Background: Several studies have shown an association of pathological response, a common efficacy endpoint in neoadjuvant therapy trials, with survival for chemo in various cancers including resectable NSCLC. However, the association between pathological complete response (pCR) and survival as well as the degree of pathological regression that may be predictive of EFS for neoadjuvant immunotherapy has not been rigorously studied. CheckMate 816 (NCT02998528), a randomized phase 3 study of neoadjuvant NIVO + chemo vs chemo in resectable NSCLC, met both of its primary endpoints with a statistically significant and clinically meaningful improvement in EFS and pCR. Here, we report a post hoc analysis from CheckMate 816, characterizing the association between pathological regression and EFS. Methods: Adults with resectable NSCLC were randomized to NIVO 360 mg + platinum-doublet chemo Q3W or chemo alone Q3W for 3 cycles. Primary endpoints were EFS and pCR (0% residual viable tumor [RVT] in the primary tumor [PT] and lymph nodes [LN] based on immune-related pathological response criteria), both assessed by blinded independent review. Major pathological response (MPR; ≤10% RVT in the PT and LN) was a secondary endpoint. In this post hoc analysis, EFS was assessed based on depth of pathological regression (measured by %RVT) in the PT only. Also, a time-dependent receiver operating characteristic curve analysis assessed the predictive ability of %RVT (PT only) for EFS outcome at 2 years, using area under the curve (AUC) to summarize the overall diagnostic accuracy (0.5 = random chance; 1 = perfect accuracy). Results: Baseline characteristics in patients (pts) with pathologically evaluable samples were well balanced between the NIVO + chemo and chemo arms, similar to the overall population. In both treatment arms, EFS (minimum follow-up, 21 months) was improved in pts with vs without pCR or MPR (Table). %RVT appeared to be predictive of EFS at 2 years for NIVO + chemo (AUC = 0.74) but an association was not clear for chemo (AUC = 0.54). 2-year EFS rates for NIVO + chemo were 90%, 60%, 57%, and 39% for pts with 0–5%, >5–30%, >30–80%, and >80% RVT, respectively. Conclusions: In CheckMate 816, pathological response (pCR and MPR) in the PT was associated with improved EFS with neoadjuvant NIVO + chemo. Additionally, depth of pathological regression appeared to be predictive of improved EFS. Clinical trial information: NCT02998528.

^aHR was NC for the chemo arm due to only 5 pts having a pCR. NC, not computed; NR, not reached.