Development Program for KB707 Will Prioritize Inhaled Formulation for NSCLC

The development program for the immunotherapy KB707 will prioritize an inhaled formulation of the agent for the treatment of patients with non–small cell lung cancer (NSCLC), according to an announcement from Krystal Biotech.¹

As such, the company announced it was also pausing enrollment of the phase 1/2 OPAL-1 trial (NCT05970497) evaluating intratumoral KB707 in patients with locally advanced or metastatic solid tumor malignancies.

The company was also granted an end of phase 2 meeting with the FDA in October 2025 to further discuss developmental pathways for inhaled KB707.

“The acceleration of our work on inhaled KB707 is a reflection of both the clear and acute unmet need that exists for new treatments of NSCLC and the promising efficacy profile we have observed to date with inhaled KB707,” Suma Krishnan, president of Research and Development of Krystal Biotech, stated in a news release. “We look forward to meeting with the FDA and bringing another urgently needed therapeutic option to patients.”

Data from the phase 1/2 KYANITE-1 trial (NCT06228326) presented at the 2025 ASCO Annual Meeting showed that efficacy-evaluable patients with NSCLC treated with inhaled KB707 (n = 11) achieved an overall response rate (ORR) of 27% as of the abstract data cutoff; patients experienced partial response (PR; n = 3), stable disease (n = 5), or progressive disease (n = 3).² With extended follow-up, the ORR was 36%, with 4 patients achieving a PR.

Regarding safety, any-grade treatment-related adverse effects (TRAEs) were reported in 66.7% of patients, although no grade 4 or 5 TRAEs occurred. The most common any-grade TRAEs comprised chills (25.6%), cytokine release syndrome (CRS; 23.1%), fatigue (20.5%), flu-like illness (15.4%), dyspnea (15.4%), vomiting (12.8%), and pyrexia (10.3%). Notably, the rate of grade 3 CRS was 2.6%.

KB707 Background and KYANITE-1 Overview

The novel gene therapy KB707 is a replication-defective herpes simplex virus type 1–based vector encoding human interleukin (IL)-12 and IL-2. The agent is intended to bring high cytokine doses to the local tumor microenvironment.

In the open-label, dose-escalation and -expansion KYANITE-1 study, investigators enrolled patients with at least 1 measurable lung lesion and a histologically confirmed solid tumor malignancy of the lungs to participate in the KB707 monotherapy portion of the study.

The trial is also enrolling patients with histologically or cytologically confirmed stage III/IV NSCLC to receive KB707 in combination with pembrolizumab (Keytruda) with or without chemotherapy. Notably, eligible patients from the monotherapy cohorts are allowed to roll over to participate in the combination cohorts.

During the monotherapy phase, KB707 was administered at doses ranging from 10⁸ to 10⁹ plaque-forming units (PFU; n = 16). During dose expansion (n = 23), patients received the agent at 10⁹ PFU. The agent was administered on days 1, 8, 15, 36+, and 57+, with tumor evaluation also performed on day 57 or beyond.

Safety, immunologic biomarkers, and preliminary efficacy were the primary objectives for the monotherapy portion of the study.

In the efficacy-evaluable cohort, the median age was 71 years (range, 54-77), and most patients were female (63.6%), had an ECOG performance status of 1 (90.9%), and had stage IV disease (100%). Additionally, 18.2% of patients had a PD-L1 expression of at least 1%, and 45.5% of patients had PD-L1 expression under 1%; PD-L1 status was unknown in 36.4% of patients.

Patients had received a median of 4 prior lines of therapy. Notably, 63.6% of patients had undergone 1 prior line of immunotherapy, and 36.4% of patients had received at least 2 prior lines of immunotherapy.

References

1. Krystal Biotech announces update on development plans for oncology program KB707 and prioritization of inhaled KB707 for the treatment of non-small cell lung cancer. News release. Krystal Biotech. August 21, 2025. Accessed August 22, 2025. https://ir.krystalbio.com/news-releases/news-release-details/krystal-biotech-announces-update-development-plans-oncology
2. Ma WW, McKean M, Villaruz L, 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