FDA Grants RMAT Designation to Inhalable Gene Therapy for Advanced Lung Tumors

The US FDA has granted regenerative medicine advanced therapy (RMAT) designation to KB707, an investigational, inhaled gene therapy, for the treatment of patients with locally advanced or metastatic solid tumors of the lung that have progressed on standard-of-care therapy.¹ This regulatory milestone is based on preliminary clinical data suggesting the therapy’s potential to address significant unmet needs in the refractory lung cancer population.

The RMAT designation was established under the 21st Century Cures Act to expedite the development and review of regenerative medicine therapies intended to treat serious or life-threatening conditions.² To qualify, a therapy must demonstrate preliminary clinical evidence of the potential to address an unmet medical need. This designation provides the benefits of fast track and breakthrough therapy designations, including intensive FDA guidance on efficient drug development and eligibility for priority review and accelerated approval.

“The FDA’s decision to grant RMAT designation to KB707 reflects both the urgent unmet need for new [non–small cell lung cancer (NSCLC)] therapies as well as the promising early clinical evidence of efficacy we have observed with inhaled KB707 in patients with advanced NSCLC,” said Suma Krishnan, president of Research and Development at Krystal Biotech, in a news release.¹ “This is the second RMAT designation granted to a Krystal program and, as such, we know first-hand the benefits that this designation can provide to accelerate development and shorten the path to a potential approval. We are excited to work closely with the FDA to maximize the potential impact of our KB707 program for patients with NSCLC.”

Mechanistic Overview: Redosable Gene Therapy

KB707 represents a shift in cytokine-based immunotherapy. While interleukin-12 (IL-12) and interleukin-2 (IL-2) are recognized as potent mediators of antitumor immunity, their clinical utility has historically been limited by severe systemic toxicities, such as vascular leak syndrome and cytokine storm, when administered intravenously.³

KB707 utilizes a proprietary, modified herpes simplex virus type 1 (HSV-1) vector to deliver functional human IL-12 and IL-2 directly to the tumor microenvironment. The vector is engineered to be nonreplicating and nonintegrating, minimizing the risk of insertional mutagenesis. By utilizing a nebulized delivery system, the therapy is inhaled, allowing for localized expression of cytokines within the lungs. This approach seeks to induce both a local immune response and a systemic abscopal effect while maintaining a favorable safety profile by limiting systemic exposure.¹

Clinical Evidence from the KYANITE-1 Study

The FDA’s decision was supported by interim results from the ongoing phase 1/2 KYANITE-1 study (NCT06228326).⁴ This open-label, dose-escalation study is evaluating the safety, tolerability, and efficacy of inhaled KB707 in patients with advanced solid tumors involving the lungs.

Data were presented at the 2025 ASCO Annual Meeting.³ As of the data cutoff of January 8, 2025, the maximum tolerated dose was not reached, and the adverse event (AE) profile was consistent with the known profiles of IL-2 and IL-12. Most treatment-related AEs were transient and mild to moderate in severity, with no grade 4 or 5 AEs reported. Of 11 response-evaluable patients, the overall response rate was 27% (n = 3), and the disease control rate was 73% (n = 8), with 7 of 11 patients remaining on study. The response rate of target lesions in the lungs was 36%. The median duration of response was not yet reached, with treatment durations ranging from 10.3 to 33.3 weeks. The median patient age was 71 (range, 54-77), and the population was heavily pretreated, with a median of 4 prior lines of therapy. All patients previously received at least 1 line of immunotherapy.

REFERENCES

1. Krystal Biotech announces RMAT designation granted by FDA to KB707 for the treatment of advanced or metastatic non-small cell lung cancer. News release. Krystal Biotech. February 9, 2026. Accessed February 11, 2026. https://tinyurl.com/3y25shz4

2. Regenerative Medicine Advanced Therapy Designation. US FDA. Updated November 4, 2025. Accessed February 11, 2026. https://tinyurl.com/mr2x3hca

3. Ma WW, McKean M, Villaruz LC, 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

4. A study assessing KB707 for the treatment of advanced solid tumor malignancies affecting the lungs (KYANITE-1). ClinicalTrials.gov. Updated October 24, 2025. Accessed February 11, 2026. https://clinicaltrials.gov/study/NCT06228326