Astrazeneca Plc · LSE:AZN
Astrazeneca — ASCO GI Cancers Symposium 2022 investor science conference call
42 slides from Astrazeneca's conference presentation, Jan 24, 2022
Slide 1: Investor science conference call: ASCO GI Cancers Symposium 2022
Investor science conference call: American Society of Clinical Oncology Gastrointestinal (ASCO GI) Cancers Symposium 2022 Conference call for investors and analysts 24 January 2022
Slide 2: Forward-looking statements
Forward-looking statements In order, among other things, to utilise the 'safe harbour' provisions of the US Private Securities Litigation Reform Act of 1995, AstraZeneca (hereafter ‘the Group’) provides the following cautionary statement: this document contains certain forward-looking statements wit
Slide 3: Speakers
Dr Bruno Sangro Dr Arndt Vogel Investigator, HIMALAYA and Steering Committee member, Professor – Head Liver Unit and TOPAZ-1 and Professor - HPB Oncology Area, Clinica Department of Gastroenterology, Universidad de Navarra Hepatology and Endocrinology, Hannover Medical School Susan Galbraith Dave Fr
Slide 4: Agenda
1 Introduction: AstraZeneca @ ASCO GI 2022 Agenda 2 Imfinzi Phase III TOPAZ-1 trial 3 Imfinzi + tremelimumab Phase III HIMALAYA trial 4 Commercial opportunity 5 What’s next for AstraZeneca in GI? 6 Closing and Q&A 4
Slide 5: Introduction
1 Introduction Susan Galbraith Executive Vice President, Oncology R&D
Slide 6: Comprehensive portfolio to combat cancer
Comprehensive portfolio to combat cancer Diverse pipeline with potential for orthogonal combinations Tumour drivers Oncogenic truncal drivers Redirect local immunity Immune and resistance and mechanisms of resistance Awaken dormant immune cells engagers DNA damage Synthetic lethality response exploi
Slide 7: ASCO GI 2022 abstracts and data highlights
ASCO GI 21 abstracts with Data 2022 Four oral presentations highlights • Imfinzi +/- tremelimumab • Two Proffered paper oral in HCC presentations (late HIMALAYA breakers) Study 22 • Two Mini oral presentations • Imfinzi in BTC TOPAZ-1 • 17 Posters • Enhertu • 21 Abstracts DESTINY-Gastric01, DESTINY-
Slide 8: Imfinzi and tremelimumab
Imfinzi and tremelimumab Phase II data in gastrointestinal cancers informed TOPAZ-1 and HIMALAYA designs Study 221 HCC T-cell proliferation data Phase II trial in biliary tract cancer • 121 patients enrolled with 1st-line biliary tract cancer • Imfinzi (+/- tremelimumab) in combination with gemcitab
Slide 9: Imfinzi TOPAZ-1
2 Imfinzi TOPAZ-1 Dr Arndt Vogel Steering Committee Member, TOPAZ-1 Phase III trial
Slide 10: TOPAZ-1 trial design
TOPAZ-1 trial design A double-blind, multicentre, global, Phase III trial Key eligibility • Locally advanced or metastatic BTC (ICC, Durvalumab 1500 mg Q3W + à Durvalumab 1500 mg ECC, GBC) GemCis (up to 8 cycles) Q4W until PD • Previously untreated if unresectable or R (1:1) metastatic at initial di
Slide 11: Patient demographics and baseline characteristics
Patient demographics and baseline characteristics Durvalumab Placebo + GemCis (n=341) + GemCis (n=344) Median age (range), years 64 (20–84) 64 (31–85) Sex, female, n (%) 172 (50.4) 168 (48.8) Race, n (%) Asian 185 (54.3) 201 (58.4) White 131 (38.4) 124 (36.0) Black or African American 8 (2.3) 6 (1.7
Slide 12: Overall survival
Overall survival 12 Median OS Hazard ratio p-value (95% CI), months (95% CI) Durvalumab + GemCis (n=341) 12.8 (11.1–14.0) 0.80 1.0 0.021 Placebo + GemCis (n=344) 11.5 (10.1–12.5) (0.66–0.97) 0.9 Statistical significance cut-off for OS: p=0.03 0.8 0.7 12-mo OS: 18-mo OS: 24-mo OS: Probability of OS 5
Slide 13: Progression free survival
Progression free survival Median PFS Hazard ratio p-value (95% CI), months (95% CI) 1.0 Durvalumab + GemCis (n=341) 7.2 (6.7–7.4) 0.75 0.001 0.9 Placebo + GemCis (n=344) 5.7 (5.6–6.7) (0.63–0.89) 0.8 Statistical significance cut-off for PFS: p=0.0481 0.7 Probability of PFS 0.6 0.5 6-mo PFS: 9-mo PFS
Slide 14: Tumour response
Tumour response ORR* 1.0 DoR‡ 40 Odds ratio: 1.60 0.9 Proportion of patients still in response 35 (95% CI, 1.11–2.31; p=0.011) 0.8 30 0.7 Remaining in Remaining in 25 0.6 response ≥9 mo response ≥12 mo 26.7 0.5 32.6% 26.1% 25.3% ORR, % 20 15.0% 0.4 15 18.7 0.3 10 0.2 5 0.1 0.0 0 Durvalumab + GemCis
Slide 15: Summary of adverse events and treatment exposure
Summary of adverse events and treatment exposure Durvalumab + GemCis (n=338) Placebo + GemCis (n=342) Median duration of exposure (range), months Durvalumab/placebo 7.33 (0.1–24.5) 5.77 (0.2–21.5) Gemcitabine 5.19 (0.1–8.3) 5.03 (0.2–8.6) Cisplatin 5.13 (0.1–8.3) 4.88 (0.2–8.5) Event, n (%) Any AE 3
Slide 16: Conclusions
Conclusions • TOPAZ-1 is the first global Phase III trial to report positive results testing immunotherapy plus chemotherapy as first-line treatment for advanced BTC • TOPAZ-1 met its primary endpoint at the prespecified interim analysis: durvalumab plus GemCis demonstrated statistically significant
Slide 17: Imfinzi + tremelimumab HIMALAYA
3 Imfinzi + tremelimumab HIMALAYA Dr Bruno Sangro Principal Investigator, HIMALAYA Phase III trial
Slide 18: HIMALAYA trial design
HIMALAYA trial design HIMALAYA was an open-label, multicenter, global, Phase III trial Multiple testing procedure Study population T300+D (n=393): • Patients with confirmed uHCC Primary objective OS superiority for T300+D vs Tremelimumab 300 mg × 1 dose + • BCLC B (not eligible for • OS for T300+D v
Slide 19: Baseline characteristics
Baseline characteristics T300+D Durvalumab Sorafenib T300+D Durvalumab Sorafenib Characteristic Characteristic (n=393) (n=389) (n=389) (n=393) (n=389) (n=389) Male sex, n (%) 327 (83.2) 323 (83.0) 337 (86.6) Child-Pugh classification,† n (%) Median age (range), years 65.0 (22–86) 64.0 (20–86) 64.0 (
Slide 20: Overall survival: T300+D versus sorafenib
Overall survival T300+D versus sorafenib T300+D (n=393) Sorafenib (n=389) OS events, n (%) 262 (66.7) 293 (75.3) 1.0 Median OS (95% CI), months 16.4 (14.2–19.6) 13.8 (12.3–16.1) HR (96.02% CI) 0.78 (0.65–0.92) 0.9 p-value (2-sided) 0.0035 0.8 Probability of overall survival 0.7 18-mo OS: 24-mo OS: 3
Slide 21: Overall survival: durvalumab versus sorafenib
Overall survival Durvalumab versus sorafenib Durvalumab (n=389) Sorafenib (n=389) OS events, n (%) 280 (72.0) 293 (75.3) 1.0 Median OS (95% CI), months 16.6 (14.1–19.1) 13.8 (12.3–16.1) 0.9 HR (95.67% CI) 0.86 (0.73–1.03) 0.8 Noninferiority margin=1.08 Probability of overall survival 0.7 0.6 0.5 0.4
Slide 22: Progression free survival
Progression free survival T300+D vs sorafenib PFS for T300+D vs sorafenib T300+D Durvalumab Sorafenib 1.0 (n=393) (n=389) (n=389) Probability of progression-free survival PFS events, n (%) 335 (85.2) 345 (88.7) 327 (84.1) 0.8 Median PFS 3.78 3.65 4.07 (95% CI), months (3.68–5.32) (3.19–3.75) (3.75–5
Slide 23: Safety and tolerability
Safety and tolerability Event, n (%) T300+D (n=388) Durvalumab (n=388) Sorafenib (n=374) Any AE 378 (97.4) 345 (88.9) 357 (95.5) Any TRAE* 294 (75.8) 202 (52.1) 317 (84.8) Any grade 3/4 AE 196 (50.5) 144 (37.1) 196 (52.4) Any grade 3/4 TRAE 100 (25.8) 50 (12.9) 138 (36.9) Any serious TRAE 68 (17.5)
Slide 24: Treatment-related hepatic or haemorrhage SMQ events
Treatment-related hepatic or haemorrhage SMQ events Event, n (%) T300+D (n=388) Durvalumab (n=388) Sorafenib (n=374) All grades Grade ≥3 All grades Grade ≥3 All grades Grade ≥3 Patients with hepatic SMQ TRAE 66 (17.0) 27 (7.0) 55 (14.2) 20 (5.2) 46 (12.3) 18 (4.8) Patients with hemorrhage SMQ TRAE 7
Slide 25: Conclusions
Conclusions • The HIMALAYA study was a large, Phase 3 study that included a global, heterogeneous population, representative of patients with uHCC • A single priming dose of tremelimumab plus regular interval durvalumab with the STRIDE (T300+D) regimen statistically significantly improved overall su
Slide 26: Commercial opportunity
3 Commercial opportunity Dave Fredrickson Executive Vice President, Oncology Business Unit
Slide 27: TOPAZ-1 potential first IO therapy in first-line advanced biliary tract cancer
TOPAZ-1 has the potential to become the first-ever IO therapy available for first-line, advanced biliary tract cancer patients Lack of innovation in biliary tract cancer TOPAZ-1 has practice-changing potential 10+ years • Trial stopped early at an interim analysis due to without innovation on top of
Slide 28: HIMALAYA innovative IO regimen in unresectable hepatocellular carcinoma
HIMALAYA – an innovative IO regimen delivering survival benefit to patients with advanced, unresectable hepatocellular carcinoma Large unmet need Innovative STRIDE regimen Clear efficacy, safety and in liver cancer with tremelimumab simplicity for patients 3rd • First IO+IO combination in first- lin
Slide 29: What's next in GI?
4 What’s next in GI? Susan Galbraith Executive Vice President, Oncology R&D
Slide 30: GI tumours are the next pillar for AstraZeneca in oncology
GI tumours are the next pillar for AstraZeneca in oncology complementing strong presence in lung & breast Annual worldwide incidence by cancer type Existing AstraZeneca presence 7000 Annual WW Incidence (000s) 6000 pancreas 5000 oesophagus 4000 hepatobiliary 3000 gastric 2000 1000 colorectal 0 Femal
Slide 31: AZ poised to become a leader in GI cancers
AZ poised to become a leader in GI cancers Late-stage clinical programmes Selected early-stage EMERALD-1: locoregional HCC; data H2 2022 datopotamab deruxtecan (TROP2 ADC) EMERALD-2: adjuvant HCC; data 2022 + HER2-ve gastric/GEJ and oesophageal MATTERHORN: resectable gastric / GEJ; data 2022+ KUNLUN
Slide 32: Closing and Q&A
5 Closing and Q&A
Slide 33: Investor Relations
Chris Sheldon Josie Afolabi chris.sheldon@astrazeneca.com josie.afolabi@astrazeneca.com Tom Waldron Morgan Sanford Investor tom.waldron@astrazeneca.com morgan.sanford@astrazeneca.com Relations Christer Gruvris Philip Sparks christer.gruvris@astrazeneca.com philip.sparks1@astrazeneca.com Lauren Swale
Slide 34: Appendix
A Appendix
Slide 35: TOPAZ-1
TOPAZ-1 35
Slide 36: Overall survival subgroup analysis
Overall survival Subgroup analysis Hazard ratio Subgroups (95% CI) All patients 0.80 (0.66–0.97) Age <65 0.80 (0.61–1.04) ≥65 0.79 (0.60–1.04) Sex Female 0.82 (0.62–1.08) Male 0.78 (0.60–1.01) Race Asian 0.73 (0.57–0.94) Non-Asian 0.89 (0.66–1.19) Region Asia 0.72 (0.56–0.94) Rest of the world 0.89
Slide 37: Overall survival in subgroups by PD-L1 expression
Overall survival in subgroups by PD-L1 expression Tumor Area Positivity (TAP) score using the Ventana PD-L1 (SP263) Assay Hazard ratio Subgroups (95% CI) All patients 0.80 (0.64–0.97) PD-L1 expression TAP ≥1% 0.79 (0.61–1.00) PD-L1 expression TAP <1% 0.86 (0.60–1.23) PD-L1 expression TAP ≥5% 0.70 (0
Slide 38: Grade 3/4 adverse events
Grade 3/4 adverse events Durvalumab Placebo Event, n (%) + GemCis (n=338) + GemCis (n=342) Any grade 3/4 AE (≥5%) Anemia 80 (23.7) 77 (22.5) Neutrophil count decreased 71 (21.0) 88 (25.7) Neutropenia 68 (20.1) 72 (21.1) Platelet count decreased 33 (9.8) 29 (8.5) Cholangitis 22 (6.5) 11 (3.2) Thrombo
Slide 39: HIMALAYA
HIMALAYA 39
Slide 40: Forest plot of overall survival
Forest plot of overall survival T300+D versus sorafenib in patient subgroups T300+D vs sorafenib HR (95% CI) All patients 0.78 (0.66–0.92) Sex Male 0.73 (0.61–0.88) Female 1.02 (0.67–1.56) Age <65 yr 0.82 (0.65–1.04) ≥65 yr 0.73 (0.58–0.93) Region Asia (except Japan) 0.71 (0.54–0.92) Rest of world (
Slide 41: Immune-mediated adverse events
Immune-mediated adverse events Event, n (%) T300+D (n=388) Durvalumab (n=388) Received Received Leading to Leading to All grades Grade 3 or 4 high-dose All grades Grade 3 or 4 high-dose discontinuation discontinuation steroids steroids Patients with immune- 139 (35.8) 49 (12.6) 78 (20.1) 22 (5.7) 64
Slide 42: Use of AstraZeneca slides from conference calls and webcasts
Use of AstraZeneca slides from conference calls and webcasts The AstraZeneca webcast, conference call and presentation slides (together the ‘AstraZeneca materials’) are for your personal, non-commercial use only. You may not copy, reproduce, republish, post, broadcast, transmit, make available to th
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