KB707 (inhaled HSV-1 IL-12/IL-2 immunotherapy) + pembrolizumab drives 31% ORR in ICI-experienced aNSCLC

KB707 is a replication-defective HSV-1 vector engineered to deliver intratumoral IL-12 and IL-2 via inhalation, aiming to re-inflame the lung tumor microenvironment and deepen PD-1 blockade responses; here it was combined with pembrolizumab in KB707-02, an open-label Phase 1/2 multicenter study (NCT06228326) in stage III/IV aNSCLC after ≥1 prior ICI line (KB707 10^9 PFU q2w + pembrolizumab 400mg q6w). As of January 1, 2026, 21 patients were treated; in the efficacy-evaluable set (n=16; median age 72; median 3 prior lines), ORR was 31.3% (5/16 confirmed PR) and DCR 75% (12/16), with median treatment duration 24.1 weeks and median PFS/OS not reached. TRAEs were mostly mild–moderate and transient, dominated by expected IL-2/IL-12-type flu-like symptoms and dyspnea; efficacy looks numerically above typical single-agent docetaxel benchmarks in previously treated NSCLC (ORR ~10%–15%, mPFS ~3 months) and even above docetaxel+ramucirumab in REVEL (ORR 22.9%, mPFS 4.5 months, mOS 10.5 months), albeit with far less mature follow-up and a much smaller dataset.