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PURPOSE We present 5-year results from CheckMate 227 Part 1, in which nivolumab plus ipilimumab improved overall survival (OS) versus chemotherapy in patients with metastatic non–small-cell lung cancer, regardless of tumor programmed death ligand 1 (PD-L1) status. METHODS Adults with stage IV/recurrent non–small-cell lung cancer without EGFR mutations or ALK alterations and with tumor PD-L1 ≥ 1% or < 1% (n = 1739) were randomly assigned. Patients with tumor PD-L1 ≥ 1% were randomly assigned to first-line nivolumab plus ipilimumab, nivolumab alone, or chemotherapy. Patients with tumor PD-L1 < 1% were randomly assigned to nivolumab plus ipilimumab, nivolumab plus chemotherapy, or chemotherapy. End points included exploratory 5-year results for efficacy, safety, and quality of life. RESULTS At a minimum follow-up of 61.3 months, 5-year OS rates were 24% versus 14% for nivolumab plus ipilimumab versus chemotherapy (PD-L1 ≥ 1%) and 19% versus 7% (PD-L1 < 1%). The median duration of response was 24.5 versus 6.7 months (PD-L1 ≥ 1%) and 19.4 versus 4.8 months (PD-L1 < 1%). Among patients surviving 5 years, 66% (PD-L1 ≥ 1%) and 64% (PD-L1 < 1%) were off nivolumab plus ipilimumab without initiating subsequent systemic anticancer treatment by the 5-year time point. Survival benefit continued after nivolumab plus ipilimumab discontinuation because of treatment-related adverse events, with a 5-year OS rate of 39% (combined PD-L1 ≥ 1% and < 1% populations). Quality of life in 5-year survivors treated with nivolumab plus ipilimumab was similar to that in the general US population through the 5-year follow-up. No new safety signals were observed. CONCLUSION With all patients off immunotherapy treatment for ≥ 3 years, nivolumab plus ipilimumab increased 5-year survivorship versus chemotherapy, including long-term, durable clinical benefit regardless of tumor PD-L1 expression. These data support nivolumab plus ipilimumab as an effective first-line treatment for patients with metastatic non–small-cell lung cancer. [Media: see text]

Background: In the global, randomized phase 3 CheckMate 816 study (NCT02998528), neoadjuvant NIVO + chemo demonstrated statistically significant and clinically meaningful improvements in event-free survival (EFS) and pathologic complete response (pCR) vs chemo in pts with resectable NSCLC. Here, we report results from the Chinese subgroup of this study. Methods: Adults with stage IB (≥ 4 cm)-IIIA (per AJCC 7th edition) resectable NSCLC, ECOG PS ≤ 1, and no known EGFR/ALK mutations were randomized to NIVO 360 mg + chemo Q3W or chemo Q3W for 3 cycles followed by surgery. EFS and pCR (per blinded independent review) were primary endpoints; major pathologic response (MPR) and time to death or distant metastasis (TTDM) were secondary endpoints. Presented results are from an updated analysis of EFS (DBL, Oct 14, 2022), and the final analysis of pCR (DBL, Sep 16, 2020). Results: The Chinese subgroup comprised 97 pts (NIVO + chemo, 44; chemo, 53). Baseline characteristics were generally balanced between treatment (tx) arms, except for a higher proportion of pts with stage IIIA NSCLC in the chemo arm. At 38.2 mo’s minimum follow-up, NIVO + chemo improved EFS vs chemo (HR, 0.47; 95% CI, 0.25-0.88). The pCR rate (95% CI) was higher with NIVO + chemo (25.0% [13.2-40.3]) vs chemo (1.9% [0.0-10.1]); MPR and TTDM also favored NIVO + chemo (table). Overall, 36 (81.8%) and 41 (77.4%) pts in the NIVO + chemo and chemo arms, respectively, had definitive surgery. Grade 3-4 tx-related and surgery-related adverse events occurred in 18 (41.9%) and 5 (13.9%) pts in the NIVO + chemo arm, respectively, vs 22 (41.5%) and 9 (22.0%) in the chemo arm. Conclusions: Consistent with results in the global population of CheckMate 816, neoadjuvant NIVO + chemo improved EFS and pCR vs chemo in Chinese pts. The addition of NIVO to neoadjuvant chemo maintained tx tolerability and did not impact the feasibility of surgery. These results support neoadjuvant NIVO + chemo as a tx option for Chinese pts with resectable NSCLC. NIVO + chemo (n = 44) Chemo (n = 53) Median EFS (95% CI), mo NR (23.4-NR) 13.9 (8.3-34.3) HR (95% CI) 0.47 (0.25-0.88) 3-year EFS rate (95% CI), % 58.7 (40.6-73.0) 35.4 (21.8-49.2) pCR rate (95% CI), % 25.0 (13.2-40.3) 1.9 (0.0-10.1) Differencea (95% CI), % 20.9 (7.7-34.1) Odds ratio (95% CI) 11.05 (1.41-86.49) MPR rate (95% CI), % 34.1 (20.5-49.9) 7.5 (2.1-18.2) Differencea (95% CI), % 28.1 (11.9-44.3) Odds ratio (95% CI) 7.42 (1.92-28.65) Median TTDM (95% CI), mo NR (NR-NR) 28.8 (14.8-46.8) HR (95% CI) 0.27 (0.12-0.60) aCalculated using the stratified Cochran-Mantel-Haenszel method. NR, not reached. Citation Format: Changli Wang, Ke-Neng Chen, Qixun Chen, Lin Wu, Qun Wang, Xiaofei Li, Kejing Ying, Wenxiang Wang, Jian Zhao, Lunxu Liu, Junke Fu, Chunfang Zhang, Jichun Liu, Yi Hu, Mark M. Awad, Ives Ntambwe, Junliang Cai, Judith Bushong, Phuong Tran, Shun Lu. Neoadjuvant nivolumab (NIVO) + chemotherapy (chemo) vs chemo in Chinese patients (pts) with resectable NSCLC in CheckMate 816 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT081.

[Introduction] In CheckMate 227, nivolumab plus ipilimumab prolonged overall survival (OS) versus chemotherapy in patients with tumor programmed death-ligand 1 (PD-L1) greater than or equal to 1% (primary end point) or less than 1% (prespecified descriptive analysis). We report results with minimum 4 years' follow-up., [Methods] Adults with previously untreated stage IV or recurrent NSCLC were randomized (1:1:1) to nivolumab plus ipilimumab, nivolumab, or chemotherapy (PD-L1 ≥1%); or to nivolumab plus ipilimumab, nivolumab plus chemotherapy, or chemotherapy (PD-L1, [Results] After 54.8 months' median follow-up, OS remained longer with nivolumab plus ipilimumab versus chemotherapy in patients with PD-L1 greater than or equal to 1% (hazard ratio = 0.76; 95% confidence interval: 0.65–0.90) and PD-L1 less than 1% (0.64; 0.51–0.81); 4-year OS rate with nivolumab plus ipilimumab versus chemotherapy was 29% versus 18% (PD-L1 ≥1%); and 24% versus 10% (PD-L1, [Conclusions] At more than 4 years' minimum follow-up, with all patients off immunotherapy treatment for at least 2 years, first-line nivolumab plus ipilimumab continued to demonstrate durable long-term efficacy in patients with advanced NSCLC. No new safety signals were identified. Immune-mediated AEs occurred early and resolved quickly with guideline-based management. Discontinuation of nivolumab plus ipilimumab due to TRAEs did not have a negative impact on the long-term benefits seen in all randomized patients., This study was supported by Bristol Myers Squibb and Ono Pharmaceutical Company Ltd.

LBA9025 Background: In CheckMate 227 part 1 (NCT02477826), 1L NIVO + IPI demonstrated long-term, durable survival benefit vs platinum-doublet chemo in patients (pts) with metastatic NSCLC regardless of tumor programmed death ligand 1 (PD-L1) expression level. Here we present the longest reported follow-up (5 y) of a phase 3 trial of 1L combination immunotherapy in metastatic NSCLC. Methods: Adults with previously untreated stage IV or recurrent NSCLC, no known EGFR/ ALK alterations , and an ECOG performance status ≤ 1 were enrolled and stratified by histology. Pts with tumor PD-L1 ≥ 1% were randomized 1:1:1 to NIVO (3 mg/kg Q2W) + IPI (1 mg/kg Q6W), NIVO (240 mg Q2W), or chemo. Pts with tumor PD-L1 < 1% were randomized 1:1:1 to NIVO + IPI, NIVO (360 mg Q3W) + chemo, or chemo. Pts were treated until progression, toxicity, or ≤ 2 y for immunotherapy. Assessments included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), duration of response (DOR), and a novel efficacy endpoint, treatment-free interval. Treatment-free interval was measured in pts who discontinued study therapy (for any reason including treatment completion) and was defined as the time from last study dose to start of subsequent systemic therapy or death, whichever occurred first. Results: Minimum follow-up was 61.3 mo (database lock, Feb 15, 2022). In pts with tumor PD-L1 ≥ 1% (N = 1189), continued long-term OS benefit was seen with NIVO + IPI vs chemo (HR, 0.77 [95% CI, 0.66–0.91]); 5-y OS rates were 24% (NIVO + IPI), 17% (NIVO), and 14% (chemo). OS benefit also continued in pts with tumor PD-L1 < 1% (N = 550) for NIVO + IPI vs chemo (HR, 0.65 [95% CI, 0.52–0.81]); 5-y OS rates were 19% (NIVO + IPI), 10% (NIVO + chemo), and 7% (chemo). Clinical benefit with NIVO + IPI vs chemo was observed across additional efficacy endpoints in the overall population and in pts alive at 5 y (table). PFS, ORR, and DOR with NIVO and NIVO + chemo will be presented. Among pts alive at 5 y in the NIVO + IPI group, 66% (PD-L1 ≥ 1%) and 64% (PD-L1 < 1%) remained treatment-free ≥ 3 y after discontinuing study therapy; median (range) duration of NIVO ± IPI therapy was 17.7 (0-25.5) mo (PD-L1 ≥ 1%) and 9.5 (0-25.1) mo (PD-L1 < 1%). No new safety signals were observed. Conclusions: With a 5-y minimum follow-up, NIVO + IPI continues to provide long-term, durable clinical benefit vs chemo in previously untreated pts with metastatic NSCLC, regardless of PD-L1 expression. NIVO + IPI led to increased 5-y survivorship; the majority of these pts were treatment-free for ≥ 3 y post-treatment discontinuation. Clinical trial information: NCT02477826. [Table: see text]

LBA8511 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. [Table: see text]

9016 Background: 1L NIVO + IPI was shown to provide durable long-term overall survival (OS) benefit vs chemo regardless of tumor programmed death ligand 1 (PD-L1) expression in patients (pts) with advanced NSCLC in CheckMate 227 Part 1 (NCT02477826); 3-year OS rates were 33% vs 22% in pts with PD-L1 ≥ 1% (HR, 0.79 [95% CI, 0.67–0.93]) and 34% vs 15% in pts with PD-L1 < 1% (HR, 0.64 [95% CI, 0.51–0.81]). Here we report updated results from the study with 4 years’ minimum follow-up. Methods: Adults with previously untreated stage IV / recurrent NSCLC, no known EGFR/ ALK alterations , and ECOG performance status ≤ 1 were enrolled; pts were stratified by squamous (SQ) and non-squamous (NSQ) histology. Pts with PD-L1 ≥ 1% (n = 1189) were randomized 1:1:1 to receive NIVO (3 mg/kg Q2W) + IPI (1 mg/kg Q6W), NIVO alone (240 mg Q2W), or chemo. Pts with PD-L1 < 1% (n = 550) were randomized 1:1:1 to receive NIVO + IPI, NIVO (360 mg Q3W) + chemo, or chemo. OS with NIVO + IPI vs chemo in pts with PD-L1 ≥ 1% was the primary endpoint. Results: With minimum follow-up of 49.4 months (database lock, Feb 18, 2021), pts were at least 2 years beyond the protocol-specified end of immunotherapy treatment. Pts with PD-L1 ≥ 1% continued to show durable benefit with NIVO + IPI vs chemo (HR, 0.76 [95% CI, 0.65–0.90]); 4-year OS rates were 29% (NIVO + IPI), 21% (NIVO), and 18% (chemo). At 4 years, 14% (NIVO + IPI), 10% (NIVO), and 4% (chemo) remained progression free. Among responders, 34%, 30%, and 7% remained in response, respectively. In an exploratory analysis in pts with PD-L1 ≥ 50%, 4-year OS rates were 37% (NIVO + IPI), 26% (NIVO), and 20% (chemo). In pts with PD-L1 < 1%, OS HR for NIVO + IPI vs chemo was 0.64 (95% CI, 0.51–0.81); 4-year OS rates were 24% (NIVO + IPI), 13% (NIVO + chemo) and 10% (chemo). At 4 years, 12% (NIVO + IPI), 7% (NIVO + chemo), and 0% (chemo) remained progression free. Among responders, 31%, 13%, and 0% remained in response, respectively. Among pts who progressed on NIVO + IPI vs chemo, 7% vs 40% (PD-L1 ≥ 1%), and 9% vs 33% (PD-L1 < 1%), received subsequent immunotherapy. Benefit with NIVO + IPI vs chemo was observed for both SQ and NSQ histology (Table). With long-term follow-up, no new safety signals were identified. Conclusions: With 4 years’ minimum follow-up, 1L NIVO + IPI continued to provide durable, long-term OS benefit vs chemo in pts with advanced NSCLC regardless of PD-L1 expression or histology. Clinical trial information: NCT02477826. [Table: see text]