Phase I NK510-PD-1 combination shows preliminary safety in nine lung cancer patients

A first-in-human phase I clinical trial found no dose-limiting toxicities when TIGIT-disrupted NK510 was combined with PD-1 blockade in nine patients with advanced non-small cell lung cancer who had previously received PD-1-targeted treatment. Weekly NK510 infusions were tested at three dose levels, including a highest dose of 12 × 10^9 cells, and the regimen was generally well tolerated. Preliminary efficacy measurements were reported, but the small study cannot establish whether adding NK510 improved outcomes.

The open-label, single-center study used a conventional 3 + 3 dose-escalation design. Participants received NK510 at 6 × 10^9, 9 × 10^9, or 12 × 10^9 cells in six consecutive weekly infusions, together with the same PD-1 inhibitor used before enrollment. NK510 is an allogeneic natural killer-cell product created using base editing to disrupt TIGIT. The product was designed to enhance natural killer-cell activation in the tumor microenvironment. The primary endpoint was safety, including assessment of dose-limiting toxicities. Secondary endpoints were objective response rate, disease control rate, progression-free survival, and duration of response.

Among the nine treated patients, the objective response rate was 11.1%, with a 95% confidence interval of 0.3–48.2%. The disease control rate was 66.7%, with a 95% confidence interval of 29.9–92.5%. Median progression-free survival was estimated at 8.6 months, with a 95% confidence interval of 1.53 months to not reached. These estimates have substantial uncertainty because they were based on only nine participants. The results describe observations from this early phase I cohort and do not demonstrate that NK510 increased response, disease control, or progression-free survival relative to PD-1 blockade alone.

Fever and chills were the most common treatment-related adverse events. The investigators reported no unexpected safety signals and no grade 3 or higher immune-related adverse events. Exploratory cytokine analyses showed variable changes across patients and sampling time points, providing preliminary biological observations rather than evidence of a consistent mechanism. Overall, the findings support the feasibility and preliminary tolerability of TIGIT-disrupted NK510 combined with PD-1 blockade at the doses evaluated. The limited sample size restricts the ability to characterize uncommon adverse events, compare dose levels reliably, or assess antitumor activity with precision.

The study enrolled a narrowly defined population: patients with advanced, PD-1-pretreated non-small cell lung cancer, specifically described in the study background as including patients without actionable driver alterations. Its single-center design, first-in-human dose-escalation format, and enrollment of only nine patients make the results suitable primarily for evaluating initial safety and feasibility. The authors concluded that the preliminary disease-control signal warrants further investigation in larger prospective trials. Whether NK510 provides a measurable clinical benefit, which doses should be carried forward, and how the combination performs in broader populations remain unresolved by these data.

Subject of Research: Phase I evaluation of TIGIT-disrupted NK510 combined with PD-1 blockade in advanced non-small cell lung cancer

Article Title: A phase I clinical trial of NK510 combined with PD-1 blockade in patients with advanced non-small cell lung cancer

Article References: Cheng, J., Cheng, Q., Zhu, S., Mei, Y., Yang, F., Zhan, P., Xu, T., Yan, J., Song, X., Zhang, J., Han, H., Yuan, D., Yao, Y., & Lv, T. (2026). A phase I clinical trial of NK510 combined with PD-1 blockade in patients with advanced non-small cell lung cancer. Cancer Immunology, Immunotherapy. https://doi.org/10.1007/s00262-026-04604-8

Image Credits: AI Generated

DOI: 10.1007/s00262-026-04604-8

Keywords: NK510, natural killer cells, TIGIT, PD-1 blockade, non-small cell lung cancer, phase I trial, dose escalation, cancer immunotherapy, treatment safety, tumor microenvironment, phase, clinical