OVERALL SURVIVAL IN KATE2 (NCT02924883): A PHASE 2 STUDY OF PD-L1 - PowerPoint PPT Presentation

OVERALL SURVIVAL IN KATE2 (NCT02924883): A PHASE 2 STUDY OF PD-L1 INHIBITOR ATEZOLIZUMAB + TRASTUZUMAB EMTANSINE (T-DM1) VS PLACEBO + T-DM1 IN PREVIOUSLY TREATED HER2-POSITIVE ADVANCED BREAST CANCER Leisha A. Emens , 1 Francisco Esteva, 2 Mark Beresford, 3 Cristina Saura, 4 Michelino De Laurentiis, 5 Sung-Bae Kim, 6 Seock-Ah Im, 7 Yifan Wang, 8 Aruna Mani, 9 Jigna Shah, 9 Haiying Liu, 9 Sanne de Haas, 10 Monika Patre, 10 Sherene Loi 11 1 University of Pittsburgh Medical Center Hillman Cancer Center, Pittsburgh, PA; 2 Perlmutter Cancer Center at NYU Langone Medical Center, New York, NY; 3 Royal United Hospital, Bath, UK; 4 Vall d’Hebron University Hospital, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain; 5 IRCCS Istituto Nazionale Tumori Fondazione Pascale, Napoli, Italy; 6 Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea; 7 Seoul National University Hospital, Seoul, Korea; 8 Roche (China) Holding Ltd, Shanghai, China; 9 Genentech, Inc., South San Francisco, CA; 10 F. Hoffmann-La Roche, Basel, Switzerland; 11 Peter MacCallum Cancer Centre, Melbourne, Australia esmo.org Access slides at: https://bit.ly/2NGiaqZ

DISCLOSURES Advisory roles: AbbVie, Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb, Celgene, Genentech, Gritstone, Lilly, Macrogenics, Medimmune, Molecuvax, Novartis, Peregrine, Replimune, Roche, Syndax, Vaccinex Royalties: Aduro Biotech Grants: Aduro Biotech, AstraZeneca, Breast Cancer Research Foundation Stocks: None Others: Research funding: Aduro Biotech, AstraZeneca, Breast Cancer Research Foundation, Corvus, Department of Defense, EMD Serono, Genentech, HeritX, Inc., Maxcyte, Merck, National Cancer Institute, NSABP Foundation, Roche, Translational Breast Cancer Research Consortium Access slides at: https://bit.ly/2NGiaqZ

KATE2: BACKGROUND Atezolizumab: • T-DM1 is indicated for the treatment of HER2-positive Promotes T-cell metastatic breast cancer previously treated with trastuzumab Activated activation T cells and a taxane • In addition to its cytotoxic activity, T-DM1 may potentiate DC tumour immunity Tumour cells • Combining T-DM1 with atezolizumab, an anti-PD-L1 antibody Tumour that restores anti-cancer immunity, 1,2 may result in greater T-DM1: Targets antigen the HER2 s clinical activity than either drug alone receptor and promotes • In KATE2 (NCT02924883), there was no statistically significant tumour cell death difference in PFS in patients with HER2-positive advanced breast cancer treated with atezolizumab + T-DM1 vs placebo + Atezolizumab: Restores T-DM1 in the ITT population (median PFS 8.2 vs 6.8 m), but anti-cancer immunity, with activity further PFS was numerically longer with combination treatment in enhanced by patients with PD-L1 IC+ disease (median PFS 8.5 vs 4.1 m) 3 chemotherapy-induced antigen exposure • Here we present the final analysis of safety and clinical activity 1. Chen DS, Mellman I. Immunity 2013;39:1-10; 2. Herbst RS, et al. Nature. 2014;515:563-567; 3. Emens LA, et al. San Antonio Breast Cancer Symposium; Access slides at: https://bit.ly/2NGiaqZ Dec 4-8, 2018; San Antonio, TX. Abstract PD3-01. DC, dendritic cell; IC, tumour-infiltrating immune cell; ITT, intention-to-treat.

KATE2: STUDY DESIGN Efficacy endpoints in the ITT population Primary endpoint : • Investigator-assessed PFS HER2+ LABC or MBC Secondary endpoints: Until loss of T-DM1 3.6 mg/kg q3w • Prior taxane and clinical • OS + benefit trastuzumab Survival Follow-Up • Objective response rate Atezolizumab 1200 mg • Progression on • Duration of response 2 q3w metastatic therapy Exploratory endpoints: or within 6 months R of adjuvant therapy • PFS in patients with PD-L1+ 1 RECIST 1.1 T-DM1 3.6 mg/kg q3w • Measurable Until PD disease + per disease • Exploratory biomarker Placebo 1200 mg q3w subgroups (PD-L1, PIK3CA (n=202) mutation status, HER2 expression, immune-related Stratification factors: [TILs, CD8 IHC expression]) • Tumour PD- L1 IC status (IC0 [<1%] vs IC1/2/3 [≥1%]) a Post hoc endpoint: • World region (Western Europe vs North America vs rest of world) • OS in PD-L1 subgroups • Presence of liver metastases (yes or no) • Data cutoff for primary analysis: 11 December 2017 a Determined using VENTANA SP142. • Data cutoff for OS analysis: 11 December 2018 Access slides at: https://bit.ly/2NGiaqZ IC, tumour-infiltrating immune cell; IHC, immunohistochemistry; ITT, intention-to-treat; LABC, locally advanced breast cancer; MBC, metastatic breast cancer; OS, overall survival; PD, progressive disease; PFS, progression-free survival; TIL, tumour-infiltrating lymphocyte.

PRIMARY ANALYSIS RESULTS OF KATE2: PFS IN ITT AND PD-L1 IC+ POPULATIONS ITT PD-L1 IC+ Median PFS (range) Median PFS (range) 100 100 T-DM1 + atezolizumab: 8.2 mo (5.8–10.7) T-DM1 + atezolizumab: 8.5 mo (5.7–NE) T-DM1 + placebo: 6.8 mo (4.0–11.1) T-DM1 + placebo: 4.1 mo (2.7–11.1) Stratified HR=0.82 (95% CI: 0.55–1.23) Stratified HR=0.60 (95% CI: 0.32–1.11) 80 80 P =0.3332 6-month PFS rate PFS Rate (%) PFS Rate (%) 60 58% 60 12-month PFS rate 51% 38% 40 40 34% 20 20 T-DM1 + Atezolizumab (n=133) T-DM1 + Atezolizumab (n=57) T-DM1 + Placebo (n=69) T-DM1 + Placebo (n=27) 0 0 0 2 4 6 8 10 12 14 0 2 4 6 8 10 12 14 Months Months No. of Patients at Risk No. of Patients at Risk T-DM1 + Atezolizumab 133 131 118 100 90 74 59 46 42 26 25 21 15 3 T-DM1 + Atezolizumab 57 56 51 44 40 31 24 19 16 9 9 8 6 2 T-DM1 + Placebo 69 66 54 46 42 33 31 25 23 18 15 14 7 1 T-DM1 + Placebo 27 26 20 16 15 11 10 9 8 7 6 6 1 Emens LA, et al. San Antonio Breast Cancer Symposium; Dec 4-8, 2018; San Antonio, TX. Abstract PD3-01. Access slides at: https://bit.ly/2NGiaqZ HR, hazard ratio; IC, tumour-infiltrating immune cell; ITT, intention-to-treat; NE, not estimable; PFS, progression-free survival. 11 December 2017 cutoff date

KATE2: BASELINE DEMOGRAPHICS T-DM1 + T-DM1 + T-DM1 + T-DM1 + Atezolizumab Placebo Atezolizumab Placebo (n=133) (n=69) (n=133) (n=69) PD-L1+ disease a Hormone receptor status 57 (43%) 27 (39%) ER− and PR− 48 (36%) 29 (42%) Median age, y (range) 54 (29–78) 55 (28–77) Aged <65 y 118 (89%) 58 (84%) ER+ and/or PR+ 79 (59%) 38 (55%) Unknown 6 (5%) 2 (3%) Sex, female 131 (98%) 69 (100%) Prior lines of therapy for MBC Race 0 15 (11%) 6 (9%) White 72 (54%) 44 (64%) 1 68 (51%) 40 (58%) Asian 49 (37%) 23 (33%) 2 23 (17%) 9 (13%) Other 12 (9%) 2 (3%) ≥3 27 (20%) 14 (20%) ECOG PS b 0 93 (70%) 40 (58%) a Positive defined as IHC IC 1/2/3. b There was one patient with unknown ECOG status in each study arm. 1 39 (29%) 28 (41%) Liver metastases 44 (33%) 22 (32%) Visceral involvement 95 (71%) 48 (70%) ECOG PS, Eastern Cooperative Oncology Group performance status; Access slides at: https://bit.ly/2NGiaqZ ER, oestrogen receptor; MBC, metastatic breast cancer; PR, progesterone receptor.

KATE2: PATIENT DISPOSITION IN THE ITT POPULATION T-DM1 + Atezolizumab T-DM1 + Placebo (n=133) (n=69) On-study, as of data cutoff date 81 (61%) 35 (51%) (11 December 2018) Alive on study treatment 25 (19%) 8 (12%) Alive in survival follow-up 56 (42%) 27 (39%) Discontinued study 52 (39%) 34 (49%) Death a 29 (22%) 18 (26%) Withdrawal by subject 21 (16%) 15 (22%) Other b 2 (2%) 1 (1%) a Some patients agreed to provide survival status after withdrawal from the study, so the number of patients who discontinued from study due to death is smaller than the total number of deaths. b One protocol deviation, one lost to follow-up, one other. ITT, intention-to-treat. Access slides at: https://bit.ly/2NGiaqZ

KATE2: OS IN ITT POPULATION 100 T-DM1 + Atezolizumab (n=133) T-DM1 + Placebo (n=69) Censored 80 Overall Survival (%) 60 40 T-DM1 + T-DM1 + Atezolizumab Placebo Median follow -up (mo) 19.0 18.2 Patients w ith OS event, n (%) 32 (24.1) 20 (29.0) 20 Median OS (mo) NE NE Stratified HR (95% CI) 0.74 (0.42–1.30) 1-year survival rate (%) 89.1 89.0 0 0 3 6 9 12 15 18 21 24 27 Time (mo) No. of Patients at Risk T-DM1 + Atezolizumab 133 131 130 129 126 122 122 121 118 116 116 114 111 111 104 101 98 86 78 66 56 44 42 34 21 6 T-DM1 + Placebo 69 67 66 64 63 62 61 61 60 58 55 54 54 51 48 47 45 37 35 29 23 16 14 12 8 1 • With 52 OS events reported, median OS was not reached in either arm • 1-year OS was similar in both arms Access slides at: https://bit.ly/2NGiaqZ CI, confidence interval; HR, hazard ratio; NE, not estimable; ITT, intention-to-treat; OS, overall survival. 11 December 2018 cutoff date