Forde PM, et al. - Researchers performed a trial of programmed death 1 (PD-1) inhibitor nivolumab in adults with untreated, surgically resectable early (stage I, II, or IIIA) non–small-cell lung cancer (NSCLC), focusing on safety, feasibility as well as effects of nivolumab in this patient population. Neoadjuvant nivolumab was shown to be related to few side effects, did not delay surgery, and induced a major pathological response in 45% of resected tumors. The pathological response to PD-1 blockade was predicted by tumor mutational burden. Furthermore, in peripheral blood, mutation-associated, neoantigen-specific T-cell clones were noted to undergo expansion as a result of treatment.

Methods

• Adults with untreated, surgically resectable early (stage I, II, or IIIA) NSCLC were given two preoperative doses of PD-1 inhibitor nivolumab in this pilot study.
• Every 2 weeks Intravenous administration of nivolumab (at a dose of 3 mg per kilogram of body weight) was carried out, with surgery planned approximately 4 weeks after the first dose.
• Safety and feasibility were primary end points.
• The tumor pathological response, expression of programmed death ligand 1 (PD-L1), mutational burden, and mutation-associated, neoantigen-specific T-cell responses were also assessed.

Results

• With an acceptable side-effect profile, neoadjuvant nivolumab was not associated with delays in surgery.
• Complete resection of 20 of the 21 tumors that were removed, was performed.
• In 9 of 20 resected tumors (45%), a major pathological response occurred.
• Both PD-L1–positive and PD-L1–negative tumors responded.
• A significant correlation was seen between the pathological response and the pretreatment tumor mutational burden.
• In 8 of 9 patients who were assessed, PD-1 blockade caused systemic increase in the number of T-cell clones that were found in both the tumor and peripheral blood.
• At 2 to 4 weeks after treatment, rapid expansion of mutation-associated, neoantigen-specific T-cell clones from a primary tumor with a complete response on pathological assessment, was detected in peripheral blood; some of these clones were not detected before the administration of nivolumab.