CheckMate-77T Trial

[Slide 1] FDA Q Search III Menu IN THIS SECTION Resources for Information I Approved Drugs FDA approves neoadjuvant/adjuvant nivolumab for resectable non-small cell lung cancer f Share X Post Email

[Slide 2] CM 77T (perioperative NIVO): outcomes by neoadjuvant cycles pCR by number of completed neoadjuvant treatment cycles 4 cycles < 4 cycles All patients Patients with resection All patients Patients with resection Difference Difference Difference Difference 21.3%ᵃ 25.7%d 18.4%g 35.0% 50 50 40 40 35.0%k 32.3%e pCR rate (%) 30 26.7%b 20 pCR rate (%) 30 20 18.4%h 10 5.4%c 6.5%f 10 0% 0%¹ 0 0 NIVO PBO NIVO PBO NIVO PBO NIVO PBO n/N 51/191 11/205 51/158 11/168 n/N 7/38 0/27 7/20 0/10 Of 7 patients who had a pCR in the NIVO arm, 3 received 3 neoadjuvant cycles, and 4 received 2 neoadjuvant cycles Follow-up, median (range): 25.4 (15.7-44.2) months. *195% Cl: *14.3-28.4, 6-33.6, 2.7-9.4, "17.4-33.9, *25.1-40.2, 3.3-11.4, #2.9-33.4, 17.7-34.3, 0-12.8, 2.5-56.7, 15.4-59.2, 0-30.8. --- [Slide 3] CM 77T (perioperative NIVO): outcomes by neoadjuvant cycles EFS by number of completed neoadjuvant treatment cycles 4 cycles < 4 cycles NIVO PBO NIVO PBO (n = 191) (n = 205) (n = 38) (n = 27) 100 Median EFS, mo NR 19.8 100 Median EFS, mo NR 7.8 HR (95% CI) 0.57 (0.42-0.79) HR (95% CI) 0.51 (0.23-1.11) 80 76%a 80 62%c EFS (%) 60 NIVO EFS (%) 60 61%ᵇ NIVO 40 40 PBO 36%d PBO 20 20 0 0 0 6 12 18 24 30 36 42 0 6 12 18 24 30 36 42 Months from randomization Months from randomization No. at risk NIVO 191 152 123 101 63 18 4 0 38 21 18 14 6 2 0 0 PBO 205 155 112 75 41 19 6 0 27 10 6 3 3 0 0 0 Follow-up, median (range): 25.4 (15.7-44.2) months. ***95% Cl: "68-81; 541m 42-76; 15-57. --- [Slide 4] CM 77T (perioperative NIVO): outcomes by neoadjuvant cycles Summary In these exploratory analyses from CheckMate 77T, patients with resectable NSCLC had improved efficacy with perioperative NIVO vs placebo whether they completed 4 or < 4 neoadjuvant cycles - -pCR or MPR rates were similar among patients who underwent definitive surgery regardless of the number of neoadjuvant NIVO + chemo cycles Most patients who could receive adjuvant NIVO after neoadjuvant NIVO + chemo received the full 13 adjuvant cycles and had a manageable safety profile These results further support perioperative NIVO as a potential new treatment option, that builds on the standard of care neoadjuvant NIVO + chemo, for patients with resectable NSCLC

[Slide 1] CheckMate 77T: clinical outcomes with perioperative NIVO by nodal status CheckMate 77T study design Key eligibility criteria NIVO 360 mg Q3W Radiologic Resectable, stage IIA (> 4 cm)-IIIB restaging (N2) NSCLC (per AJCC 8th edition) + NIVO 480 mg Q4W Surgery No prior systemic anti-cancer chemob Q3W (13 cycles) treatment N = 461 (4 cycles) ECOG PS 0-1 R Within 6 weeks Follow-up No EGFR mutations/known ALK 1:1 post-neoadjuvant alterations treatment PBO Q3W Radiologic restaging Stratified by + PBO Q4W histology (NSQ vs SQ), Surgery disease stage (II vs III), chemob Q3W (13 cycles) and tumor PD-L1 ( 1% vs < 1% vs (4 cycles) not evaluable/indeterminate) Primary endpoint Secondary endpoints Exploratory analyses EFS by BICR pCR by BIPR os Clinical outcomes by MPR by BIPR Safety clinical stage III N2 or non-N2 status Database lock date: September 6, 2023; median follow-up (range): 25.4 months (15.7-44.2). NCT04025879 NSQ: cisplatin pemetrexed, carboplatin + pemetrexed, or carboplatin + paclitaxel; SQ: cisplatin + docetaxel or carboplatin + paclitaxel.

[Slide 1] The NEW ENGLAND JOURNAL of MEDICINE Perioperative Nivolumab in Resectable Lung Cancer A PLAIN LANGUAGE SUMMARY Based on the NEJM publication: Perioperative Nivolumab in Resectable Lung Cancer by T. Cascone et al. (published May 16, 2024) In this trial, researchers assessed whether adding Nivolumab, a fully human anti-programmed death 1 adjuvant nivolumab to neoadjuvant nivolumab plus (PD-1) antibody, plus platinum-doublet chemothera- chemotherapy would improve outcomes in patients py, is now standard neoadjuvant therapy for eligible with resectable non-small-cell lung cancer (NSCLC). patients with NSCLC. WHY WAS THE TRIAL DONE? PATIENTS An estimated 30% to 55% of patients with resectable NSCLC have disease relapse after surgery with curative intent. A perioperative approach 111111 including immunotherapy with nivolumab might reduce risk. Resectable Non-Small-Cell WHO 461 adults Lung Cancer (NSCLC) Median age, 66 years (range, 35-86 years) HOW WAS THE TRIAL CONDUCTED? Men: 71%; Women: 29% 461 patients were assigned to receive either neoadjuvant nivolumab plus CLINICAL Resectable tumor platinum-doublet chemotherapy or neoadjuvant placebo plus platinum-doublet STATUS chemotherapy every 3 weeks for 4 cycles, followed by surgery and adjuvant Stage IIA (>4 cm) to IIIB nivolumab or placebo every 4 weeks for 1 year. The primary outcome was (N2 node stage) NSCLC event-free survival, with events defined as disease progression or recurrence, surgical difficulty, or death. 229 Patients Neoadjuvant Period 232 Patients Before surgery TRIAL DESIGN RANDOMIZED PLACEBO-CONTROLLED DOUBLE-BLIND 360 mg Platinum-doublet Placebo Platinum-doublet Nivolumab Chemotherapy Placebo Chemotherapy MULTINATIONAL, INCLUDING COUNTRIES IN NORTH AMERICA, Adjuvant Period SOUTH AMERICA, EUROPE, ASIA, AND AUSTRALIA Within 90 days after surgery Nivolumab Placebo 480 mg 1 Copyright © 2024 Massachusetts Medical Society. --- [Slide 2] the NEW ENGLAND JOURNAL of MEDICINE RESULTS EVENT-FREE SURVIVAL in this prespecified interim analysis, the percentage of patients with event-free survival at 18 months was significantly higher in the nivolumab group than in the chemotherapy group. Patients in the nivolumab group were Percentage of Patients with Event free Servival Harand - for disease progression - and 058 (si, - a 542-031) Process 42% less likely 70.2% 50.0% Name to have disease progression or recurrence, surgery abandon- Chemotherapy ment due to unresectability, or death than those in the chemotherapy group. 0 1 . 1 # Months ADVERSE EVENTS Pathological complete response and major pathological response (secondary outcomes) also favored nivolumab over chemotherapy Nivolumab Major Pathological Response Pathological Complete Response 32.5% Difference FINCE 158-30-6 Difference as no. --- ONLY - 4.01 - --- - - M PINO Chemotherapy 25.2% Grade ) or 4 treatment-related 35.4% adverse events occurred more often 25.3% in the nivolumab group than in the 12.1% 4.7% chemotherapy group | No new safety signals were reported Nivolumab Chematherapy Nature Changement with nivolumab. LIMITATIONS AND REMAINING QUESTIONS CONCLUSIONS Black patients were underrepresented in the trial population. in adults with resectable stage IIA to HB Long-term survival benefit of perioperative nivols- NSCLC, perioperative nivolumab significantly mab will be ascertained as the trial data mature. improved event-free survival at is months as compared with chemotherapy. LINES: FULL ARTICLE I NEJM QUICK TAKE EDITORIAL FURTHER INFORMATION Total registration: ClinicalTrials.gov number, NCT04025879 Funding Bristol Myers Squibb Full citation: Cascone 1, Awad MM, Spicer 3D, at at Perisperative nivolumab - resectable lung cancer N Engl) Med 2024,190,1756-69. DOI: 0.1056/NEjMoa2311926 For personal use only. Any commercial rease at NIJM Group content requires permission. Copyright c 2024 Massachusetts Medical Society All rights reserved. 2

[Slide 1] MADRID 2023 ESMO congress CheckMate 77T: Phase 3 study comparing neoadjuvant nivolumab plus chemotherapy with neoadjuvant placebo plus chemotherapy followed by surgery and adjuvant nivolumab or placebo for previously untreated, resectable stage II-IIIB NSCLC Tina Cascone, Mark M. Awad,2 Jonathan Spicer,³ Jie He,4 Shun Lu,⁵ Boris Sepesi, Fumihiro Tanaka,¹ Janis M. Taube,⁷ Robin Cornelissen,⁸ Libor Havel,9 Jaroslaw Kuzdzal, 10 Lubos 8. Petruzelka, Lin Wu, 2 Jean-Louis Pujol, 13 Hiroyuki to, 4Cinthya Coronado Erdmann, 15 Padma Sathyanarayana,¹⁵ Stephanie Meadows- Shropshire, 15 Mariano Provencio Pulla The University of Texas 0 Anderson Cancer Center, Houston, TX, USA; Dana-Farber Cancer include, Boston, MA, MA, McGC invests ind Certa, fortnal, Quebec, Canada; National Cancer Center National Clinical Research Center for Cancer Cancer Hospital, Chinese licademy of Medical Sciences and Pairy - Medical College, Beljing, China; Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai lac Tong University, Stanghal, China; University If Occupational and Environmental Health, Kitakyushu, Japan; The Bloomberg Kinnel institute for Cancer Innuratheripy, kin Hopkins Driversity School X Medcine, latinor, MD, USA; Erasmus MC Cancer Institute, Rotterdam, Netherlands; Thomayer Hospital, Poese, Card Republic John Paul I Hospital, Injoice, Poland, University, Prague, Czech Republic; Hum Cancer Hospital, Changsha, Chinac Regional Diversity Hospital, Martpeller, France, Cancer Center, Yokohama, Japan; Bristol Myers Squibb, Princeton, NJ, USA; Hospital eta de Herra, Kadrid, Spain Presentation number LBA1 --- [Slide 2] CheckMate 77T: perioperative NIVO in resectable NSCLC EFS by baseline disease stage Stage II Stage III NIVO + chemo/NIVO Chemo/PBO NIVO + chemo/NIVO Chemo/PBO (n = 81) (n = 81) (n = 148) (n = 149) Median EFS, mo NR NR Median EFS, mo 30.2 (95% CI) 13.4 (22.6-NR) (24.2-NR) (95% CI) (26.9-NR) (9.8-17.7) HR (95% CI) 0.81 (0.46-1.43) HR (95% CI) 0.51 (0.36-0.72) 100 100 80 78% 80 71% NIVO + chemo/NIVO 73% 60 60 EFS (%) NIVO + chemo/NIVO Chemo/PBO EFS (%) 52% 40 40 20 20 Chemo/PBO 0 0 0 6 12 18 24 30 36 42 0 6 12 18 24 30 36 Months from randomization Months from randomization t risk 62 49 37 20 5 2 0 148 111 92 78 49 15 2 NIVO 81 PBO 81 63 51 34 20 8 2 0 149 102 67 44 24 11 4 w-up (range): 25.4 months (15.7-44.2). --- [Slide 3] CheckMate 77T: perioperative NIVO in resectable NSCLC Exploratory analysis: EFS by pCR and MPR status EFS by pCR EFS by MPR 100 100 NIVO + chemo/NIVO (pCR) 80 NIVO chemo/NIVO (MPR) 80 Chemo/PBO (MPR) 60 Chemo/PBO (pCR) 60 EFS (%) NIVO + chemo/NIVO (no pCR) EFS (%) 40 40 HR (95% CI) HR (95% CI) NIVO . chemo/NIVO (no MPR) NIVO + chemo/NIVO Chemo/PBO (no pCR) NIVO + chemo/NIVO 20 20 vs chemo/PBO Chemo/PBO (no MPR) vs chemo/PBO pCRᵃ 0.33 (0.08-1.37) MPRᵇ 0.40 (0.16-0.99) No pCRᵃ 0.79 (0.58-1.06) No MPR 0.85 (0.62-1.15) 0 0 0 6 12 18 24 30 36 42 0 6 12 18 24 30 36 42 Months from randomization Months from randomization lo. at risk 76 70 59 37 8 1 0 pCR 58 56 53 45 28 4 0 0 MPR 81 pCR 11 11 11 11 5 2 1 0 MPR 28 27 23 20 10 5 1 0 71 56 32 12 3 0 No pCR 171 117 88 70 41 16 4 0 No MPR 148 97 No pCR 221 154 107 67 39 17 5 0 No MPR 204 138 95 58 34 14 5 0 HR (95% CI), 0.14 (0.06-0.35) in patients with pCR vs those without in the NIVO + chemo/NIVO arm and 0.32 (0.10-1.00) in the chemo/PBO arm. HR (95% CI), 0.18 (0.09-0.35) in patients with MPR vs those without in the Median follow-up (range): 25.4 months (15.7-44.2). NIVO + chemo/NIVO arm and 0.40 (0.20-0.78) in the chemo/PBO arm. --- [Slide 4] CheckMate 77T: perioperative NIVO in resectable NSCLC Summary Neoadjuvant NIVO + chemo followed by surgery and adjuvant NIVO demonstrated statistically significant and clinically meaningful EFS improvement VS chemo/PBO in patients with resectable NSCLC (HR, 0.58; P = 0.00025) — EFS benefit was seen across most key subgroups pCR and MPR rates were also improved: 25.3% vs 4.7% and 35.4% vs 12.1%, respectively In an exploratory analysis, perioperative NIVO favored EFS in patients with a pCR following neoadjuvant therapy, with a trend toward improved EFS in patients without a pCR Among patients eligible for adjuvant therapy, perioperative NIVO improved EFS vs chemo/PBO, regardless of pCR status - Neoadjuvant NIVO + chemo continued to provide benefit over chemo in patients who were unable to receive adjuvant therapy Perioperative NIVO-based regimen showed no new safety signals. Surgical feasibility was similar between treatment arms CheckMate 77T is the first phase 3 perioperative study to build on the SOC neoadjuvant NIVO + chemo and supports perioperative NIVO as a potential new treatment option for patients with resectable NSCI

[Slide 1] E SNINKER MIASON SVR AUTHAR and

[Slide 1] Perioperative vs neoadjuvant NIVO: Patient-level analysis Methods: perioperative NIVO vs neoadjuvant NIVO + chemo Surgery Analysis patient populations CheckMate 816¹ Neoadjuvant NIVO + chemo (3 cycles) Patients who had surgery CheckMate 77T2 Neoadjuvant NIVO + chemo Patients who had surgery and (up to 4 cycles) received ≥ 1 dose of adjuvant NIVO Endpoint EFS (BICR) landmarked from time of surgery In lieu of a head-to-head trial, exploratory propensity score weighting analyses (ATT and ATEᵇ) were performed to allow simplified reproduction of a randomized trial by adjusting for clinically relevant baseline demographics and disease characteristics between study populations and reducing the confounding effects of these factors — Subgroup analyses were not weighted due to smaller sample sizes Median duration of follow-upd: 29.5 months (CheckMate 816) and 33.3 months (CheckMate 77T) *Average treatment effect for the treated (ATT): a weight of 1 was applied to patients in the perioperative NIVO arm of CheckMate 777; varying weights were applied to patients in the CheckMate $16 NIVO . chemo arm to make them comparable to those in the perioperative NIVO arm in CheckMate 77T based on propensity scores. *Average treatment effect (ATE): varying weights were applied to all patients in the populations of interest from CheckMate 77T and CheckMate 816 to make them comparable to one another based on propensity scores. Sex, race. clinical stage, tumor histology. PD-L1 expression. age. ECOG PS. and smoking status. Database locks: CheckMate 816, October 20, 2021: CheckMate 77T. April 26, 2024. 1. Forde PM, et al. N Engl J Med 2022:386:1973-1985. 2. Cascone T, et at N Engl J Med 2024:390:1756-1769. --- [Slide 2] Perioperative vs neoadjuvant NIVO: Patient-level analysis Landmark EFS (BICR) from definitive surgery 100 80 Periop NIVOᵃ (CheckMate 77T) 60 EFS (%) Weighted (ATE)ᵇ 40 Neoadj NIVO + chemo Periop Neoadj (CheckMate 816) NIVOᵃ NIVO + chemo 20 (n = 139.4°) (n = 147.5°) HR (95% CI) 0.61 (0.39-0.97) 0 0 6 12 18 24 30 36 42 48 Months from surgery No. at risk Periop NIVO 139.4 128.0 118.1 112.9 79.7 42.5 13.0 3.1 0 Neoad) N+C 147.5 121.0 106.2 84.2 39.1 12.1 2.2 0 0 HR (95% CI): ATTd weighted analysis, 0.56 (0.35-0.90); unweighted analysis, 0.59 (0.38-0.92) Median follow-up: CheckMate 816. 29.5 months: CheckMate 777. 33.3 months. *Includes only patients who received : 1 dose of adjuvant NIVO. PATE: varying weights were applied to all patients in both neoadjuvant NIVO . chemo acm (CheckMate 816) and perioperative NIVO (CheckMate 77T) to make them comparable to one another. N values fractional due to weighting. ATT: varying weights were applied to patients in the neoadjuvant NIVO chemo arm (CheckMate 816) to make them comparable to those in the perioperative NIVO arm (CheckMate 777). in the unweighted analysis population, 89 patients (64%) completed adjuvant therapy. and median number of doses (range) was 13.0 (1-13). Unwerighted landmark EFS from surgery among all patients who had surgery (regardless of whether they received adjuvant NIVO in CheckMate 777) for period NIVO v: necad) NIVO - chemo: HR - 0.82 (95% CI, 0.55-1.21). --- [Slide 3] Perioperative VS neoadjuvant NIVO: Patient-level analysis Landmark EFSa (analysis population) by pCR statusᵃ,b pCRᶜ No pCR 100 100 80 80 EFS (%) 60 EFS (%) 60 40 40 Periop Neoadj Periop Neoadj 20 NIVOd NIVO + chemo 20 NIVOd NIVO + chemo (n = 50) (n = 43) (n = 73) (n = 96) HR (95% CI) 0.58 (0.14-2.40) HR (95% CI) 0.65 (0.40-1.06) 0 0 0 6 12 18 24 30 36 39 0 6 12 18 24 30 36 42 48 No. at risk Months from surgery Months from surgery Periop NIVO 50 50 48 47 36 18 4 0 73 62 55 53 35 22 8 4 0 Neoadj N+C 43 40 39 35 19 6 2 0 96 75 60 47 19 7 1 0 0 Median follow-up: CheckMate 816, 29.5 months; CheckMate 77T, 33.3 months. Patients with non-evaluable pCR status were excluded. Unweighted analyses. PCR rates in this analysis population: perioperative NIVO, 40.7%; neoadjuvant NIVO - chemo, 30.5% Includes only patients who received : 1 dose of adjuvant NIVO. --- [Slide 4] Perioperative vs neoadjuvant NIVO: Patient-level analysis Landmark EFS (analysis population) by tumor PD-L1 expressionᵃ,ᵇ PD-L1 < 1% PD-L1 ≥ 1% 100 100 80 80 EFS (%) 60 EFS (%) 60 40 40 Periop Neoadj Periop Neoadj 20 NIVOc.d NIVO + chemo 20 NIVOᶜ,d NIVO + chemo (n = 53) (n = 63) (n = 80) (n = 74) HR (95% CI) 0.51 (0.28-0.93) HR (95% CI) 0.86 (0.44-1.70) 0 0 0 6 12 18 24 30 36 42 48 0 6 12 18 24 30 36 42 48 Months from surgery Months from surgery No. at risk Periop NIVO 53 48 43 40 27 15 7 1 0 80 74 68 66 48 26 6 2 0 Neoad) N.C 63 49 39 29 15 6 2 0 0 74 $ 61 53 24 7 1 0 0 Median follow-up: CheckMate 816, 29.5 months; CheckMate 77T, 33.3 months. Patients with non-evaluable PD-L1 expression were excluded. Unweighted analyses. Includes only patients who received 21 dose of adjuvant NIVO. Completed adjuvant treatment: - 1%, 33 patients (62%) and 2 1%, 51 patients (64%). Median number of doses (range): 1%, 13 (1-13) and 2 1%, 13 (1-13).