In February, the US Food and Drug Administration (FDA) granted Regenerative Medicine Advanced Therapy (RMAT) designation to KB707, an experimental gene therapy administered via inhalation to the lungs, for the treatment of advanced or metastatic non-small cell lung cancer (NSCLC). KB707 uses a replication-defective herpes simplex virus type 1 (HSV-1)-based vector to deliver high doses of immune-stimulating cytokines to the local tumor environment.1
RMAT designation is a specialized FDA program designed to expedite the review and development of regenerative medicines intended to treat serious unmet medical needs, including cell and gene therapies. The FDA granted this designation based on results from the phase I/II KYANITE-1 open-label, multicenter, dose-escalation trial, which found that KB707 was generally safe and well tolerated when administered via inhalation, with observed single-agent antitumor activity.1
Eligibility criteria include a histologically confirmed diagnosis of advanced solid tumor malignancy in the lungs and at least one measurable lung lesion identified during screening.1 Enrolled participants received a weekly nebulized dosing schedule of KB707 for up to 3 weeks, followed by maintenance treatment every 3 weeks.1
Safety and tolerability were the primary endpoints, while preliminary efficacy and the incidence of dose-limiting toxicities were secondary endpoints.2 Among the 11 response-evaluable patients with NSCLC—including those of advanced age (median: 71 years) and heavily pretreated (median of four prior lines of therapy; all had received at least one prior line of immunotherapy)—the findings indicated that most treatment-related adverse events were mild to moderate in severity, and a maximum tolerated dose was not reached.1
The results showed an overall response rate of 27% and a disease control rate of 73%. Specifically, target lung lesions demonstrated a 36% response rate.1 At the time of analysis, the median duration of response had not yet been reached.1
Overall, investigators reported that inhaled KB707 was generally well tolerated, with antitumor efficacy observed—including in heavily pretreated patients.1 The study has been expanded to evaluate the combination of inhaled KB707 plus pembrolizumab, with or without chemotherapy, in patients with advanced NSCLC, and enrollment is ongoing.1
References:
- 1. Wen Wee Ma et al. Inhaled KB707, a novel HSV-based immunotherapy, as a monotherapy in patients with advanced solid tumor malignancies affecting the lungs: Efficacy and safety results from a phase 1/2 study.. J Clin Oncol 43, 2575-2575(2025). doi:10.1200/JCO.2025.43.16_suppl.2575
- 2. Expedited Programs for Regenerative Medicine Therapies for Serious Conditions
- 3. A Study Assessing KB707 for the Treatment of Advanced Solid Tumor Malignancies Affecting the Lungs (KYANITE-1). NCT06228326
