CheckMate-142 Study Design

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1 Nivolumb + Ipilimumb Combintion in Ptients With DNA Mismtch Repir-Deficient/Microstellite Instbility-High Metsttic Colorectl Cncer: First Report of the Full Cohort From CheckMte-142 Thierry André, 1 Sr Lonrdi, 2 K Yeung Mrk Wong, 3 Heinz-Josef Lenz, 4 Fbio Gelsonimo, 5 Mssimo Agliett, 6 Michel Morse, 7 Eric Vn Cutsem, 8 Ry McDermott, 9 Andrew Grhm Hill, 10 Michel B. Swyer, 11 Alin Hendlisz, 12 Brt Neyns, 13 Mgli Svrcek, 1 Rebecc A. Moss, 14 Jen-Mrie Ledeine, 15 Z. Alexnder Co, 14 Shitl Kopetz, 16 Michel J. Overmn 16 1 Hôpitl Sint Antoine nd Sorbonne Universités, UMPC Pris 06, Pris, Frnce; 2 Istituoto Oncologico Veneto IOV-IRCSS, Pdov, Itly; 3 The University of Sydney, Sydney Medicl School, Sydney, Austrli; 4 University of Southern Cliforni Norris Comprehensive Cncer Center, Los Angeles, CA; 5 University Hospitl of Moden, Itly; 6 University of Torino, Turin, Itly; 7 Duke University Office of Reserch Administrtion, Durhm, NC; 8 University Hospitls Gsthuisberg-Leuven, Leuven, Belgium; 9 St Vincent s University Hospitl, Dublin, Irelnd; 10 Tsmn Oncology Reserch Pty Ltd, Southport, Queenslnd, Austrli; 11 Cross Cncer Institute, Edmonton, AB, Cnd; 12 Institut Jules Bordet, Brussels, Belgium; 13 Universitir Ziekenhuis Brussel, Brussels, Belgium; 14 Bristol-Myers Squibb, Princeton, NJ; 15 Bristol-Myers Squibb, Brine-l Alleud, Belgium; 16 MD Anderson Cncer Center, Houston, TX

2 CheckMte-142 Study Design Phse 2 Nonrndomized Study Histologiclly confirmed metsttic or recurrent CRC dmmr/msi-h per locl lbortory 1 prior line of therpy Combintion cohort Monotherpy cohort Nivolumb 3 mg/kg + ipilimumb 1 mg/kg Q3W (4 doses nd then nivolumb 3 mg/kg Q2W) Nivolumb 3 mg/kg Q2W Primry endpoint: ORR per investigtor ssessment (RECIST v1.1) Other key endpoints: ORR per BICR, DCR, b, DOR, PFS, OS, nd sfety Medin follow-up in the combintion therpy cohort (N = 119) ws 13.4 months (rnge, 9-25) c Results of the monotherpy cohort (N = 74) with similr medin follow-up of 13.4 months (rnge, 10-32) re lso presented 1,c Enrollment ws stggered with dditionl ptients being enrolled if 7 of the first 19 centrlly confirmed MSI-H ptients hd confirmed response (CR or PR). CheckMte-142 monotherpy nd comintion therpy; Cohorts were not rndomized or designed for forml comprison. b Ptients with CR, PR, or SD for 12 weeks. c Defined here s the time from first dose to dt cutoff. 1. Overmn MJ, et l. Lncet Oncol2017;18;

3 Investigtor-Assessed Response nd Disese Control DCR b ws 80% (95% CI: 71.5, 86.6) with combintion therpy nd 69% (57.1, 79.2) with monotherpy 1,d Combintion therpy provided numericlly higher ORR, including CRs, nd DCR reltive to monotherpy during similr follow-up period d Medin follow-up ws 13.4 months (rnge, 9-25). b Disese control defined s ptients with CR, PR, or, SD for 12 weeks. c Medin follow-up ws 13.4 months (rnge, 10-32). d CheckMte-142 monotherpy nd combintion therpy cohorts were not rndomized or designed for forml comprison. 1. Overmn MJ t l. LncetOncol2017;18;

4 Chrcteriztion of Response Nivolumb + ipilimumb Medin time to response ws 2.8 months (rnge, 1-14) Responses were durble: - Medin DOR ws not reched - 94% of responders hd ongoing responses t dt cutoff Response per investigtor ssessment.

Response nd Disese Control in Ptient Subsets Nivolumb + ipilimumb (N = 119) n ORR DCR b Tumor PD-L1 expression, n(%) 1% 26 14 (54) 20 (77) < 1% 65 34 (52) 51 (78) BRAFI/KRAS muttion sttus, n (%) Wild

5 Response nd Disese Control in Ptient Subsets Nivolumb + ipilimumb (N = 119) n ORR DCR b Tumor PD-L1 expression, n(%) 1% (54) 20 (77) < 1% (52) 51 (78) BRAFI/KRAS muttion sttus, n (%) Wild type (55) 24 (77) BRAF mutnt (55) 23 (79) KRAS mutnt (57) 37 (84) Clinicl history of Lynch syndrome, n (%) c Yes (71) 30 (86) No (48) 25 (81) 0 Responses were observed irrespective of tumor PD-L1 expression, BRAF or KRAS muttionl sttus, or clinicl history of Lynch syndrome Per investigtor ssessment. b Ptients with CR, PR, or SD for 12 weeks. c Bsed on the clinicl records of the ptients t sites in countries where this reporting ws permitted (excluded Itly).

6 Progression-Free nd Overll Survivl Nivolumb + Ipilimumb,b 9-month rte (95% CI), % 76 (67.0, 82.7) 12-month rte (95% CI), % 71 (61.4, 78.7) Nivolumb + Ipilimumb,b 9-month rte (95% CI), % 87 (80.0, 92.2) 12-month rte (95% CI), % 85 (77.0, 90.2) With similr follow-up, combintion therpy provided improved PFS nd OS reltive to monotherpy Medin follow-up ws 13.4 months (rnge, 9-25). b Medin PFS ws not reched (95% CI, not estimble). c PFS per investigtor ssessment. d Medin OS ws not reched (95% CI, 18.0, not estimble). e Medin follow-up ws 13.4 months (rnge, 10-32). f CheckMte-142 monotherpy nd combintion therpy cohorts were not rndomized or designed for forml comprison. 1. Overmn MJ, et l. LncetOncol2017;18;

7 Qulity of live Nivolumb + ipilimumb Sttisticlly significnt nd cliniclly meningful improvements were chieved in key qulity of life mesures, with improvements mintined for extended periods while on tretment EORTC = Europen Orgnistion for Reserch nd Tretment of Cncer; QoL = Qulity of Life; VAS = visul nlog scle. Chnges in men scores over time were nlyzed using liner mixed models djusted for bseline score. Chnges from bseline of 10 points (EORTC QLQ-C30) nd 7 points (EQ-5D VAS) were regrded s cliniclly meningful. 1,2 1. Osob D, et l. J Clin Oncol 1998;16; Pickrd AS, et l. Helth Qul Life Outcomes 2007;5;70.

8 Conclusions: Nivolumb + ipilimumb provided durble clinicl benefit in previously treted ptients with dmmr/msi=h mcrc - High ORR (55%) nd durble responses (medin DOR not reched) - Medin PFS nd OS not reched with medin follow-up of 13 months; 85% of ptients live t 1 yer Meningful improvements in qulity of life were observed Sfety ws mngeble with low rte of discontinution due to TRAEs Indirect comprisons in CheckMte-142 suggest tht nivolumb + ipilimumb provides improved clinicl benefit reltive to nivolumb monotherpy Nivolumb + ipilimumb represents promising new tretment option for ptients with previously treted dmmr/msi-h mcrc

9 Nivolumb in Ptients with DNA Mismtch Repir-Deficient / Microstellite Instbility-High Metsttic Colorectl Cncer: Long-Term Survivl According to Prior Line of Tretment From CheckMte-142 Michel J. Overmn, 1 Frncesc Bergmo, 2 Ry McDermott, 3 Mssimo Agliett, 4 Frnklin Chen, 5 Fbio Gelsomino, 6 K Yeung Mrk Wong, 7 Michel Morse, 8 Eric Vn Cutsem, 9 Alin Hendlisz, 10 Brt Neyns, 11 Rebecc A. Moss, 12 Hunyu Zho, 12 Z. Alexnder Co, 12 Shitl Kmble, 12 Scott Kopetz, 1 Thierry André 13 1 MD Anderson Cncer Center, Houston, TX; 2 Istituto Oncologico Veneto IRCSS, Pdov, Itly; 3 St. Vincent s University Hospitl, Dublin, Irelnd; 4 University of Torino, Turin, Itly; 5 Novnt Helth Oncology Specilists, Winston-Slem, NC; 6 University Hospitl of Moden, Moden, Itly; 7 The University of Sydney, Sydney Medicl School, Sydney, Austrli; 8 Duke University Office of Reserch Administrtion, Durhm, NC; 9 University Hospitls Gsthuisberg Leuven, Leuven, Belgium; 10 Institut Jules Bordet, Brussels, Belgium; 11 Universitir Ziekenhuis Brussel, Brussels, Belgium; 12 Bristol-Myers Squibb, Princeton, NJ; 13 Hôpitl Sint Antoine nd Sorbonne Universités, UMPC Pris 06, Pris, Frnce

10 CheckMte-142 Monotherpy Cohort Study Design Histologiclly confirmed metsttic or recurrent CRC dmmr/msi-h per locl lbortory 1 prior line of therpy Monotherpy cohort Nivolumb 3 mg/kg Q2W Primry endpoint: ORR per investigtor ssessment Other key endpoints: ORR per BICR, DCR, b DOR, PFS, OS, nd sfety Primry nlysis (N = 74): efficcy per BICR nd sfety; medin follow-up, 21 months (rnge, 17-40) c Subset nlysis: Group A (n = 53): received 3 prior chemotherpies, including fluoropyrimidine, oxlipltin, nd irinotecn Group B (n = 21): did not receive prior tretment with ll 3 of these chemotherpies (fluoropyrimidine, oxlipltin, nd irinotecn) DCR = disese control rte Enrolment ws stggered with dditionl ptients being enrolled if 7 of the first 19 centrlly confirmed MSI-H ptients hd confirmed response (CR or PR). b Ptients with CR, PR, or SD for 12 weeks. c Time from first dose to dt cutoff.

11 Response, Disese Control, nd Durbility All ptients N = 74 ORR, n (%) [95% CI] Best overll response, n (%) CR PR SD PD Unble to determine Disese control, n (%) d [95% CI] 25 (34) [23.2, 45.7] 7 (9) 18 (24) 23 (31) 22 (30) 4 (5) 46 (62) [50.1, 73.2] Medin DOR (rnge), months NR (1.4+ to 31.6+) Medin durtion of SD (rnge), months 8.3 (4.2, NE) Medin time to response ws pproximtely 2.8 months cross ll groups Clinicl benefit ws observed cross ll groups NE= non estimble; NR not reched BICR dt with medin follow-up of 21 months (rnge, 17-40). b Group A ptients received 3 prior chemotherpies including fluoropyrmidine, oxlipltin, nd irinotecn. c Group B ptients did not receive prior Tretment with ll 3 of these chemotherpies (fluoropyrmidine, oxlipltin nd irinotecn). d Ptients with CR, PR, or SD for 12 weeks.

12 Chrcteriztion of Response: All Ptients Responders with Nivolumb Nivolumb continued to provide cliniclly meningful nd durble responses - 80% of responders hd ongoing responses t dt cutoff - 64% hd responses lsting 12 months BICR dt with medin follow-up of 21 months (rnge, 17-40).

13 Progression-Free Survivl: All Ptients Medin PFS (95% CI), months PFS rte (95% CI), % 12 months 18 months All ptients N = (3.0, NE) 44 (32.6, 55.3) 44 (32.6, 55.3) Medin PFS ws 4.2 months nd not reched in groups A nd B, respectively b 12- nd 18-month PFS rtes were 41% (group A) nd 52% (group B) b NE, not estimble. BICR dt with medin follow-up of 21 months. b Group A ptients received 3 prior chemotherpies, including fluoropyrimidine, oxlipltin, nd irinotecn. Group B ptients did not receive Prior tretment with ll 3 these chemotherpies (fluoropyrmidine, oxlipltin, nd irinotecn).

14 Overll Survivl: All Ptients Medin OS (95% CI), months OS rte (95% CI), % 12 months 18 months All ptients N = 74 NR (19.6, NE) 72 (60.0, 80.9) 67 (54.9, 76.9) Medin OS ws not reched in groups A or B 12-month OS rte ws 68% (group A) nd 81% (group B) 18-month OS rte ws 66% (group A) nd 70% (group B) NE = not estimble; NR = not reched Group A ptients received 3 prior chemotherpies, inluding fluoropyrmidine, oxlipltin, nd irinotecn. Group B ptients did not receive prior tretment with ll 3 of these chemotherpies (fluoropyrmidine, oxlipltin nd irinotecn).

15 Overll Survivl by Best Overll Response Medin OS (95% CI), months CR + PR n = 25 SD n = 23 PD n = 22 NR (NE) NR (14.3, NE) 10.3 (3.0, NE) Best overll response to nivolumb tretment correlted with overll survivl. NE = not estimble, NR not reched.

16 Conclusions: Nivolumb continued to provide durble clinicl benefit with long-term follow-up (21 months) in previously treted ptients with dmmr/msi-h mcrc - PFS nd OS rtes demonstrted continued stbility - CR rte incresed with longer follow-up - Medin DOR nd OS were not reched Durble clinicl benefit with deepening of response ws observed regrdless of prior chemotherpy with fluoropyrmidine, oxlipltin, nd irinotecn No new sfety signls were reported with long-term follow-up Results support ongoing evlution of nivolumb-bsed therpy in the first-line setting

Introduction. These patients benefit less from conventional chemotherapy than patients identified as MMR proficient or microsatellite stable 3-5

Introduction. These patients benefit less from conventional chemotherapy than patients identified as MMR proficient or microsatellite stable 3-5 Nivolumb + Ipilimumb Combintion in Ptients With DNA Mismtch Repir-Deficient/Microstellite Instbility-High Metsttic Colorectl Cncer: First Report of the Full Cohort From CheckMte-142 Abstrct 553 André T,