KEYNOTE-671 Trial

[Slide 1] Node-Negative (cN0) Node-Positive (cN1/cN2) Pembrolizumab Placebo Pembrolizumab Placebo n = 148 n = 142 n = 248 n = 258 EFS, median (95% CI), mo 69.1 (37.5-NR) 19.6 (14.3-25.8) 47.6 (27.7-68.9) 17.9 (14.0-22.2) HR (95% CI) 0.56 (0.40-0.77) 0.57 (0.45-0.72) OS, median (95% CI), mo NR (NR-NR) NR (47.8-NR) NR (63.7-NR) NR (45.7-NR) HR (95% CI) 0.70 (0.47-1.04) 0.77 (0.58-1.01) MPR (95% CI), % 33.1 (25.6-41.3) 10.6 (6.0-16.8) 28.2 (22.7-34.3) 11.2 (7.7-15.7) Difference (95% CI) 22.5 (13.3-13.7) 17.0 (10.2-23.9) pCR (95% CI), % 20.3 (14.1-27.7) 4.9 (2.0-9.9) 16.5 (12.1-21.8) 3.5 (1.6-6.5) Difference (95% CI) 15.3 (8.1-23.1) 13.0 (8.1-18.5) NR, not reached

[Slide 1] Should we stratify by pCR and MRD? AEGEAN: Perioperative Durvalumab MRD+ Are we sure that ADJ IO will 100 Poorest 10.1% (n=17) overcome this bad prognosis? prognosis treatment now or at 80 Disease radiological PD No pCR & MRD- 40 Proportion of patients (%) 60 May be the optimal 81.5% 89,9% ? Population to be treated (n=151) (n=123) With ADJ treatment, but IO? Are we sure that pCR & MRD- 20 we need to "overtreat" 18.5% Best (n=28) prognosis this population 0 with ADJ IO? MRD-evaluable at the MRD- (n=151) Post-surgical landmark (n=168) Hwr, risk of false negative MRD+ MRD- No pCR pCR 81.5% of patients with MRD- do not reach pCR, how to treat this intermediate prognosis? Reck - ESMO 2024 * Reck - ASCO 2025 (Slide courtesy of Prof Peters, modified)

[Slide 1] Background In the phase 3 KEYNOTE-671 study of early-stage NSCLC, perioperative pembro plus neoadjuvant chemotherapy (chemo) significantly improved event-free survival (EFS), overall survival (OS), major pathological response, and pCR VS neoadjuvant chemo. EFS was prolonged in exploratory analyses of participants (pts) who achieved pCR (HR, 0.33; 95% CI, 0.09-1.22). We report efficacy results in pts with pCR from KEYNOTE-671 after 5 years of follow-up. Methods Eligible pts aged ≥18 y with previously untreated, resectable stage II, IIIA, or IIIB (N2) NSCLC per AJCC v8 were randomized 1:1 to pembro 200 mg or placebo Q3W plus chemo for 4 cycles, followed by surgery then adjuvant pembro 200 mg or placebo Q3W for up to 13 cycles (~9 mo). Primary endpoints included EFS per RECIST v1.1 by investigator assessment; secondary endpoints included pCR by blinded central laboratory pathologist. Results Of 397 pts randomized to pembro and 400 to placebo, 72 (18.1%) and 16 (4.0%) achieved pCR, respectively, of whom 67 pts (93.1%) in the pembro arm and 15 pts (93.8%) in the placebo arm received ≥1 adjuvant dose, and 47 (65.3%) and 12 (75.0%), respectively, completed adjuvant therapy. Median time from randomization to data cutoff (July 3, 2025) for pts with pCR was 62.3 (range, 43.3-84.7) mo. More pts achieved pCR in the pembro VS placebo arm across baseline disease characteristic subgroups (Table). Among pts with pCR, 5-year EFS rates were 80.8% (95% CI, 68.3%-88.8%) and 55.7% (95% CI, 26.0%-77.6%), respectively; the EFS HR was 0.37 (95% CI, 0.14-1.00). Table: 223MO Pembro arm, % (95% CI)Placebo arm, % (95% CI)Difference, % (95% CI) Overall (n = 797) 18.1 (14.5-22.3) 4.0 (2.3-6.4) 14.2 (10.1-18.7) Disease stage II (n = 239) 24.6 (17.1-33.4) 3.3 (0.9-8.2) 21.3 (13.2-30.2) III (n = 558) 15.4 (11.4-20.2) 4.3 (2.2-7.4) 11.1 (6.4-16.2) Nodal stage NO (n = 290) 20.3 (14.1-27.7) 4.9 (2.0-9.9) 15.3 (8.1-23.1) N1 (n = 155) 18.3 (10.6-28.4) 4.1 (0.9-11.5) 14.2 (4.5-24.6) N2 (n = 351) 15.7 (10.5-22.1) 3.2 (1.2-6.9) 12.4 (6.6-19.1) PD-L1 TPS >50% (n = 266) 27.3 (19.9-35.7) 6.0 (2.6-11.4) 21.3 (12.8-30.2) 1%-49% (n = 242) 13.4 (8.0-20.6) 1.7 (0.2-6.1) 11.6 (5.5-18.9) <1% (n = 289) 13.8 (8.5-20.7) 4.0 (1.5-8.4) 9.8 (3.5-17.0) TPS, tumor proportion score. "Excludes 1 pt with NX stage. Conclusions Perioperative pembro plus neoadjuvant chemo improved pCR across subgroups of baseline disease characteristics and continued to prolong EFS VS neoadjuvant chemo after 5 years of follow-up in pts who achieved pCR. These data continue to support the use of perioperative pembro plus neoadjuvant chemo for resectable early-stage NSCLC, including in pts with pCR.

[Slide 1] Background In the phase 3 KEYNOTE-671 study of early-stage NSCLC, perioperative pembro plus neoadjuvant chemotherapy (chemo) significantly improved event-free survival (EFS), OS, major pathological response, and pCR VS neoadjuvant chemo. EFS was prolonged in exploratory analyses of participants (pts) who did not achieve pCR (HR, 0.69; 95% CI, 0.55-0.85). We report results in pts without pCR from KEYNOTE-671 after 5 years of follow-up. Methods Eligible pts aged >18 y with previously untreated, resectable stage II-IIIB (N2) NSCLC per AJCC v8 were randomized 1:1 to pembro 200 mg or placebo Q3W plus chemo for 4 cycles, then surgery and adjuvant pembro or placebo Q3W for up to 13 cycles (~9 mo). Primary endpoints included EFS per RECIST v1.1 by investigator and OS; secondary endpoints included pCR by blinded central laboratory pathologist. Results Of 397 pts randomized to pembro and 400 to placebo, 325 (81.9%) and 384 (96.0%), respectively, did not achieve pCR, of whom 223 pts (68.6%) in the pembro arm and 252 pts (65.6%) in the placebo arm received ≥1 adjuvant dose, and 144 (44.3%) and 162 (42.2%), respectively, completed adjuvant therapy. Median time from randomization to data cutoff (July 3, 2025) for pts without pCR was 60.2 (range, 42.6-85.8) mo. The HR for EFS was 0.69 (95% CI, 0.57-0.83), favoring the pembro VS placebo arm (Table). OS data for this subgroup are not yet mature. Grade >3 treatment-related AEs occurred in 143 of 324 pts (44.1%) treated with pembro and 146 of 383 (38.1%) treated with placebo. Grade >3 immune-mediated AEs and infusion reactions occurred in 21 (6.5%) and 7 pts (1.8%), respectively. Table: 222MO EFS Pembro arm Placebo arm Pts without pCR n = 325 n = 384 Median (95% CI), mo31.9 (22.2-50.3)18.1 (14.5-21.7) 5-y rate (95% CI), % 42.9 (37.2-48.5)25.2 (20.4-30.3) HR (95% CI) 0.69 (0.57-0.83) Clinical stage II n 89 n 117 HR (95% CI) 0.68 (0.46-1.00) III n = 236 n 267 HR (95% CI) 0.67 (0.53-0.83) Clinical nodal status cN0 n 118 n 135 HR (95% CI) 0.66 (0.47-0.92) cN1 n = 67 n = 70 HR (95% CI) 0.60 (0.38-0.95) cN2 n = 140 n = 179 HR (95% CI) 0.75 (0.57-0.98) Histology Nonsquamous n 174 n = 219 HR (95% CI) 0.84 (0.65-1.08) Squamous n = 151 n = 165 HR (95% CI) 0.55 (0.41-0.74) PD-L1 TPS >50% n 96 n 126 HR (95% CI) 0.58 (0.40-0.84) 1%-49% n = 110 n 113 HR (95% CI) 0.63 (0.45-0.88) <1% n = 119 n = 145 HR (95% CI) 0.83 (0.62-1.11) Conclusions Among pts without pCR in KEYNOTE-671, perioperative pembro plus neoadjuvant chemo continued to prolong EFS after 5 years of follow-up, regardless of baseline clinical characteristics. These data support the use of perioperative pembro plus neoadjuvant chemo for resectable early-stage NSCLC.

[Slide 1] Does pCR = Cure in early NSCLC? KEYNOTE-671 5-year update (#ELCC26) @DrRishabhOnco pCR achieved: Resectable stage pCR associated II-IIIB (N2) NSCLC 18.1% vs 4.0% with durable benefit n=72 vs 16 Pembrolizumab + Chemo Not just response Surgery translates into Adjuvant Pembrolizumab long-term outcomes Chemo alone Small subgroup Surgery CI wide Placebo If pCR achieved outcomes diverge significantly 5-year EFS (pCR patients): 55-year EFS 80.8% 55.7% HR 0.37 (95% CI 0.14-1.00) Perioperative pembrolizumab improves depth + durability