Perioperative nivolumab (NIVO) vs placebo (PBO) in patients (pts) with resectable NSCLC: Updated survival and biomarker analyses from CheckMate 77T.

LBA8007 Background: In CheckMate 77T, perioperative NIVO showed statistically significant EFS improvement vs neoadjuvant (neoadj) chemo followed by adjuvant (adj) placebo (PBO) in pts with stage (stg) II or III resectable NSCLC. We report clinical outcomes by baseline (BL) stg III N2 status, a subgroup with poor historical 5 y survival (26%–36%; Goldstraw J Thorac Oncol 2016). Methods: Adults with resectable stg IIA–IIIB (N2; AJCC v8) NSCLC were randomized to neoadj NIVO 360 mg Q3W + chemo (4 cycles [cyc]) followed by adj NIVO 480 mg Q4W (13 cyc) or neoadj PBO Q3W + chemo (4 cyc) followed by adj PBO Q4W (13 cyc). Primary endpoint: EFS per BICR. Exploratory analysis: efficacy and safety in pts with BL clinical stg III N2 or non N2 disease (dz). Results: BL characteristics were generally similar between pts with stg III N2 (NIVO, 91; PBO, 90) and non N2 dz (55; 57), and between treatment (tx) arms, except a higher percent of pts with N2 dz had NSQ histology and ECOG PS 0 (both arms). Pts with N2 dz had improved EFS with NIVO vs PBO (HR 0.46; 1 y EFS 70% vs 45%) and higher pCR (22.0% vs 5.6%; median f/u 25.4 mo; Table). Pts with non N2 also had EFS benefit with NIVO vs PBO (HR 0.60; 1 y EFS 74% vs 62%) and higher pCR (25.5% vs 5.3%; Table). Surgical feasibility was similar between pts with N2 and non N2 dz and numerically higher with NIVO vs PBO. Of pts with N2 dz, 77% (NIVO) vs 73% (PBO) had definitive surgery (pneumonectomy 1% vs 14%; R0 resection 86% vs 86%); of pts with non N2 dz, 82% vs 79% had definitive surgery (pneumonectomy 13% vs 9%; R0 resection 84% vs 87%). Tumor downstaging postsurgery was seen in most pts with stg III dz and was deeper with NIVO vs PBO: 61% vs 50% (N2; 33% vs 14% to ypT0), 87% vs 76% (non N2; 27% vs 11% to ypT0). Of all pts with stg III dz, nodal downstaging postsurgery was 52% (NIVO) vs 45% (PBO); 46% vs 36% to ypN0. Grade 3–4 TRAEs occurred in 34% (NIVO) and 26% (PBO) of pts with N2; 29% and 21% of pts with non N2 dz. Conclusions: In this exploratory analysis, perioperative NIVO showed clinical benefit vs PBO in pts with stg III NSCLC, regardless of N2 status. Over half of pts with stg III dz had nodal downstaging with NIVO; majority downstaged to ypN0. This first comprehensive analysis by nodal status among pts with stg III dz from a global phase 3 study of perioperative immunotherapy further supports perioperative NIVO as a tx option for pts with resectable NSCLC. Clinical trial information: NCT04025879 . [Table: see text]

Background: In CheckMate 816, lower %RVT in primary tumor (PT) and lymph node (LN) after neoadjuvant (neoadj) NIVO + chemo correlated with improved EFS in patients (pts) with resectable NSCLC. To further evaluate %RVT as a surrogate for EFS, we report an exploratory analysis of efficacy with adjuvant (adj) NIVO after neoadj treatment (tx) by LN involvement, nodal (N) status, and %RVT in PT and LN in CheckMate 77T. Methods: Pts with resectable stage IIA-IIIB NSCLC were randomized to neoadj NIVO + chemo Q3W (up to 4 cycles [cyc]) followed by adj NIVO Q4W (up to 13 cyc) or neoadj placebo (PBO) + chemo Q3W (up to 4 cyc) followed by adj PBO Q4W (up to 13 cyc). Primary endpoint: EFS per BICR. This analysis, which included pts with pathologically evaluable samples who had definitive surgery and ≥ 1 adj tx dose, assessed EFS by LN involvement, N status, %RVT in PT and LN, and associations between %RVT and EFS per time-dependent ROC curve analysis. Results: BL characteristics were similar between tx arms (NIVO, 123; PBO, 134; median f/u, 33.3 mo). NIVO improved EFS v PBO regardless of LN involvement or N status (Table). A higher proportion of pts treated with NIVO had 0% RVT in PT and/or LN v PBO (52% v 20%). In pts with LN involvement, 2-y EFS rates with NIVO were higher in pts with 0% RVT in both PT and LN (90%) or 0% RVT in PT or LN (85%) v > 0% RVT in both PT and LN (76%). Area under the ROC curve for %RVT-PT in pts with PT-only disease was 0.83. 2-y EFS rates with NIVO were 94%, 77%, and 50% in pts with 0-5%, > 5-80%, and > 80% RVT-PT, respectively; similar results were seen in all pts with pathologically evaluable samples whether they received adj tx or not. Conclusions: In this exploratory analysis, NIVO improved EFS v PBO, particularly in pts with LN involvement and regardless of N status. %RVT also associated with EFS in a continuous manner, supporting %RVT as a surrogate for EFS and highlighting its prognostic value in pts who receive perioperative NIVO. Citation Format: Julie Stein Deutsch, Ashley Cimino-Mathews, Elizabeth Thompson, Edward Gabrielson, Peter Illei, Jaroslaw Jedrych, Ezra Baraban, Alex S. Baras, Mariano Provencio Pulla, Tina Cascone, Jonathan D. Spicer, Mark M. Awad, Fumihiro Tanaka, Jie He, Shun Lu, Cinthya Coronado Erdmann, Vipul Devas, Sumeena Bhatia, Janis M. Taube. Associations between percent residual viable tumor (%RVT) and efficacy with perioperative nivolumab (NIVO) for resectable NSCLC in CheckMate 77T [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr CT097.

658 Background: In the phase 3, randomized, double-blind CheckMate 274 trial, adjuvant NIVO demonstrated statistically significant and clinically meaningful disease-free survival (DFS) benefit vs PBO in pts with high-risk MIUC after radical surgery (RS) ± prior neoadjuvant cisplatin-based chemotherapy (NAC). With extended 3-y median follow-up, continued improvements in DFS were seen with NIVO vs PBO in the primary efficacy populations (intent-to-treat [ITT], tumor programmed death ligand 1 [PD-L1] expression ≥ 1%) and in pts with MIBC. Early trends in interim OS favored NIVO vs PBO in ITT and tumor PD-L1 ≥ 1% pts. Here we report additional efficacy outcomes for pts with MIBC. Methods: Pts were randomized 1:1 to NIVO 240 mg every 2 wk or PBO for ≤ 1 y of adjuvant treatment, stratified by tumor PD-L1 expression, nodal status, and prior NAC. Primary endpoints were DFS in ITT and tumor PD-L1 expression ≥ 1% pts. OS in ITT and PD-L1 ≥ 1% pts was a secondary endpoint. Analysis of MIBC pts was exploratory. MIBC OS data are from preplanned interim analyses of ITT and PD-L1 ≥ 1% pts. OS follow-up is ongoing as the prespecified statistical boundaries for significance in ITT and PD-L1 ≥ 1% pts were not crossed at the time of these analyses. Results: Of 709 randomized pts (ITT), 560 (79%) had MIBC (NIVO, n = 279; PBO, n = 281); 284 (51%) of MIBC pts had prior NAC. With median follow-up of 36.1 mo (ITT), DFS improvement with NIVO vs PBO was consistent between all pts with MIBC (hazard ratio [HR] 0.63) and those with (HR 0.58) and without prior NAC (HR 0.69; Table). For OS, HRs favored NIVO vs PBO in all pts with MIBC (HR 0.70) and the tumor PD-L1 ≥ 1% subgroup (HR 0.48), as well as in pts with MIBC with (HR 0.74) and without prior NAC (HR 0.67). Safety was consistent with previous data in ITT pts; no new safety signals were identified. Conclusions: With 3-y median follow-up, consistent benefit in DFS was observed with NIVO vs PBO in all MIBC pts and across prior NAC subgroups. The HR for OS favored NIVO in all MIBC pts, in those with PD-L1 ≥ 1%, and regardless of prior NAC status. These results continue to support adjuvant NIVO as a standard of care for high-risk MIUC and MIBC, potentially providing an opportunity for a curative outcome. Clinical trial information: NCT02632409 . NIVOn NIVOMedian(95% CI), mo PBOn PBOMedian(95% CI), mo HR (95% CI) DFS All MIBC 279 25.6 (19.2–41.8) 281 8.5 (7.3–13.7) 0.63 (0.51–0.78) With prior NAC 142 19.6 (15.6–48.2) 142 8.3 (5.6–11.2) 0.58 (0.43–0.79) No prior NAC 137 25.9 (19.2–51.5) 139 13.7 (7.8–22.1) 0.69 (0.50–0.94) OS All MIBC 279 NR (45.0–NE) 281 39.9 (29.8–52.1) 0.70 (0.55–0.90) PD-L1 ≥ 1% 113 NR (NE–NE) 117 37.6 (26.9–NE) 0.48 (0.29–0.77) With prior NAC 142 55.2 (41.8–NE) 142 40.2 (28.8–53.7) 0.74 (0.53–1.03) No prior NAC 137 NR (40.7–NE) 139 37.7 (28.7–65.2) 0.67 (0.47–0.95) NE, not estimable; NR, not reached.

491 Background: CheckMate 274 demonstrated a significant improvement in disease-free survival (DFS) with nivolumab (NIVO) versus placebo (PBO) both in the intent-to-treat population (hazard ratio [HR], 0.70; 98.22% confidence interval [CI], 0.55–0.90; P < 0.001) and in patients (pts) with tumor programmed death ligand 1 (PD-L1) expression ≥ 1% assessed by the tumor proportion score (TPS) (HR, 0.55; 98.72% CI, 0.35–0.85; P < 0.001). An exploratory subgroup analysis showed a trend toward a DFS benefit with NIVO in pts with TPS < 1% (0.82; 95% CI, 0.63–1.06). To further characterize the relationship between PD-L1 expression and NIVO efficacy, we report an analysis of DFS based on PD-L1 expression in both tumor and immune cells using the combined positive score (CPS). Methods: CheckMate 274 is a phase 3, randomized, double-blind, multicenter trial of NIVO versus PBO in pts with high-risk muscle-invasive urothelial carcinoma after radical surgery. Pts were randomized 1:1 to NIVO 240 mg or PBO every 2 weeks intravenously for 1 year of adjuvant treatment. The primary endpoints of the study are DFS in the intent-to-treat population and in pts with TPS ≥ 1%. The Dako PD-L1 IHC 28-8 pharmDx assay was used to evaluate TPS. CPS was determined retrospectively from previously stained immunohistochemistry slides using the CPS algorithm. CPS was calculated as the number of both PD-L1 positive tumor and immune cells divided by the number of viable tumor cells in the evaluable tumor area, multiplied by 100; TPS was similarly calculated with the number of PD-L1 positive tumor cells as the numerator. This analysis only included pts with both quantifiable CPS and TPS. Results: Of the 629 pts with quantifiable TPS and CPS, 249 (40%) had TPS ≥ 1% (NIVO, n = 124; PBO, n = 125), 380 (60%) had TPS < 1% (NIVO, n = 191; PBO, n = 189), 557 (89%) had CPS ≥ 1 (NIVO, n = 281; PBO, n = 276), and 72 (11%) had CPS < 1 (NIVO, n = 34; PBO, n = 38). Within TPS < 1% pts, 81% (n = 309) had CPS ≥ 1. The number of pts and the DFS outcomes in pts with TPS ≥ 1% and CPS ≥ 1 are shown in the Table. In pts with TPS < 1% who also had CPS ≥ 1, median DFS (95% CI) was 19.2 (15.6–33.4) months with NIVO versus 10.1 (8.2–19.4) months with PBO. The HR for NIVO versus PBO in these pts was 0.73 (95% CI, 0.54–0.99). Conclusions: This exploratory analysis of PD-L1 expression by CPS showed a higher proportion of pts with CPS ≥ 1 than TPS ≥ 1%, and that most pts with TPS < 1% had CPS ≥ 1. In the CPS ≥ 1 subgroup, median DFS with NIVO was more than double that with placebo. These results support the conclusion that pts with TPS < 1% also benefit from adjuvant NIVO. Clinical trial information: NCT02632409. [Table: see text]

391 Background: The standard of care (SOC) for patients (pts) with MIUC is radical surgery ± cisplatin-based neoadjuvant chemotherapy (chemo), but many pts are cisplatin-ineligible. There is no conclusive evidence supporting adjuvant chemo in pts who did not receive neoadjuvant chemo and in those with residual disease after neoadjuvant cisplatin. This phase 3 trial of adjuvant nivolumab (NIVO) vs placebo (PBO) in pts with MIUC after radical surgery ± neoadjuvant cisplatin (CheckMate 274) aims to address an unmet need in these pts. We report the initial results. Methods: This is a phase 3, randomized, double-blind, multicenter trial of NIVO vs PBO in pts with high-risk MIUC (bladder, ureter, or renal pelvis) after radical surgery. Pts were randomized 1:1 to NIVO 240 mg Q2W or PBO for ≤ 1 year of adjuvant treatment. Pts had radical surgery within 120 days ± neoadjuvant cisplatin or were ineligible/declined cisplatin-based chemo, evidence of UC at high risk of recurrence per pathologic staging, were disease-free by imaging, and ECOG PS ≤ 1. Primary endpoints: disease-free survival (DFS) in all randomized pts (ITT population) and in pts with tumor PD-L1 expression ≥ 1%. DFS was stratified by nodal status, prior neoadjuvant cisplatin, and PD-L1 status. Non–urothelial tract recurrence-free survival (NUTRFS) in ITT pts and in pts with PD-L ≥ 1% is a secondary endpoint. Safety is an exploratory endpoint. Results: In total, 353 pts were randomized to NIVO (PD-L1 ≥ 1%, n = 140) and 356 pts to PBO (PD-L1 ≥ 1%, n = 142). The primary endpoint of DFS was met in ITT pts (median follow-up, 20.9 mo for NIVO; 19.5 mo for PBO) and in pts with PD-L1 ≥ 1%. DFS and NUTRFS were improved with NIVO vs PBO in both populations (Table). DFS improvement with NIVO was generally consistent across subgroups. Grade 3–4 treatment-related adverse events (TRAEs) occurred in 17.9% and 7.2% of pts in the NIVO and PBO arms, respectively. Conclusions: NIVO demonstrated a statistically significant and clinically meaningful improvement in DFS vs PBO for MIUC after radical surgery, both in ITT pts and pts with PD-L1 ≥ 1%. AEs were manageable and consistent with previous reports. These results support adjuvant NIVO as a new SOC for pts with MIUC with high risk for recurrence despite neoadjuvant chemo or those ineligible for and/or declining cisplatin-based chemo. Clinical trial information: NCT02632409 . Research Sponsor: Bristol Myers Squibb[Table: see text]

4585 Background: In the CheckMate 274 trial, disease-free survival (DFS) was significantly improved with nivolumab (NIVO) vs placebo (PBO) both in intent-to-treat (ITT) patients (pts) (hazard ratio [HR], 0.70; 98.22% confidence interval [CI], 0.55–0.90; P < 0.001) and in pts with tumor programmed death ligand 1 (PD-L1) expression ≥ 1% (HR, 0.55; 98.72% CI, 0.35–0.85; P < 0.001). We report results for the subgroup of pts with bladder cancer, the most predominant type of urothelial carcinoma. Methods: CheckMate 274 is a phase 3, randomized, double-blind trial of adjuvant NIVO vs PBO in high-risk muscle-invasive urothelial carcinoma (bladder, ureter, renal pelvis) after radical resection. Pts were randomized 1:1 to NIVO 240 mg intravenously every 2 weeks or PBO for ≤ 1 year of adjuvant treatment and stratified by nodal status, prior neoadjuvant cisplatin, and tumor PD-L1 expression. Pts had radical resection ± neoadjuvant chemotherapy and were at high risk of recurrence on final pathologic staging. Primary endpoints were DFS in ITT pts and in pts with PD-L1 ≥ 1%. Non–urothelial tract recurrence-free survival (NUTRFS) was a secondary endpoint, and distant metastasis-free survival (DMFS) was an exploratory endpoint. This exploratory analysis focused on the subgroup of pts with muscle-invasive bladder cancer (MIBC) after radical resection. Results: Of 709 randomized pts in the trial, 560 had MIBC (NIVO, n = 279; PBO, n = 281). With a minimum follow-up of 11.0 months, a DFS benefit was observed with NIVO vs PBO in these pts, regardless of tumor PD-L1 expression (Table). DFS probability at 12 months in all MIBC pts was 66% with NIVO and 45% with PBO. DFS was improved with NIVO vs PBO across subgroups according to age, sex, ECOG performance status, nodal status, and PD-L1 expression status. Improvement in NUTRFS and DMFS with NIVO vs PBO was also observed (Table). Grade 3–4 treatment-related adverse events occurred in 17% and 6% of pts in the NIVO and PBO arms, respectively. Conclusions: Improvement in DFS was observed with NIVO over PBO in pts with MIBC after radical resection regardless of tumor PD-L1 expression. The DFS benefit was observed in all prespecified subgroups. These results further support adjuvant NIVO as a standard-of-care treatment for pts with high-risk MIBC after radical resection ± neoadjuvant cisplatin-based chemotherapy. Clinical trial information: NCT02632409. [Table: see text]

LBA8000 Background: NIVO + chemo is an established standard of care neoadjuvant treatment (tx) for eligible patients (pts) with resectable NSCLC and has shown statistically significant and clinically meaningful improvements in EFS and pCR in the phase 3 CheckMate 816 study. Here, we report the planned final analysis of OS from CheckMate 816 at 5-y follow-up (f/u). Methods: Adults with stage IB (≥ 4 cm)–IIIA (per AJCC v7) resectable NSCLC, ECOG PS ≤ 1, and no known EGFR / ALK alterations were randomized 1:1 to receive neoadjuvant NIVO + chemo Q3W or chemo alone Q3W for 3 cycles, followed by surgery. Primary endpoints were EFS and pCR (both by blinded independent review). OS was a key prespecified, statistically powered secondary endpoint that was tested hierarchically. Exploratory analyses included OS by ctDNA clearance and pCR status. Results: At a median f/u of 68 mo (range, 60–85; database lock, 23 Jan 2025), neoadjuvant NIVO + chemo demonstrated a statistically significant OS benefit vs chemo alone (median [95% CI], not reached [NR] vs 73.7 mo [47.3–NR]; HR [95% CI], 0.72 [0.523–0.998]; P = 0.0479); 5-y OS rates were 65% vs 55%. OS favored NIVO + chemo in the subgroups defined by tumor PD-L1 expression, baseline disease stage, and histology (Table). In an exploratory analysis in pts with ctDNA+ at baseline (NIVO + chemo, n = 43; chemo, n = 43), pts with presurgical ctDNA clearance (56% vs 35%) had continued OS improvement vs those without across both tx arms (HR [95% CI]: NIVO + chemo, 0.38 [0.15–1.00]; chemo, 0.39 [0.14–1.11]). Furthermore, pts who had pCR with NIVO + chemo had sustained OS improvement vs those without (HR [95% CI], 0.11 [0.04–0.36]; 5-y OS rates, 95% vs 56%). Neoadjuvant NIVO + chemo continued to improve EFS vs chemo (median [95% CI], 59.6 [31.6–NR] vs 21.1 mo [16.5–36.8]; HR [95% CI], 0.68 [0.51–0.91]); 5-y EFS rates were 49% vs 34%. No new safety signals were observed at this long-term f/u. Conclusions: CheckMate 816 is the only neoadjuvant-only immunotherapy phase 3 trial to demonstrate a statistically and clinically significant OS benefit at 5 y for a resectable solid tumor. Pts with pCR with neoadjuvant NIVO + chemo had a ~90% reduction in their risk of death by 5 y compared with those without pCR. The findings show long-term survival benefit from a short course of neoadjuvant NIVO + chemo and affirm a paradigm shift in the tx of resectable NSCLC without actionable genomic alterations. Clinical trial information: NCT02998528 . All pts PD-L1 < 1% PD-L1 ≥ 1% Stage IB/II Stage IIIA Squamous Non-squamous NIVO + chemo (N = 179) vs chemo (N = 179) NIVO + chemo (n = 78) vs chemo (n = 77) NIVO + chemo (n = 89) vs chemo (n = 89) NIVO + chemo (n = 65) vs chemo (n = 61) NIVO + chemo (n = 113) vs chemo (n = 116) NIVO + chemo (n = 87) vs chemo (n = 95) NIVO + chemo (n = 92) vs chemo (n = 84) Median OS, mo NR vs 73.7 NR vs 61.8 NR vs 73.7 NR vs 76.8 NR vs 73.7 NR vs 73.7 NR vs NR HR (95% CI) 0.72 (0.523–0.998) 0.89 (0.57–1.41) 0.51 (0.31–0.84) 0.77 (0.44–1.35) 0.70 (0.47–1.05) 0.71 (0.46–1.11) 0.72 (0.45–1.16)

LBA02-08 RESULTS FROM THE EXTENDED FOLLOW-UP IN PATIENTS WITH MUSCLE-INVASIVE BLADDER CANCER IN THE CHeckMATE 274 TRIAL

Clonal Dynamics of Gene Mutations during Oral Azacitidine Maintenance Therapy in Patients with Acute Myeloid Leukemia (AML): Outcomes from the QUAZAR AML-001 Trial

Background: In AEGEAN, perioperative durvalumab (D) + neoadjuvant (neoadj) chemotherapy (CT) significantly improved pathological complete response (pCR) and event-free survival (primary endpoints), and major pathological response (MPR; key secondary endpoint), with manageable safety vs neoadj CT alone in patients with resectable NSCLC. We report exploratory ctDNA analyses during neoadj treatment (Tx) and associations of ctDNA dynamics and clearance with pathological response, including pCR, MPR and percentage residual viable tumor (%RVT). Methods: AEGEAN is a double-blind placebo (PBO)-controlled study (NCT03800134). Adults with Tx-naïve resectable NSCLC (stage II-IIIB[N2]; AJCC 8th ed) were randomized (1:1) to receive neoadj CT + D or PBO IV (Q3W, 4 cycles) prior to surgery (Sx), followed by D or PBO IV (Q4W, 12 cycles), respectively, after Sx. Evaluable resected samples from patients in the modified intent-to-treat (mITT) population (patients without known EGFR/ALK aberrations) were assessed centrally for %RVT and determination of pCR (absence of any RVT in resection specimen, including primary tumor and all sampled lymph nodes) and MPR (≤10% RVT in primary tumor) per IASLC recommendations. Plasma samples were collected prior to each neoadj Tx cycle (at baseline [BL], C2D1, C3D1, and C4D1) and before Sx. ctDNA analysis was performed using patient-specific, tumor-informed assays, following identification of mutations in Tx-naïve, diagnostic biopsies by whole exome sequencing. ctDNA variant allele fractions (VAFs; mutant sequences as a % of total sequence reads at ctDNA panel sites) and dynamics, including ctDNA clearance, were assessed during neoadj Tx, and their potential associations with pCR, MPR, or %RVT were evaluated. Results: ctDNA was evaluated in 831 samples from 186 patients (D arm, n=90; PBO arm, n=96) in the mITT population from the interim pCR analysis cohort (n=402). ctDNA dynamics were assessed during neoadj Tx in relation to whether patients had a pathological response at surgery; patients without surgery were designated as non-responders. BL VAF levels were not significantly different between patients who had tumors with vs without pCR (D arm, P=0.09; PBO arm, P=0.7) or MPR (D arm, P=0.4; PBO arm, P=0.8); however, on-Tx VAF levels were significantly lower in the D arm from C2D1 onwards in patients with vs without pCR (P≤0.001) or MPR (P≤0.01) and in the PBO arm from C3D1 for pCR (P≤0.003) or C2D1 for MPR (P≤0.002). %RVT was significantly lower in patients with vs without ctDNA clearance from C2D1 onwards in the D arm (median, <5% vs ≥30%, P≤0.01) and from C3D1 onwards in the PBO arm (median, 10% vs ≥50%, P≤0.0004). Conclusions: In AEGEAN, reduced VAF levels during neoadj Tx appeared associated with pCR or MPR. Patients in whom ctDNA clearance was observed tended to have a lower %RVT, from C2D1 in the D arm and from C3D1 in the PBO arm. Citation Format: Davina Gale, Zhou Zhu, Zhongwu Lai, Martin Reck, David Harpole, Janis M. Taube, Tetsuya Mitsudomi, Maximilian Hochmair, Thomas Winder, László Urbán, Jeronimo Rodriguez-Cid, Quincy Chu, Jamie Chaft, Ross Stewart, Darren Hodgson, Gary J. Doherty, John V. Heymach. Associations of ctDNA levels during neoadjuvant treatment with pathological response in patients with resectable NSCLC from the phase 3 AEGEAN trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT238.

Prognostic Impact of NPM1 and FLT3 Mutations at Diagnosis and Presence of Measurable Residual Disease (MRD) after Intensive Chemotherapy (IC) for Patients with Acute Myeloid Leukemia (AML) in Remission: Outcomes from the QUAZAR AML-001 Trial of Oral Azacitidine (Oral-AZA) Maintenance

LBA9026 Background: In CheckMate 9LA (NCT03215706), 1L NIVO + IPI combined with 2 cycles of chemo was shown to provide survival benefit vs chemo alone in pts with metastatic NSCLC. Here, we report updated efficacy and safety with a 3-year minimum follow-up, as well as exploratory biomarker analyses from this study. Methods: Adults with stage IV or recurrent NSCLC, no known sensitizing EGFR/ ALK alterations, and ECOG performance status ≤ 1 were randomized 1:1 to NIVO 360 mg Q3W + IPI 1 mg/kg Q6W + 2 cycles of chemo (n = 361) or 4 cycles of chemo alone (n = 358). Pts were stratified by tumor PD-L1 expression, sex, and histology. Pts with non-squamous (NSQ) NSCLC in the chemo-alone arm could receive pemetrexed maintenance. Assessments included overall survival (OS), progression-free survival (PFS), and objective response rate (ORR). For all pts with NSQ NSCLC and with tissue evaluable for mutational analysis (n = 313), the FoundationOne CDxTM assay was used to identify mutant (mut) or wild type (wt) KRAS and STK11 genes. Exploratory assessments included evaluation of OS and PFS with NIVO + IPI + chemo vs chemo by mutation status and safety. Results: At a minimum follow-up of 36.1 mo (database lock: Feb 15, 2022), pts continued to derive long-term, durable OS benefit with NIVO + IPI + chemo vs chemo (HR, 0.74 [95% CI, 0.62–0.87]); 3-y OS rates were 27% vs 19%. Clinical benefit with NIVO + IPI + chemo vs chemo was observed in all randomized pts and across most subgroups, including by PD-L1 expression level (Table) or histology. In an exploratory analysis in pts evaluable for mutations including KRAS and STK11, OS appeared to be improved with NIVO + IPI + chemo vs chemo (median OS, 16.3 vs 13.1 mo). Similar trends of prolonged OS with NIVO + IPI + chemo vs chemo were also seen in pts with or without KRAS mutation (median OS, mut: 19.2 vs 13.5 mo; wt: 15.6 vs 12.7 mo) or STK11 mutation (mut: 13.8 vs 10.7 mo; wt: 17.8 vs 13.9 mo), respectively. Additional efficacy outcomes will be presented. No new safety signals were identified with extended follow-up. Conclusions: With a 3-year minimum follow-up, 1L NIVO + IPI + chemo demonstrated long-term, durable efficacy benefit vs chemo in pts with metastatic NSCLC. Survival benefit of NIVO + IPI + chemo vs chemo was observed regardless of KRAS and STK11 mutation status. Clinical trial information: NCT03215706. [Table: see text]

4O Nivolumab (NIVO) + ipilimumab (IPI) versus chemotherapy (chemo) as first-line (1L) treatment for advanced NSCLC (aNSCLC) in CheckMate 227 part 1: Efficacy by KRAS, STK11, and KEAP1 mutation status

Outcome of Patients with Complex Karyotype in a Phase 3 Randomized Study of Idelalisib Plus Rituximab for Relapsed Chronic Lymphocytic Leukemia

Background: CheckMate 816 (NCT02998528), a randomized phase 3 study of neoadjuvant NIVO + chemo vs chemo for resectable NSCLC, met its first primary endpoint with a statistically significant improvement in pathological complete response (pCR) rate (24% vs 2%; odds ratio 13.94 [99% CI, 3.49-55.75; P < 0.0001]). pCR benefit was consistent across key subgroups, including disease stages, histologies, and PD-L1 expression levels. Notably, neoadjuvant NIVO + chemo did not impede feasibility of surgery nor increase incidence of surgical complications or adverse events (AEs) vs chemo alone. We report results from the first prespecified interim analysis of EFS, the other primary endpoint. Methods: Adults with stage IB (≥ 4 cm)-IIIA (per AJCC 7th ed) resectable NSCLC, ECOG PS ≤ 1, and no known EGFR/ALK alterations were randomized to NIVO 360 mg + chemo Q3W or chemo Q3W for 3 cycles (n = 179 each). Primary endpoints were EFS and pCR (both assessed by blinded independent review) in the randomized population. EFS was defined as the length of time from randomization to any disease progression precluding surgery, disease progression or recurrence after surgery, or death due to any cause. An exploratory analysis of EFS by pCR status was conducted. Results: At a median follow-up of 29.5 mo (database lock, October 20, 2021), neoadjuvant NIVO + chemo significantly improved EFS vs chemo in the randomized population (median [95% CI], 31.6 mo [30.2-not reached (NR)] vs 20.8 mo [14.0-26.7]; HR [97.38% CI], 0.63 [0.43-0.91]; P = 0.0052; 2-year EFS rates, 64% vs 45%). EFS results in the subgroups by disease stages, histologies, and PD-L1 expression levels are shown in the Table: In the pooled patient population (NIVO + chemo and chemo arms combined), EFS was improved in patients with pCR compared with those without (median, NR vs 21.1 mo; HR [95% CI], 0.11 [0.04-0.29]). Incidence of grade 3-4 treatment-related (33.5% vs 36.9%) and surgery-related AEs (11.4% vs 14.8%) was similar between the NIVO + chemo and chemo arms, as reported previously. Conclusions: In CheckMate 816, neoadjuvant NIVO + chemo showed a statistically significant and clinically meaningful improvement in EFS vs chemo alone. These results, along with the significant improvement in pCR, support NIVO + chemo as a potential new treatment option for patients with stage IB-IIIA resectable NSCLC. Subgroups Median EFS, mo (95% CI) HR (95% CI) NIVO + chemo Chemo Overall (n = 358) 31.6 (30.2-NR) 20.8 (14.0-26.7) 0.63 (0.43-0.91)a Baseline disease stage IB-II (n = 127) NR (27.8-NR) NR (16.8-NR) 0.87 (0.48-1.56) IIIA (n = 228) 31.6 (26.6-NR) 15.7 (10.8-22.7) 0.54 (0.37-0.80) Tumor histology Squamous (n = 182) 30.6 (20.0-NR) 22.7 (11.5-NR) 0.77 (0.49-1.22) Non-squamous (n = 176) NR (27.8-NR) 19.6 (13.8-26.2) 0.50 (0.32-0.79) PD-L1 expression level < 1% (n = 155) 25.1 (14.6-NR) 18.4 (13.9-26.2) 0.85 (0.54-1.32) ≥ 1% (n = 178) NR (NR-NR) 21.1 (11.5-NR) 0.41 (0.24-0.70) 1-49% (n = 98) NR (27.8-NR) 26.7 (11.5-NR) 0.58 (0.30-1.12) ≥ 50% (n = 80) NR (NR-NR) 19.6 (8.2-NR) 0.24 (0.10-0.61) a97.38% CI reported. Chemo, chemotherapy; CI, confidence interval; EFS, event-free survival; HR, hazard ratio; mo, months; NIVO, nivolumab; NR, not reached; PD-L1, programmed death ligand 1. Citation Format: Nicolas Girard, Jonathan Spicer, Mariano Provencio, Shun Lu, Stephen Broderick, Mark M. Awad, Tetsuya Mitsudomi, Keith Kerr, Julie Brahmer, Scott J. Swanson, Enriqueta Felip, Changli Wang, Gene B. Saylors, Ke-Neng Chen, Fumihiro Tanaka, Moishe Liberman, Cecile Dorange, Javed Mahmood, Junliang Cai, Patrick M. Forde. Nivolumab (NIVO) + platinum-doublet chemotherapy (chemo) vs chemo as neoadjuvant treatment for resectable (IB-IIIA) non-small cell lung cancer (NSCLC): Event-free survival (EFS) results from the phase 3 CheckMate 816 trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr CT012.