical LLC, formerly known as Pharmanet LLC and Pharmanet GmbH. Cel-Sci is seeking damages related to Inventiv's prior involvement in the phase III trial related to claim of breach of contract and fraud. Currently, the company is seeking at least $50 million in damages.

With news that the phase III trial could resume, company shares (NYSE MKT:CVM) rose 70 cents, or 30.4 percent, to close at $3 on Monday.