FDA Grants RMAT Designation to HSV-Based Immunotherapy in NSCLC

The FDA has granted regenerative medicine advanced therapy (RMAT) designation to KB707, an investigational replication-defective herpes simplex virus type 1 (HSV-1)–based immunotherapy, for patients with advanced or metastatic non–small cell lung cancer (NSCLC), according to a press release from the developer, Krystal Biotech, Inc.¹

Supporting data for the designation came from the phase 1/2 KYANITE-1 trial (NCT06228326), in which KB707 demonstrated meaningful antitumor activity among patients with heavily pretreated advanced NSCLC. Investigators presented findings from the KYANITE-1 trial at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting.²

Among 11 evaluable patients with NSCLC, partial responses (PRs) were observed in 3 at the time of abstract data cutoff and 4 at the time of extended follow-up. Data showed an objective response rate (ORR) of 27% and 36% during each respective period.

Safety findings among 39 patients with solid tumors revealed that treatment-related adverse effects (TRAEs) were typically grade 1 or 2 and transient. Investigators observed no grade 4/5 TRAEs, and 66.7% (n = 26) of patients experienced at least 1 TRAE. The most common TRAEs of any grade included chills (25.6%), cytokine release syndrome (23.1%), fatigue (20.5%), and influenza-like illness (15.4%).

“The FDA’s decision to grant RMAT designation to KB707 reflects both the urgent unmet need for new NSCLC therapies as well as the promising early clinical evidence of efficacy we have observed with inhaled KB707 in patients with advanced NSCLC. 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,” Suma Krishnan, president of Research and Development at Krystal Biotech, stated in the press release.¹ “We are excited to work closely with the FDA to maximize the potential impact of our KB707 program for patients with NSCLC.”

Developers designed KB707 as an HSV-1–based vector encoding human interleukin-12 (IL-12) and IL02. The investigational gene therapy can deliver high doses of cytokines to the local tumor microenvironment.

In the open-label, dose-escalation, and dose-expansion phase 1/2 trial, 16 patients with at least 1 measurable lung lesion at screening were assigned to receive KB707 at 10⁸ to 10⁹ PFU as part of the dose-escalation portion; 23 patients received the agent at 10⁹ PFU during the dose-expansion portion.

The trial also includes a combination therapy cohort, which was enrolling at the time of the presentation at ASCO. Here, patients with histologically or cytologically confirmed stage III or IV NSCLC will receive KB707 plus pembrolizumab (Keytruda) with or without chemotherapy.

The trial’s primary end point was the safety and tolerability of KB707 based on AEs.³ Secondary end points included dose-limiting toxicities and preliminary efficacy based on ORR.

Patients 18 years and older with an ECOG performance status of 0 or 1, at least 1 measurable lesion per RECIST v1.1 criteria, histologically confirmed advanced solid tumor malignancies affecting the lungs, and progression on prior standard-of-care therapy were eligible for enrollment on the trial. Those who had not fully recovered from prior surgery or radiotherapy and patients with HIV-positive status were ineligible for study entry.

The median age was 64 years (range, 20-80) in the solid tumor population and 71 years (range, 54-77) in the NSCLC efficacy evaluable population. In the NSCLC cohort, most patients had an ECOG performance status of 1 (90.9%), stage IV disease (100%), PD-L1–negative disease (45.5%), and 1 line of prior immunotherapy (63.6%).

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, Inc. February 9, 2026. Accessed February 9, 2026. https://tinyurl.com/3y3rn3eb
2. 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. 2025;43(suppl 16):2575. doi:10.1200/JCO.2025.43.16_suppl.2575
3. 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 9, 2026. https://tinyurl.com/4rtdej7a