Adding Novel Inhaled Agent May Improve Lung Cancer Outcomes

Delivery of cytokines to the lungs via a novel inhaled vector platform, along with an immune checkpoint inhibitor (ICI), may potentially both enhance anti-tumor activity and potentially overcome ICI resistance in people with advanced non-small cell lung cancer (NSCLC).

The novel investigational immunotherapy KB707 is made from a non-replicating herpes simplex virus type 1-based vector that encodes human interleukin-12 (IL-12) and interleukin 2 (IL-2). Delivery via inhalation allows for high doses of the two cytokines to reach the local tumor environment in the lungs.

“When delivered intravenously, both IL-2 and IL-12 can cause severe side effects like cytokine release syndrome. This particular clinical trial is looking at delivery by inhalation. We hope that by confining the cytokines to the lungs, we can avoid the systemic side effects,” says lead investigator Wen Wee Ma, MD, of Cleveland Clinic Cancer Institute.

The new phase 1/2 findings are the latest from Ma’s oncology team. Last year, they demonstrated anti-tumor effects and safety using KB707 as monotherapy in patients with NSCLC who had been heavily treated. Now, they’ve achieved similarly encouraging results using KB707 in combination with the ICI pembrolizumab.

Dr. Ma presented the new findings at the annual meeting of the American Society of Clinical Oncology (ASCO).

A total of 21 patients with stage 3 or 4 NSCLC have been enrolled in the trial since January 1, 2026. All had previously received one prior line of ICI, with or without platinum-based chemotherapy, but had stopped due either to lack of efficacy or tolerability. The study protocol involved receiving nebulized KB707 (10⁹ plaque-forming units) in combination with 400mg pembrolizumab every six weeks.

Of 16 participants evaluated for efficacy, five achieved a partial response, resulting in an overall response rate of 31.3%. Another seven patients maintained stable disease, while four experienced disease progression. The response was durable. All patients remained alive as of the study cutoff date. Neither median duration of response nor progression-free survival endpoints had been reached at the time of evaluation.

Safety was evaluated in all 21 patients. A total of 14 patients (66.7%) experienced one or more treatment-related adverse events, including:

• Dyspnea (33.3%)
• Vomiting (14.3%)
• Cough, chills, fatigue, influenza-like illness or pyrexia (9.5% each)

Most side effects were grade 1 or 2 and transient. One individual experienced grade 1 cytokine release syndrome.

“This is a phase 1 study, where we’re looking at treatment in early testing and the goal is to figure out whether it is worth going forward. We achieved our aims regarding both safety and efficacy. All of the patients had stopped responding to prior treatment that included ICI. We achieved a response rate approximately30% when we added KB707 to an ICI. It’s very encouraging to see that,” Dr. Ma notes.

The study is proceeding. At the same time, a new cohort with advanced NSCLC is enrolling patients to further evaluate inhaled KB707 in combination with the standard chemotherapy agent docetaxel.

Future plans include investigating whether KB707 might help induce a response to pembrolizumab in people whose tumors don’t respond to it initially.

Another future research avenue will explore whether KB707 can induce an “abscopal effect,” or activation and circulation of immune cells outside the targeted treatment area in the lung. This activation could potentially treat cancers in other parts of the body such as the liver or pancreas. “In phase 1 we cannot make big conclusions, but it's definitely a glimpse of the future,” Dr. Ma says.

In February 2026, the US Food and Drug Administration granted KB707 Regenerative Medicine Advanced Therapy designation, intended to support and expedite the development of regenerative medicine therapies. Prior to that, in February 2024, FDA had granted it Fast Track Approval Designation.