CEL-SCI’s Phase 3 clinical trial assessing its investigational drug Multikine in patients with squamous cell carcinoma of the head and neck (SCCHN) recently was placed on partial clinical hold by the U.S. Food and Drug Administration. Now the company has submitted its response to the FDA, hoping the agency will lift the partial clinical hold and resume patient enrollment, according to a press release.

Multikine (Leukocyte Interleukin, Injection), CEL-SCI‘s lead investigational therapy, is being developed for the potential treatment of head and neck cancer, peri-anal warts, or cervical dysplasia (a precancerous condition) in patients co-infected with both human immunodeficiency virus (HIV) and human papillomavirus (HPV). It is a defined mix of small proteins, called cytokines, known to induce strong immune responses, being able to activate both passive and active immunity.

CEL-SCI is first pursuing Multikine approval as an neoadjuvant therapy for SCCHN patients. The reasoning for its administration prior to surgery, radiation or chemotherapy lies on the generally accepted hypothesis that this represents the period when anti-tumor immune response has the potential to be more fully activated.

The global Phase 3 trial (NCT01265849) was designed to assess the safety and efficacy of Multikine plus  standard of care therapy (surgery followed by radiotherapy or concurrent radiochemotherapy) versus standard of care alone in 880 patients with advanced primary SCCHN. The study’s primary outcome was overall survival, and secondary outcomes included progression-free survival, local regional control and quality of life.

According to the company website, on Aug. 31, 2016, CEL-SCI announced the accumulation of deaths in the study was lower than anticipated, meaning the study would take longer than expected to complete.

To minimize this, CEL-SCI decided to extend the study up to 1,273 patients to have 1,146 evaluable patients, which would allow the study to be completed in a more timely manner. As required by law, the company submitted an amendment to the existing Phase 3 protocol to the regulatory agencies in the countries where the Phase 3 trial is being conducted.

However, the protocol amendment and the Phase 3 study were placed on partial clinical hold by the FDA, pausing patient enrollment. Patients already in the study continued receiving Multikine as planned.

Now, CEL-SCI is working to persuade the FDA to lift the partial clinical hold and resume enrollment.

Given that Multikine has been granted orphan drug status, this Phase 3 trial may be sufficient to have the drug approved for advanced primary SCCHN patients who have not received any other treatments.

Additional clinical indications for Multikine also are being investigated. A Phase 1 trial assessing Multikine in HIV/HPV co-infected women with cervical dysplasia has been completed at the University of Maryland, showing promising efficacy results with a tolerable safety profile.