Inhaled delivery of KB707, a novel HSV-based immunotherapy, in combination with pembrolizumab in advanced non–small cell lung cancer: A phase 1/2 study.

Abstract

8564 Background: Though immune checkpoint inhibitors (ICIs) have significantly improved the treatment for lung cancers, resistance invariably develops and novel approaches are needed to overcome such resistance and enhance anti-tumor immunity. KB707 is a replication-defective herpes simplex virus type 1 (HSV-1)-based vector engineered to deliver human interleukin (IL)-12 and IL-2 to induce both innate and adaptive antitumor immunity. Inhaled KB707 monotherapy was previously shown to be well tolerated with encouraging efficacy in pts with advanced non-small cell lung cancer (aNSCLC): 4 of 11 pts achieved partial response (PR). Delivery of IL-12/IL-2 by inhaled KB707 may significantly increase the anti-tumor efficacy of ICI (pembro) in pts with aNSCLC who are relapsed or refractory to standard therapy. Extending from the monotherapy results, the safety and efficacy of adding inhaled KB707 to pembro in pts with aNSCLC is presented. Methods: KB707-02 is a Phase 1/2, open-label, multicenter study of inhaled KB707 (NCT06228326). Eligible pts with at least one measurable lung lesion at screening and histological confirmation of stage 3 or 4 NSCLC received nebulized KB707 (10 9 PFU) every 2 weeks and pembro (400 mg) every 6 weeks. Pts must have previously received one line of prior ICI, with or without platinum-based chemotherapy. The primary objective is to assess safety and tolerability per CTCAE v5.0, with a secondary objective to evaluate preliminary efficacy per RECIST 1.1. Results: As of 01 Jan 2026, a total of 21 pts (11 female) were enrolled and received at least one dose of inhaled KB707 plus pembro. The majority of treatment-related adverse events (TRAE) have been mild to moderate in severity and transient. Consistent with known adverse event profiles of IL-2 and IL-12, the most common TRAE were flu-like symptoms (fever, chills, vomiting, fatigue) and dyspnea. The efficacy population (n=16) received at least one treatment cycle and had at least one evaluation per RECIST 1.1. The 16 pts were of advanced age (median 72 [50-88] years old) and heavily treated (3 median lines of prior therapies). The ORR was 31.3% (5/16) and DCR was 75% (12/16) with 5 pts achieving confirmed PR and 7 with stable disease (SD). Median treatment duration was 24.1 weeks (6.1-71.9) with 5 out of 16 pts remaining on study. Median overall survival and progression free survival were not reached. Conclusions: Delivery of IL-12/IL-2 by inhaled KB707 in combination with pembro was well tolerated and encouraging antitumor effects were observed in heavily treated aNSCLC, as evidenced by 31.3% ORR and 75% DCR. The study is proceeding with enrollment of an additional cohort to further evaluate inhaled KB707 in combination with docetaxel in aNSCLC. Clinical trial information: NCT06228326 .