New Inhalable Agent Could Improve Treatment Outcomes in Lung Cancer

A new viral-based vector that can be inhaled into the lungs could boost the anti-cancer response of the body in patients diagnosed with advanced lung cancer. This new treatment could also restore sensitivity to immune checkpoint inhibitors among patients that had become unresponsive. 

The new investigational therapy, dubbed KB707, was developed by a team at Cleveland Clinic Cancer Institute. The treatment is based on a vector platform leveraging a modified herpes simplex virus that is non-replicating. The agent delivers cytokines IL-12 and IL-2 directly into the lungs once the patient inhales it. 

This delivery via inhalation helps to get the therapy into the microenvironment of the tumors in the lungs, and the non-replicating nature of the modified virus vector prevents the treatment from triggering a cytokine storm that could be potentially life-threatening. 

Previous attempts to deliver this agent using an infusion into the bloodstream had resulted in systemic adverse reactions due to the cytokine storm, and switching to the inhalable version was a way to avoid those systemic adverse events. Doctor Wen Wee Ma, the lead investigator of the study, explains that the inhalable agent makes it possible to deliver high doses of the needed cytokines that can trigger a strong anti-tumor response in patients. 

This latest Phase 1/2 trial involved 21 non-small cell lung cancer patients who had become unresponsive or couldn’t tolerate the immune checkpoint inhibitor therapy that had been prescribed by their oncologists. 

The study participants were given inhalable KB707 together with the ICI pembrolizumab every six weeks. The combination therapy triggered a partial response in 31.3% (5 individuals) of the participants while seven subjects had their cancer remain stable during the study period. Four of the subjects seemed unresponsive and their cancer progressed during the treatment period. This evaluation covered just 16 of the subjects and the others dropped out. 

The study subjects were also evaluated for any adverse events related to this new treatment and the side effects were generally transient and low-grade. These side effects included vomiting in 14.3% of the subjects, dyspnea in 33.3% of the patients, and 9.5% experienced either fatigue, chills, cough, pyrexia or influenza-like symptoms. 

Dr. Ma said their interest in conducting this Phase 1 study was to find out whether it was worthwhile to continue with other steps of developing and testing the novel agent, and their findings were encouraging. They are particularly happy that the inhalable agent was able to trigger a response in patients that had become unresponsive to immune checkpoint inhibitor therapy. 

These positive results build on the progress that is being made elsewhere by entities like Calidi Biotherapeutics Inc. (NYSE American: CLDI) that are also exploring mechanisms to use modified viruses as vehicles to deliver genetic payloads that can help the body fight against cancer. 

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