ESMO-2021-presentation-newsom-davis-watch-the-ESMO-meet-the-investigator-session.pdf

poster

1. Connecting with the
experts: your questions on
IMpower010 answered
Sunday 19 September 2021
17.00–17.30 CEST
This scientific meeting is sponsored by F. Hoffmann-La Roche Ltd
This is a non-promotional meeting intended to facilitate transparent scientific exchange regarding developments in medical research and disease
management. It is intended for healthcare professionals outside the United States of America (US). The content of this symposiummay include
scientific information about experimental or investigational compounds, indications and services that are not approved or valid in your jurisdiction
M-XX-00006724

2. Connecting with the experts: your questions on
IMpower010 answered
Opening and introduction
Tom Newsom-Davis
Q&A
IMpower010: in-depth perspective on
immunotherapy in early-stage NSCLC
Heather Wakelee
Jay M. Lee
Tom Newsom-Davis, MBBS FRCP PhD (Chair)
Chelsea and Westminster Hospital, UK
Medical oncologist
Heather Wakelee, MD
Stanford University, USA
Medical oncologist
Jay M. Lee, MD
University of California, Los Angeles, USA
Thoracic surgeon
Please note that this meeting will be recorded

3. Disclosures
Heather Wakelee
Consulting or advisory role: AstraZeneca, Blueprint Medicines, Daiichi Sankyo, Helsinn Therapeutics, Janssen Oncology, Mirati
Therapeutics, and Xcovery
Research funding to institution: ACEA Biosciences, Arrys Therapeutics, AstraZeneca/MedImmune, Bristol-Myers Squibb, Celgene,
Clovis Oncology, Exelixis, Roche/Genentech, Gilead Sciences, Merck, Novartis, Pharmacyclics, Seattle Genetics, and Xcovery
Uncompensated relationships: Genentech/Roche, Merck, and Takeda
Thomas Newsom-Davis
Honoraria: Amgen, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Lilly, MSD, Novartis, Otsuka, Pfizer, Roche/Genentech,
and Takeda
Consulting or advisory role: Amgen, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Lilly, MSD, Novartis, Otsuka, Pfizer,
Roche/Genentech, and Takeda
Speakers' bureau: AstraZeneca, MSD, Roche/Genentech, and Takeda
Jay M. Lee
Stock and other ownership interests: Moderna Therapeutics
Consulting or advisory role: AstraZeneca, Bristol Myers Squibb Foundation, Roche/Genentech, and Novartis
Research funding: Merck
Travel, accommodations, expenses: Roche/Genentech
Uncompensated relationships: Roche/Genentech, and Novartis

4. IMpower010: in-depth perspective on immunotherapy
in early-stage NSCLC

5. Adjuvant platinum-based chemotherapy changed the
standard of care for resected NSCLC over 15 years ago
DFS, disease-free survival; OS, overall survival
Pignon, et al. J Clin Oncol 2008
Adjuvant chemotherapy versus no chemotherapy (LACE meta-analysis)
OS HR=0.89
improvement in 5-year OS
across all patients~5%
DFS HR=0.84
improvement in 5-year DFS
across all patients~6%
Figures not included due to copyright restrictions –please see original publication, referenced below

6. Two phase III studies have shown a DFS benefit in
early-stage NSCLC in biomarker-defined populations
EGFR, epidermal growth factor receptor; PD-L1, programmed death-ligand 1; TC, tumour cell
*Per AJCC 7
th
edition
▼This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions.
Adverse events should be reported to your local Regulatory Authority and in copy to the local Roche office
1. Wu, et al. N Engl J Med 2020; 2. Wakelee, et al. ASCO 2021 (Abs 8500)
Significant DFS benefit in
EGFR+
stage IB–IIIA NSCLC*
Significant DFS benefit in
PD-L1 TC ≥1%
stage II–IIIA NSCLC*
ADAURA
1
Adjuvant osimertinib after surgery
and optional chemotherapy
IMpower010
2
Adjuvant atezolizumab▼after
surgery and chemotherapy
Adjuvant osimertinib is FDA-and EMA-
approved in EGFR+ early-stage NSCLC
Presented at the
2021 ASCO Annual Meeting

7. IMpower010: global, phase III study of adjuvant atezolizumab
after surgery and chemotherapy in early-stage NSCLC
BSC, best supportive care; IC, tumour-infiltrating immune cells; ITT, intention-to-treat
Both arms included observation and regular scans for disease recurrence on the same schedule
*Per SP142 assay
Wakelee, et al. ASCO 2021 (Abs 8500)
Stratification factors
•Male vs female
•Stage (IB vs II vs IIIA)
•Histology
•PD-L1 tumour expression status*:
TC2/3 and any IC vs TC0/1 and
IC2/3 vs TC0/1 and IC0/1
Primary endpoints
•Investigator-assessed DFS tested hierarchically:
1.PD-L1 TC ≥1% (SP263) stage II–IIIA population
2.All-randomised stage II–IIIA population
3.ITT (all-randomised stage IB–IIIA) population
R
1:1
No crossover
Atezolizumab
1200 mg q21d
16 cycles
BSC
N=1005
Survival follow
-
up
Completely resected
stage IB–IIIA NSCLC
per UICC/AJCC v7
•Stage IB tumours ≥4 cm
•ECOG PS 0–1
•Lobectomy/pneumonectomy
•Tumour tissue for PD-L1 analysis
1–4 cycles
cisplatin +
pemetrexed,
gemcitabine,
docetaxel or
vinorelbine
N=1280

8. Why was a hierarchical testing approach used
in IMpower010?
*Two-sided α=0.05
Wakelee, et al. ASCO 2021 (Abs 8500)
DFS in PD-L1 TC ≥1%
stage II–IIIA population*
DFS in all-randomised
stage II–IIIA population*
DFS in ITT population*
(all-randomised stage IB–IIIA)
OS in ITT population*
(all-randomised stage IB–IIIA)
If positive:
If positive:
If positive:
Analysis populations defined by PD-L1 expression and
disease stage were considered due to the predictive
and prognostic value of these factors

9. DFS is an established surrogate endpoint, which can
help bring effective treatments into the clinic rapidly
1
PFS, progression-free survival; RFS, recurrence-free survival
1. Hellmann, et al. Lancet Oncol 2014; 2. Arriagada, et al. N Engl J Med 2004; 3. Dunant, et al. Clin Cancer Res 2005; 4. Winton, et al. N Engl J Med 2005; 5. Douillard, et al Lancet Oncol 2006
6. Felip, et al. J Clin Oncol 2010; 7. Gilligan, et al. Lancet 2007; 8. Pisters, et al. J Clin Oncol 2010; 9. Strauss, et al.J Clin Oncol 2008; 10. Mauguen, et al. Lancet Oncol 2013
A meta-analysis found DFS to be a valid surrogate endpoint for OS with adjuvant
chemotherapy and radiotherapy in resectable early-stage NSCLC
10
OS is the gold standard, but evaluating OS takes a long time in early-stage cancers
1
Trial
DFS/RFS/
PFS HR OS HR
Time from first
patient recruited until
publication of OS
% received all planned
chemotherapy cycles
IALT
2
(adjuvant) 0.83 (DFS) 0.86 9 years 76%
3
JBR.10
4
(adjuvant) 0.60 (RFS) 0.69 11 years 45%
ANITA
5
(adjuvant) 0.76 (DFS) 0.80 12 years 50%
NATCH
6
(adjuvant
vs neoadjuvant)
Adjuvant: 0.96 (DFS)
Neoadjuvant: 0.92 (DFS)
Adjuvant: 1.01
Neoadjuvant: 0.88
10 years
Adjuvant: 61%
Neoadjuvant: 90%
LU22
7
(neoadjuvant) 0.96 (PFS) 1.02 10 years 75%
SWOG9900
8
(neoadjuvant) 0.80 (PFS) 0.79 11 years 79%
CALGB 9633
9
(neoadjuvant) 0.80 (DFS) 0.83 12 years 86%

10. Baseline characteristics in the ITT population were
well balanced
Clinical cut-off: 21 January 2021
Wakelee, et al. ASCO 2021 (Abs 8500)
Characteristic Atezolizumab (n=507) BSC (n=498)
Median (range) age, years 62 (33–83) 62 (26–84)
Age ≥65 years, % 36 40
Male, % 66 67
Race, %
White 71 76
Asian 26 22
Other 3 2
ECOG PS 0 / 1, % 54 / 46 57 / 43
Non-squamous histology, % 65 66
Stage, %
IB 13 12
IIA 29 30
IIB 18 17
IIIA 40 42
Never / current or previous smoker, % 22 / 78 22 / 78
PD-L1 TC ≥1% by SP263, %* 57 52
*97% of patients in the ITT population had PD-L1 status assessed by SP263

11. 34% reduction in risk of disease recurrence or death in
the PD-L1 TC ≥1%* stage II–IIIA population
Clinical cut-off: 21 January 2021
*PD-L1 expression determined using the SP263 assay;
‡
Stratified log-rank;
§
Crossed the significance boundary for DFS
Wakelee, et al. ASCO 2021 (Abs 8500)
248
228
Atezolizumab
BSC
No. at risk
235
212
225
186
217
169
206
160
198
151
190
142
181
135
159
117
134
97
111
80
76
59
54
38
31
21
22
14
12
7
8
6
3
4
3
3
DFS HR=0.66 (95% CI: 0.50, 0.88)
p=0.004
‡§
Median follow-up 32.8 months
Median 35.3 months
Median not estimable
2-year DFS estimates
75%vs 61%
3-year DFS estimates
60%vs 48%
Atezolizumab
BSC
DFS estimate
Time (months)
1.0
0.8
0.6
0.4
0.2
0
03691215182124273033363942 48 545145 57

12. Stratified HR=0.66 (95% CI: 0.50,0.88)
p=0.004
‡
Stratified HR=0.79 (95% CI: 0.64, 0.96)
p=0.02
‡
Stratified HR=0.81 (95% CI: 0.67, 0.99)
p=0.04
‡
Study continues to final DFS
analysis for the ITT population
DFS in the primary populations
*Two-sided α=0.05;
‡
Stratified log-rank
Wakelee, et al. ASCO 2021 (Abs 8500)
DFS in PD-L1 TC ≥1%
stage II–IIIA population*
DFS in all-randomised
stage II–IIIA population*
DFS in ITT population*
(all-randomised stage IB–IIIA)
OS in ITT population*
(all-randomised stage IB–IIIA)
If positive:
If positive:
If positive:
Endpoint was met at DFS IA
Significance boundary not crossed at DFS IA in the ITT population, and testing will continue to the final DFS analysis
OS data were immature, and endpoint has not yet been formally tested
The secondary endpoint of OS will be formally tested
when DFS is positive in all three primary populations
and the prespecified number of events is reached

13. A DFS benefit was maintained across key clinical
subgroups in the PD-L1 TC ≥1% stage II–IIIA population
ALK, anaplastic lymphoma kinase
Clinical cut-off: 21 January 2021; PD-L1 expression determined using the SP263 assay
*Stratified for all patients, unstratified for all other subgroups;
‡
89.2% and 80.7% of patients in the ITT population with unknown
EGFRor ALK status, respectively, had squamous NSCLC and were not required to undergo local or central testing
Wakelee, et al. ASCO 2021 (Abs 8500)

14. Enriched clinical benefit was observed in patients
whose tumours express PD-L1*
Clinical cut-off: 21 January 2021
*Per SP263 assay;
‡
Stratified for all patients and PD-L1 TC ≥1%; unstratified for all other subgroups;
§
DFS analyses in the PD-L1 TC <1%
and TC 1–49% subgroups were exploratory;
¶
23 patients had unknown PD-L1 status as assessed by SP263
Felip, et al. ESMO 2021 (Abs LBA9)
All-randomised stage II–IIIA populationn HR (95% CI)
‡§
PD-L1 status by SP263
TC ≥1% 476 0.66 (0.50, 0.88)
TC ≥50% 229 0.43 (0.27, 0.68)
TC 1–49% 247 0.87 (0.60, 1.26)
TC <1% 383 0.97 (0.72, 1.31)
All patients
¶ 882 0.79 (0.64, 0.96)
0.1 1.0 10.0
HR
BSC betterAtezolizumab better
Presidential symposium 3
Monday 20 September
16.15–16.25 CEST
Additional data will be presented

15. Phase III studies are underway to investigate targeted therapies
for other driver alterations (e.g. ALK) in early-stage NSCLC
What should be the choice of treatment for patients
with EGFR+, early-stage NSCLC?
*Per SP263 assay;
‡
Unstratified HR;
§
89.2% and 80.7% of patients in the ITT population with unknown
EGFRor ALKstatus, respectively, had squamous NSCLC and were not required to undergo local or central testing
1. Wakelee, et al. ASCO 2021 (Abs 8500); 2. Wu, et al. N Engl J Med 2020
Significant DFS benefit in EGFR+
Stage IB–IIIA NSCLC
HR=0.20 (99.12% CI: 0.14, 0.30)
Stage II–IIIA NSCLC
HR=0.17 (99.06% CI: 0.11, 0.26)
ADAURA
2
Adjuvant osimertinib after surgery
and optional chemotherapy
IMpower010
1
Adjuvant atezolizumab after
surgery and chemotherapy
EGFRmutation status n HR (95% CI)
‡
PD-L1 TC ≥1%*, stage II–IIIA population
Yes 43 0.57 (0.26, 1.24)
No 248 0.67 (0.45, 1.00)
Unknown
§ 185 0.61 (0.38, 0.98)
All-randomised, stage II–IIIA population
Yes 109 0.99 (0.60, 1.62)
No 463 0.79 (0.59, 1.05)
Unknown
§ 310 0.70 (0.49, 1.01)
0.1 1.0 10.0
HR
BSC betterAtezolizumab better
Adjuvant osimertinib is FDA-and EMA-approved
in EGFR+ early-stage NSCLC

16. OS data are not yet mature, but a trend was observed
in the PD-L1 TC ≥1% stage II−IIIA population
Clinical cut-off: 21 January 2021
*Stratified
Wakelee, et al. ASCO 2021 (Abs 8500)
Atezolizumab
BSC
OS estimate
Time (months)
1.0
0.8
0.6
0.4
0.2
0
03691215182124273033363942 48 545145 6057
All-randomised stage II–IIIAOS HR*=0.99 (95% CI: 0.73, 1.33)
ITTOS HR*=1.07 (95% CI: 0.80, 1.42)
OS HR*=0.77(95% CI: 0.51, 1.17)
Median not estimable
Median not estimable
248
228
Atezolizumab
BSC
No. at risk
241
220
241
214
237
210
234
205
231
201
225
198
222
192
218
185
196
172
164
135
126
110
99
80
62
57
40
32
26
17
13
10
5
7
3
5
NE
2

17. The safety profile of atezolizumab was manageable and
consistent with prior experience of atezolizumab monotherapy
Clinical cut-off: 21 January 2021; data are from the safety population (all randomisedpatients who received ≥1 atezolizumab dose or for BSC, had ≥1 post-baseline assessment)
*Interstitial lung disease
§
; pneumothorax; multiple organ dysfunction syndrome
§
; cerebrovascular accident; arrhythmia; myocarditis
§
; acute myeloid leukemia
§
; acute cardiac failure
‡
Pneumonia; pulmonary embolism; cardiac tamponade and septic shock in the same patient;
§
Treatment related per investigator
Wakelee, et al. ASCO 2021 (Abs 8500)
Category
Atezolizumab
(n=495)
BSC
(n=495)
Any-cause AE, % 93 71
Treatment-related AE, % 68 –
Grade 3–4 AE, % 22 12
Treatment-related grade 3–4 AE, % 11 –
Serious AE, % 18 8
Treatment-related serious AE, % 7 –
Grade 5 AE, % 2* 1
‡
Treatment-related grade 5 AE, % 1 –

18. Integrated approaches to patient care will be required
to navigate the treatment landscape
Multidisciplinary teams
and referral to oncology
Biomarker testing
Early communication with
patients about adjuvant
systemic therapy
EGFR
PD-L1
ALK?

19. Q&A

20. Don’t forget!
Presidential symposium 3
Monday 20 September
16.15–16.25 CEST
Additional IMpower010 data on
PD-L1 subgroups and patterns of
progression will be presented
Please complete the short evaluation pollat the end of the meeting
Thank you for attending this meeting!