esmo congress 2021

Supported by Eli Lilly and Company.

Eli Lilly and Company has not influenced the content of this publication

Developed in association with the

European Thoracic Oncology Platform

ESMO Congress 2021

16–21 September 2021

Letter from Prof Rolf Stahel

Dear Colleagues

It is my pleasure to present this ETOP slide set which has been designed to highlight and summarise key findings in thoracic

cancers from the major congresses in 2021. This slide set specifically focuses on the ESMO Congress 2021 and is available

in 4 languages – English, French, Chinese and Japanese.

The area of clinical research in oncology is a challenging and ever changing environment. Within this environment we all value

access to scientific data and research which helps to educate and inspire further advancements in our roles as scientists,

clinicians and educators. I hope you find this review of the latest developments in thoracic cancers of benefit to you in your

practice. If you would like to share your thoughts with us we would welcome your comments. Please send any correspondence

to [email protected].

I would like to thank our ETOP members Drs Enriqueta Felip, Solange Peters, Martin Reck and Egbert Smit for their roles as

Editors – for prioritising abstracts and reviewing slide content. The slide set you see before you would not be possible without

their commitment and hard work.

Finally, we are also very grateful to Lilly Oncology for their financial, administrative and logistical support in the realisation of

this complex yet rewarding activity.

Yours sincerely,

Rolf Stahel

President, ETOP Foundation Council

mailto:[email protected]

ETOP Medical Oncology Slide Deck Editors 2021

Focus: biomarkers (all stages)

Dr Enriqueta Felip

Oncology Department, Vall d'Hebron University Hospital, Barcelona, Spain

Focus: advanced NSCLC (not radically treatable stage III & stage IV)

Dr Solange Peters

Multidisciplinary Oncology Center, Lausanne Cancer Center, Lausanne, Switzerland

Focus: other malignancies, SCLC, mesothelioma, rare tumors

Dr Martin Reck

Department of Thoracic Oncology, Hospital Grosshansdorf, Grosshansdorf, Germany

Focus: early and locally advanced NSCLC (stages I–III)

Dr Egbert Smit

Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, Netherlands

4

Contents

• Screening, biomarkers and prevention

• Early stage and locally advanced NSCLC – Stages I, II and III

• Advanced NSCLC – Not radically treatable stage III and stage IV

– First line

– Later lines

• Other malignancies

– SCLC, mesothelioma and thymic epithelial tumors

Screening, biomarkers and prevention

6

LBA68: Clinical value of pre-treatment T-Cell receptors (TCR) repertoire in non-small cell lung cancer (NSCLC) patients treated with single agent immunotherapy – Abed A, et al

• Study objective

– To evaluate whether pre-treatment T-cell receptor repertoire metricsa can predict response to pembrolizumab

in patients with NSCLC

• Methods

– DNA samples were prospectively collected from 50 patients prior to treatment and TCR sequencing was

performed

– TCR repertoire variables were correlated with ORR, PFS, OS and immune-related toxicity

Abed A, et al. Ann Oncol 2021;32(suppl):Abstr LBA68aAssessed using Omcomine™ TCR-beta assay

7


• Key results

Abed A, et al. Ann Oncol 2021;32(suppl):Abstr LBA68

Numbers of

unique clones

TCR Shannon

diversity

TCR evenness

No. of unique clonesN

o. o

f u

niq

ue

clo

ne

s

NR R

p=0.038

10000

8000

6000

4000

2000

0

NR R

Shannon diversity

p=0.021

1.1

1.0

0.9

0.8

0.7Sh

an

no

n d

ive

rsity

ORR

TCR clonality

PFS

PF

S

100

75

50

25

0

10008006004002000

Time, days

HR 0.40(95%CI 0.14, 1.17);

p=0.031

No. of unique clones

n=11

n=18

100

75

50

25

0

10008006004002000

Time, days

HR 0.4495%CI 0.16, 1.21)

p=0.041

Shannon diversity

n=19

n=10

100

75

50

25

0

10008006004002000

Time, days

HR 0.3195%CI 0.11, 0.94);

p=0.033

Evenness

n=6

n=23

Clonality100

75

50

25

0

10008006004002000

Time, days

HR 3.1895%CI 1.06, 9.53);

p=0.033

n=6

n=23PF

S

Low

High

8


• Key results (cont.)


TCR Shannon

diversity

TCR evenness

No. of unique

clones

TCR

convergence

TCR clonality

Shannon diversity

Pts

with

to

xic

ity, %

15

10

25

0

HighLow

RR 1.67 (0.84–3.16)

p=0.135

Evenness

Pts

with

to

xic

ity, %

15

10

25

0

HighLow

RR 2.30 (1.27–2.45)

p=0.017

Toxicity

Nil toxicity

Clonality

Pts

with

to

xic

ity, %

15

10

25

0

HighLow

RR 2.30 (1.27–3.90)

p=0.017

No. of unique clones

Pts

with

to

xic

ity, %

HighLow

RR 0.92 (0.48–1.67)

p=0.55610

8

6

4

2

0

Convergence

Pts

with

to

xic

ity, %

HighLow

RR 0.73 (0.36–1.41)

p=0.28210

8

6

4

2

0

9



– TRVB6-4, 10-2 and 10-3 gene usage appears to be more frequent among non-responders

• Conclusions

– In patients with NSCLC receiving pembrolizumab, low TCR diversity at baseline was associated with

significant improvements in ORR and PFS, but not OS

– Low TCR evenness and increased clonality were significantly associated with increased immune-related

toxicity


Early stage and locally advanced NSCLC –Stages I, II and III

11

LBA9: IMpower010: sites of relapse and subsequent therapy from a phase 3 study of atezolizumab vs best supportive care after adjuvant chemotherapy in stage IB-IIIA NSCLC – Felip E, et al

• Study objective

– To evaluate the efficacy and safety of adjuvant atezolizumab in patients with advanced NSCLC in the

IMpower010 study

Felip E, et al. Ann Oncol 2021;32(suppl):Abstr LBA9

R

1:1

Stratification

• Sex

• Stage (IB vs. II vs. IIIA)

• Histology

• PD-L1 statusa

Key patient inclusion criteria

• Stage IB (≥4 cm)–IIIA NSCLC

• Completely resected

• ECOG PS 0−1

(n=1280)

Best supportive care

(n=495)

Atezolizumab 1200 mg q3w

(16 cycles)

(n=495)

Cisplatin +

pemetrexed, docetaxel,

gemcitabine or vinorelbine

(1–4 cycles)

aTC2/3 and any IC vs. TC0/1 and IC2/3 vs. TC0/1 and IC0/1

Primary endpoint

• DFS

Secondary endpoints

• OS, safety

12


• Key results


DFS by PD-L1 status

All-randomised stage II-IIIA population

Subgroup (including EGFR/ALK+) n HR (95%Cl)

PD-L1 status by SP263

TC <1% 383 0.97 (0.72, 1.31)

TC ≥1% 476 0.66 (0.50, 0.88)

TC 1–49% 247 0.87 (0.60, 1.26)

TC ≥50% 229 0.43 (0.27, 0.68)

All patients 882 0.79 (0.64, 0.96)

Subgroup (excluding EGFR/ALK+) n HR (95%Cl)

PD-L1 status by SP263

TC <1% 312 0.92 (0.65, 1.30)

TC ≥1% 410 0.62 (0.45, 0.86)

TC 1–49% 201 0.82 (0.54, 1.25)

TC ≥50% 209 0.43 (0.26, 0.71)

All patients 743 0.74 (0.59, 0.93)

0.1 1.0 10.0

HRAtezolizumab better BSC better

0.1 1.0 10.0

HRAtezolizumab better BSC better

13




80 PD-L1 TC ≥1% stage II–IIIA All randomized stage II–IIIA70

60

50

40

30

20

10

0Atezolizumab

(n=73)

BSC

(n=102)

Atezolizumab

(n=147)

BSC

(n=189)

Atezolizumab

(n=156)

BSC

(n=203)

Pa

tie

nts

, %

ITT stage IB–IIIA69.9

66.7 67.3 66.1 65.4 64.5

54.8

46.1 47.6 46.0 46.2 45.3

11.0

35.3

12.9

32.3

12.2

32.0

13.7

19.7

14.818.6

14.3

9.65.9

11.68.5

10.98.4

16.4

Any treatment Chemotherapy CIT Targeted TKI Targeted mAb

Post-relapse systemic non-protocol anticancer therapy

Other post-relapse

treatments, n (%)

PD-L1 TC ≥1% stage II–IIIA All randomized stage II–IIIA ITT stage IB–IIIA

Atezolizumab (n=73) BSC (n=102) Atezolizumab (n=147) BSC (n=189) Atezolizumab (n=156) BSC (n=203)

Radiotherapy 32 (43.8) 48 (47.1) 54 (36.7) 72 (38.1) 54 (34.6) 76 (37.4)

Surgery 12 (16.4) 11 (10.8) 23 (15.6) 26 (13.8) 23 (14.7) 32 (15.8)

14




30

25

20

15

10

5

0

Media

n tim

e t

o r

ela

pse,

mo

Range, mo

16.8 17.3

24.0

18.2

12.213.5

8.6

13.512.1 12.5

8.6

13.512.0

10.4

5.3

12.010.6 10.4

8.2

12.0 12.010.6

8.2

12.0

LR

only

Distant

only

LR and

distant

CNS

only

LR

only

Distant

only

LR and

distant

CNS

only

LR

only

Distant

only

LR and

distant

CNS

only

Median (range) time to any relapse: 17.6 mo (0.7–42.3)






Atezo:

BSC:

PD-L1 TC≥1% stage II–IIIA All randomized stage II–IIIA ITT stage IB–IIIA

n=35 n=42 n=28 n=40 n=9 n=17 n=8 n=12 n=58 n=72 n=62 n=77 n=25 n=34 n=14 n=23 n=59 n=75 n=67 n=82 n=27 n=38 n=14 n=25

Time from randomization to relapse

Atezolizumab BSC

15



• Conclusions

– In patients with advanced NSCLC, atezolizumab showed similar patterns of relapse compared with best

supportive care, at a slower rate in PD-L1 TC≥1 patients

– In an exploratory analysis, patients with PD-L1 TC 1–49% showed DFS benefit


Site of relapse, n (%)

Atezolizumab

(n=156)

BSC

(n=203)

Locoregional only 59 (37.8) 75 (36.9)

Distant only 67 (42.9) 82 (40.4)

CNS 16 (10.3) 29 (14.3)

Bone/bone marrow 14 (9.0) 14 (6.9)

Contralateral lung 10 (6.4) 16 (7.9)

Liver 10 (6.4) 8 (3.9)

Lymph node 8 (5.1) 11 (5.4)

Ipsilateral lung 6 (3.8) 8 (3.9)

Subcutaneous tissue 1 (0.6) 2 (1.0)

Other 16 (10.3) 15 (7.4)

Site of relapse, n (%)

Atezolizumab

(n=156)

BSC

(n=203)

Locoregional and distant 27 (17.3) 38 (18.7)

Bone/bone marrow 11 (7.1) 8 (3.9)

Contralateral lung 7 (4.5) 10 (4.9)

Liver 6 (3.8) 4 (2.0)

Lymph node 5 (3.2) 9 (4.4)

Ipsilateral lung 5 (3.2) 1 (0.5)

CNS 3 (1.9) 6 (3.0)

Subcutaneous tissue 1 (0.6) 0

Other 6 (3.8) 13 (6.4)

16

1170O: An international randomized trial, comparing post-operative conformal radiotherapy (PORT) to no PORT, in patients with completely resected non-small cell lung cancer (NSCLC) and mediastinal N2 involvement: characterisation of PORT efficacy in Lung ART (IFCT-0503, UK NCRI, SAKK) – Le Pechoux C, et al

• Study objective

– To investigate the survival benefit of post-operative radiotherapy in patients with mediastinal lymph node-

positive NSCLC in the Lung ART study

Le Pechoux C, et al. Ann Oncol 2021;32(suppl):Abstr 1170O

Primary endpoint

• DFS

Secondary endpoints

• OS, patterns of relapse, local failure, second

cancers, safety

R

1:1

Stratification

• Centre

• Administration of CT (none vs. post-op CT vs. pre-op CT)

• Histology (SCC vs. other)

• Extent of mediastinal lymph node involvement (0 vs. 1 vs. 2+)

• Use of pre-treatment PET scan (yes vs. no)


• Completely resected stage

III NSCLC

• Confirmed N2 nodal

involvement

• Pre- and /or post-operative

chemotherapy

• PS 0–2

(n=501)

Control

(n=249)

Conformal PORT (54 Gy/5.5 weeks)

(n=252)

17


• Key results


PORT arm Control arm

Pro

ba

bili

ty, %

100

80

60

40

20

0

DFS

Death

Survival time, months

10896847260483624120

DM

MR

Pro

ba

bili

ty, %

100

80

60

40

20

0

Survival time, months

60483624120 108968472

DFS

Death

DM

MR

Event, n (%) PORT (n=144) Control (n=152) Total (n=296) HR (95%CI)a

Mediastinal relapse (MR) 36 (25) 70 (46) 106 (36) 0.45 (0.30, 0.69)

All distant metastases (DM) 87 (60) 74 (49) 161 (54) 1.17 (0.86, 1.60)

Including brain metastases (BM) 34 (24) 27 (18) 61 (21) 1.33 (0.78, 2.26)

Death 21 (15) 8 (5) 29 (10) 2.63 (1.18, 5.84)

aFine-Gray sub-distribution hazard model

18



• Conclusions

– In patients with completely resected NSCLC and mediastinal N2 involvement, use of post-operative

radiotherapy reduced the risk of mediastinal recurrence, but had no significant impact on survival rate

– Prognostic factors associated with different DFS included quality of resection, extent of mediastinal

involvement and lymph node ratio


Prognostic factors for DFS HR p-value

Treatment arm radiotherapy (vs. control) 0.89 0.33

Gender female (vs. male) 0.73 0.02

Histology squamous cell carcinoma (vs. other) 0.71 0.03

N2 involvement with N1 involvement (left or right) (vs. without) 1.50 <0.01

Number of mediastinal nodes stations involved (vs. 1) 0.01

None 0.99

≥2 1.46

Quality of resection (vs. R0) <0.001

R (uncertain) 1.29

R1 (extra-capsular extension) 1.31

R2a 1.95

bTwo patients should not have been included

19

1151MO: Pathological response is an independent factor of overall survival and disease-free survival after neoadjuvant durvalumab in resectable non-small cell lung cancer (NSCLC) in the IFCT-1601 IONESCO phase 2 trial – Wislez M, et al

• Study objective

– To assess the feasibility of preoperative neoadjuvant durvalumab in patients with early stage, resectable

NSCLC in the IFCT-1601 IONESCO study

Wislez M, et al. Ann Oncol 2021;32(suppl):Abstr 1151MO

Primary endpoint

• Complete surgical resection (R0)

Secondary endpoints

• Mortality (90 days post-operative), OS,

DFS, RR, safety


• Stage IB (≥4 cm)–IIIA (no N2)

NSCLC

• Baselines tissue specimen

available

• ECOG PS 0–1

(n=50)

Durvalumab 750 mg

D1, 15, 29

(n=46)

Surgery 2–14 days

after last infusion

(n=43)

Follow-up at

4 weeks,

6 months, or

1 year after surgery

20


• Key results


Residual viable tumour cellsa (RVT %) is associated with OS and DFS

Cox model for OS

Hazard ratio and 95%CI

Cox model for DFS

Hazard ratio and 95%CI

Male (vs. female)

Stage IIA (vs. IB)

Stage IIB (vs. IB)

RVT (for increasing value)

Squamous cell carcinoma

(vs. adenocarcinoma)

PS 1 (vs. 0)

Age (for increasing value)

Pneumonectomy (vs. lobectomy)

PD-L1 ≥1% (vs. <1%)

0.01 0.1 1 10 100

Favours longer OS

HR LCL UCL

0.73

1.24

0.81

1.64

2.30

0.76

1.11

1.50

0.67

0.17

0.13

0.09

1.03

0.55

0.09

0.99

0.29

0.12

3.08

11.94

7.24

2.60

9.62

6.23

1.24

7.77

3.69

LCL UCL

0.01 0.1 1 10 100

Favours longer DFS

HR

1.42

1.27

0.77

1.71

1.31

0.30

0.96

0.56

0.54

0.46

0.25

0.16

1.08

0.49

0.04

0.89

0.12

0.10

4.41

6.30

3.63

2.69

3.50

2.29

1.04

2.52

2.92

aAnalysed using Cox regression model including patient characteristics (age, gender, PS,

smoking status), histology, PD-L1 TPS, stage and surgical procedure. % RVT was used as a

continuous variable using each 10% increase as a unit

21



Conclusions

– In patients with resectable NSCLC, residual viable tumour cells was found to be an independent prognostic

factor for OS and DFS outcomes


n

Complete resection (R0), n (%) 46 41 (89.1)

BOR, n (%)

CR 46 0

PR 46 4 (8.7)

SD 46 36 (78.3)

PD 46 6 (13)

RVT, median (range)a 43 36.1 (0–73.3)

Complete pathological response, n, % 43 3 (7)

n=46

Major pathological response, n (%) 8 (18.6)

12-mo DFS, % (95%CI) 78.3 (63.4, 87.7)

12-mo OS, % (95%CI) 89.1 (75.8, 95.3)

18-mo DFS, % (95%CI) 73.7 (58.4, 84.1)

18-mo OS, % (95%CI) 89.1 (75.8, 95.3)

aDegree of pathologic response was measured using % of residual viable tumour cells

(RVT) in the primary tumour and in any involved lymph nodes

22

1172MO: Durvalumab consolidation in patients with stage III non-resecable NSCLC with driver genomic alterations – Riudavets Melia M, et al

• Study objective

– To assess the effectiveness of durvalumab in patients with stage III, unresectable NSCLC harbouring

oncogenic driver alterations

• Methods

– A multicentre, retrospective study performed on data collected from 323 patients between April 2015 and

October 2020 from 25 centres across Europe and US

– Oncogenic driver alterations included:

• EGFR, BRAF and KRAS mutations

• ALK and ROS1 rearrangements

Riudavets Melia M, et al. Ann Oncol 2021;32(suppl):Abstr 1172MO

23

PFS by driver of genomic alteration (dGA) status


Median follow-up: 18.5 mo (95%CI 16.9, 21.0)

mPFS: 17.5 mo (95%CI 13.2, 24.9)

mOS: 47.0 mo (95%CI 47.0, NR)


PF

S, %

100

80

60

40

20

0

252020151050

Time, months

16406191146202280

14811193243

Non-dGA: 18 mo (95%CI 13.4, 28.3)

dGA: 14.9 mo (95% CI 8.1, NR)

p=1.0

No. at risk

Non-dGA

dGA

• Key results

24




PFS by individual dGA

PF

S, %

100

80

60

40

20

0

No. at risk Time, months

302520151050

1122258

0379162326

0001259

EGFRm

KRASm

Other

KRASm: NR (95%CI 11.3, NR)

EGFRm: 9.0 mo (95%CI 5.8, NR)

Other driver: 7.8 mo (95%CI 3.9, NR)

p=0.02

mPFS, mo

(95%CI)

18-mo OS rate, %

(95%CI)

Overall dGA 14.9 (8.1, NR) 93.4 (84.7, 100)

KRASm (n=26)

KRASm G12C (n=8)

NR (14.9, NR)

NR (11.3, NR)

89.7 (76.8, 100)

87.5 (67.3, 100)

EGFRm (n=8)

EGFRm del19/ex21 (n=6)

9.0 (5.8, NR)

8.1 (5.8, NR)

100 (NR, NR)

100 (NR, NR)

BRAFm (n=5)

BRAFm V600E (n=4)

3.9 (3.9, NR)

8.4 (3.9, NR)

100 (NR, NR)

100 (NR, NR)

ALKr (n=4) 7.8 (7.7, NR) 100 (NR, NR)

25


• Conclusions

– In patients with unresectable stage III NSCLC, durvalumab consolidation treatment showed greater benefit in

PFS in the KRAS mutation subgroup compared with other genomic alternations

– Analysis on a larger cohort is mandatory and ongoing


Advanced NSCLCNot radically treatable stage III and stage IV

First line

27

LBA42: COAST: an open-label, randomised, phase 2 platform study of durvalumab alone or in combination with novel agents in patients with locally advanced, unresectable, stage III NSCLC – Martinez-Marti A, et al

• Study objective

– To evaluate the efficacy and safety of durvalumab in combination with either oleclumab or monalizumab in

patients with stage III NSCLC following concomitant chemotherapy in the COAST study

Martinez-Marti A, et al. Ann Oncol 2021;32(suppl):Abstr LBA42

Primary endpoint

• ORR (RECIST v1.1, investigator assessed)

Secondary endpoints

• DoR, DCR, PFS, OS, safety, pharmacokinetics

R

1:1:1

Stratification

• Histology (adenocarcinoma

vs. other)


• Unresectable, locally

advanced stage III NSCLC

• No PD after prior CRT

• ECOG PS 0–1

(n=189) Durvalumab 1500 mg q4w +

monalizumab 750 mg q2w

(n=62)

Durvalumab 1500 mg q4w

(n=67)

Durvalumab 1500 mg q4w +

oleclumab 3000 mga

(n=60)

aOleclumab q2w for cycle 1 or 2, then q4w starting cycle 3

28


• Key results


Antitumor activity by investigator assessment

Durvalumab

(n=67)

Durvalumab + oleclumab

(n=60)

Durvalumab + monalizumab

(n=62)

Confirmed ORR, n (%) [95%CI] 12 (17.9) [9.6, 29.2] 18 (30.0) [18.8, 43.2] 22 (35.5) [23.7, 48.7]

Confirmed + unconfirmed ORR, n (%) (95%CI) 17 (25.4) [15.5, 37.5] 23 (38.3) [26.1, 51.8] 23 (37.1) [25.2, 50.3]

ORR odds ratio (95%CI) - 1.83 (0.80, 4.20) 1.77 (0.77, 4.11)

Objective responses by RECIST, n (%)

CR 2 (3.0) 1 (1.7) 3 (4.8)

PR 15 (22.4) 22 (36.7) 20 (32.3)

SD 27 (40.3) 25 (41.7) 27 (43.5)

PD 15 (22.4) 7 (11.7) 7 (11.3)

NE 8 (11.9) 5 (8.3) 4 (6.5)

16-week DCR rate, n (%) [95%CI] 39 (58.2) [45.5, 70.2] 49 (81.7) [69.9, 90.5] 48 (77.4) [65.0, 87.1]

mDoR, mo (95%CI) [range]NR (2.3, NA)

[0.0+ to 17.5+]

12.9 (6.7, NA)

[0.0+ to 16.9+]

NR (9.0, NA)

[1.9+ to 18.4+]

29




PFS by investigator assessment

Durvalumab

Durvalumab +

oleclumab

Durvalumab +

monalizumab

Events/patients, n 38/67 22/60 21/62

mPFS, mo (95%CI) 6.3 (3.7, 11.2) NR (10.4, NE) 15.1 (13.6, NE)

HR (95%CI) – 0.44 (0.26, 0.75) 0.66 (0.49, 0.85)

PF

S p

rob

abili

ty

1.0

0.8

0.6

0.4

0.2

0

Time, months

20181614121086420

No. at risk

037913162032325067

0591322303740464960

1161125354144465562

D

D + O

D + M

72.7%

64.8%

39.2%

Durvalumab + oleclumab (n=60)

Durvalumab + monalizumab (n=62)

Durvalumab (n=67)

30



• Conclusions

– In patients with stage III NSCLC, combined immunomodulation therapy including durvalumab provided

additional ORR and PFS benefit over durvalumab monotherapy, with no new safety signals reported


TEAEs occurring in >15% of patients in

any arm, n (%)

Durvalumab

(n=66)

Durvalumab + oleclumab

(n=59)

Durvalumab + monalizumab

(n=61)

All grades Grade 3/4 All grades Grade 3/4 All grades Grade 3/4

≥1 TEAE 65 (98.5) 23 (34.8) 57 (96.6) 21 (35.6) 61 (100) 16 (26.2)

Cough 12 (18.5) 0 18 (30.5) 1 (1.7) 27 (44.3) 0

Dyspnoea 17 (25.8) 2 (3.0) 15 (25.4) 1 (1.7) 14 (23.0) 1 (1.6)

Pruritus 7 (10.6) 0 10 (16.9) 0 15 (24.6) 0

Asthenia 10 (15.2) 0 10 (16.9) 0 14 (23.0) 0

Hypothyroidism 10 (15.2) 0 9 (15.3) 0 12 (19.7) 0

Diarrhoea 7 (10.6) 1 (1.5) 7 (11.9) 0 12 (19.7) 0

Pneumonitis 11 (16.7) 0 11 (18.6) 0 10 (16.4) 1 (1.6)

Arthralgia 11 (16.7) 0 9 (15.3) 0 10 (16.4) 0

Pyrexia 6 (9.1) 0 8 (13.6) 0 10 (16.4) 0

Rash 6 (9.1) 0 9 (15.3) 0 8 (13.1) 0

Constipation 10 (15.2) 0 4 (6.8) 0 2 (3.3) 0

31

LBA44: Primary results of a randomized phase II study of osimertinib plus bevacizumab versus osimertinib monotherapy for untreated patients with non-squamous non-small-cell lung cancer harboring EGFR mutations; WJOG9717L study – Kenmotsu H, et al

• Study objective

– To evaluate the efficacy and safety of 1L osimertinib + bevacizumab in patients with advanced EGFR+, non-

squamous NSCLC

Kenmotsu H, et al. Ann Oncol 2021;32(suppl):Abstr LBA44

Primary endpoint

• PFS (BICR)

Secondary endpoints

• PFS by investigator, ORR, OS, safety

R

1:1

Stratification

• Sex

• Clinical stage (IIIB-IV vs. recurrence)

• EGFR mutation (Del19 deletion vs. L858R)


• Advanced/recurrent, non-

squamous, NSCLC

• EGFR mutation positive

• Treatment naïve

• No symptomatic CNS

metastasis

• ECOG PS 0–1

(n=122)

Osimertinib 80 mg/day

(n=61)

Osimertinib 80 mg/day +

bevacizumab 15 mg/kg q3w

(n=61)

32


• Key results


PFS by BICR

Osimertinib

(n=61)

Osimertinib + bevacizumab

(n=61)

No. of events 33 33

mPFS, mo (95%CI) 20.2 (11.79, NE) 22.1 (19.81, NE)

1-year PFS rate, % (95%CI) 63.7 (49.5, 74.9) 73.8 (60.4, 83.3)

2-year PFS rate, % (95%CI) 44.5 (31.0, 57.2) 49.8 (36.1, 62.1)

Median follow-up: 30.4 months

HR 0.862 (60%CI 0.700, 1.060), (95%CI 0.531,1.397)

p=0.213 (one-sided)

Pro

gre

ssio

n-f

ree s

urv

iva

l

by t

he

BIC

R, %

100

75

50

25

0

Time, months

4842363024181260No. at risk

(censored)0 (28)17 (12)23 (8)27 (8)34 (7)47 (5)61 (0)

0 (28)20 (10)27 (6)36 (6)40 (6)54 (3)61 (0)

Osi

Osi + bev

Osimertinib

(n=61)

Osimertinib +

bevacizumab

(n=61)

mPFS by investigator, mo (95%CI) 17.1 (11.66, 30.62) 24.3 (20.01, 32.36)

1-year PFS, % (95%CI) 60.6 (46.9, 71.8) 77.8 (64.9, 86.5)

2-year PFS, % (95%CI) 39.8 (27.3, 52.0) 51.3 (37.7, 63.3)

ORR, % (95%CI) 86 (77, 96) 82 (72, 92)

mOS, mo (95%CI) NE (33.8, NE) NE (33.3, NE)

1-year OS, % (95%CI) 98.3 (88.8, 99.8) 90.2 (74.9, 99.5)

2-year OS, % (95%CI) 76.4 (63.5, 85.3) 81.7 (69.5, 89.5)

33



• Conclusions

– In patients with non-squamous, EGFR+ NSCLC, 1L osimertinib + bevacizumab failed to provide a significant

improvements in efficacy compared with osimertinib alone


TEAEs, n (%)Osimertinib

(n=60)

Osimertinib +

bevacizumab

(n=61)

Grade 3–5 29 (48.3) 34 (55.7)

Led to discontinuation 16 (26.7) 34 (55.7)

Led to dose modification 25 (41.7) 39 (63.9)

Led to dose reduction 0 3 (4.9)

Led to death 0 0

SAEs 12 (20.0) 20 (32.8)

Led to discontinuation 3 (5.0) 7 (11.5)

Osimertinib Osimertinib +

bevacizumabHR (95%CI)

Ever-smoker, n 31 23

mPFS, mo (95%CI) 13.6 (7.8, 19.9) 32.4 (19.8, NE) 0.481 (0.227, 1.019)

Never-smoker, n 30 38

mPFS, mo (95%CI) 32.5 (13.8, NE) 20.3 (13.7, 32.3) 1.444 (0.736, 2.833)

Exon 19 del, n 36 35

mPFS, mo (95%CI) 20.3 (9.6, NE) NE (20.1, NE) 0.622 (0.312, 1.240)

Exon 21 L858R, n 25 26

mPFS, mo (95%CI) 15.7 (11.5, 32.5) 20.0 (8.5, 24.4) 1.246 (0.621, 2.502)

34

LBA46: Efficacy and safety of poziotinib in treatment-naïve NSCLC harboring HER2 exon 20 mutations: a multinational phase 2 study (ZENITH20-4) – Cornelissen R, et al

• Study objective

– To evaluate the efficacy and safety of poziotinib in patients with EGFR or HER2 exon 20-mutated NSCLC in

the ZENITH20-4 study

Cornelissen R, et al. Ann Oncol 2021;32(suppl):Abstr LBA46

Primary endpoint

• ORR

Secondary endpoints

• DCR, DoR, safety


• EGFR or HER2 exon 20

insertion

• Treatment naïve/previously

treated

Poziotinib 16 mg/daya

(n=48)

Cohort 1: Previously treated; EGFR

exon 20 insertion NSCLC

Cohort 3: Treatment naïve; EGFR


Cohort 5: Exploratory of Cohorts 1–4

Cohort 2: Previously treated; HER2


Cohort 7: Atypical EGFR or HER2

mutation

Cohort 6: EGFR osimertinib failure

Cohort 4: Treatment naïve; HER2


aDose reduced to 8 mg BID for patients still enrolling

35


• Key results


Poziotinib 16 mg/day

(n=48)

ORR, n (%) [95%CI] 21 (43.8) [29.5, 58.8]

BOR, n (%)

CR 1 (2.1)

PR 20 (41.7)

SD 15 (31.3)

PD 7 (14.6)

NE 5 (10.4)

DCR, n (%) 36 (75.0)

mPFS, mo (range) 5.6 (0–20.2+)

PFS duration, %

>6 months

>12 months

42

26

Duration of response

Su

rviv

al p

rob

ab

ility

1.0

0.8

0.6

0.4

0.2

0

Time, months

211815129630

0114572021No. at risk

Censored

mDoR, mo (range) 5.4 (2.8–19.1+)

Median follow-up of response, mo 13.5

Response duration, %

>6 months

>12 months

42

24

36



• Conclusions

– In patients with NSCLC and HER2 exon 20 mutations, 1L poziotinib demonstrated promising antitumor

activity and had a manageable safety profile


AEs, n (%) Any grade Grade 3

Diarrhoea 40 (83) 7 (15)

Rash 34 (69) 17 (35)

Stomatitis/mucosal inflammation 39 (81) 10 (21)

Paronychia 22 (46) 4 (8)

Pneumonitis 2 (4) 1 (2)

TRAEs, n (%)Poziotinib 16 mg/day

(n=48)

Any 48 (100)

Serious 5 (10)

Led to interruption 42 (88)

Led to dose reduction 37 (77)

Led to discontinuation 6 (13)

37

LBA50: A randomized phase III study comparing cisplatin-pemetrexed (cis-pem) with carboplatin (C)-paclitaxel (P)-bevacizumab (B) in chemotherapy naïve patients (pts) with advanced KRAS mutated non-small cell lung cancer (NSCLC): NVALT22 – Dingemans AC, et al

• Study objective

– To evaluate the efficacy and safety of carboplatin + paclitaxel + bevacizumab in patients with advanced,

KRAS-mutated NSCLC compared with standard of care in the NVALT22 study

Dingemans AC, et al. Ann Oncol 2021;32(suppl):Abstr LBA50

Primary endpoint

• PFS

Secondary endpoints

• ORR, DCR, OS, safety

R

1:1

Pemetrexed

maintenance

Bevacizumab

maintenance

Stratification

• KRAS mutation (G12C vs. G12V vs. other)

• ECOG PS (0–1 vs. 2)

• Brain metastasis (yes vs. no)

• Prior anti-PD-L1 (yes vs. no)


• Advanced NSCLC

• KRAS mutation

• Chemotherapy naïve/previous

anti-PD-L1 therapy allowed

• ECOG PS 0–2

(n=240)Cisplatin 75 mg/m2 +

pemetrexed 500 mg/m2 q3w

(n=101)

Carboplatin AUC6 + paclitaxel 200 mg/m2 +

bevacizumab 15 mg/kg q3w

(n=102)

38


• Key results


PFS

Su

rviv

al p

rob

ab

ility

, %

100

75

50

25

0

Time, months

60544842363024181260

0

(10)

1

(9)

1

(9)

1

(9)

1

(9)

1

(9)

2

(8)

4

(8)

9

(8)

39

(6)

102

(0)

0

(9)

0

(9)

0

(9)

0

(9)

1

(8)

2

(8)

4

(8)

7

(7)

8

(7)

35

(5)

101

(0)

CPB

Cis-Pem

Events = 184

Stratified HR 0.96 (95%CI 0.70, 1.31); p=0.81

mPFS CPB 5.2 mo (95%CI 4.4, 6.2)

mPFS Cis-Pem 4.7 mo (95%CI 3.9, 5.9)

CPB

Cis-Pem

No. at risk

(censored)

39



• Conclusions

– In patients with advanced KRAS-mutated NSCLC, carboplatin + paclitaxel + bevacizumab failed to

demonstrate improved PFS compared with cisplatin + pemetrexed and had a safety profile similar to

previous findings


Grade ≥3 TRAEs occurring

in ≥5% of patients, %

CPB

(n=100)

Cis-Pem

(n=98)

All

(n=198) p-value

Neutropenia 6 8 14 0.59

Infection 5 2 7 0.44

Hypertension 7 0 7 0.01

Nausea 2 4 6 0.44

Malaise 2 1 3 1

40

LBA51: EMPOWER-Lung 3: cemiplimab in combination with platinum doublet chemotherapy for first-line (1L) treatment of advanced non-small-cell lung cancer (NSCLC) – Gogishvili M, et al

• Study objective

– To evaluate the efficacy and safety of 1L cemiplimab + platinum-based chemotherapy in patients with

stage III/IV NSCLC without actionable mutations in the EMPOWER-Lung 3 study

Gogishvili M, et al. Ann Oncol 2021;32(suppl):Abstr LBA51

Primary endpoint

• OS

Secondary endpoints

PFS, ORR, DoR, BOR, PROs, safety

R

2:1

PD or 108

weeks


• Advanced, squamous/non-

squamous NSCLC (stage

IIIB/C–IV)

• Treatment-naïve

• No EGFR, ALK or ROS1

mutations

• Brain mets allowed if stable

• ECOG PS 0–1

(n=466)

Placebo +

platinum-doublet chemotherapya q3w

(4 cycles)

(n=152)

Cemiplimab 350 mg +

platinum-doublet chemotherapya q3w

(4 cycles)

(n=312)

aInvestigator choice; pemetrexed maintenance mandatory for patients with non-squamous

NSCLC who received a pemetrexed-containing regimen

Stratification

• PD-L1 expression (<1% vs. 1–49% vs ≥50%)

• Histology (non-squamous vs. squamous)

41


• Key results


Overall survival

Patients,

n

Events,

n (%)

mOS, mo

(95%CI)

Cemiplimab + chemo 312 132 (42.3) 21.9 (15.5, NE)

Placebo + chemo 154 82 (53.2) 13.0 (11.9, 16.1)

Pro

ba

bili

ty o

f O

S

1.0

0.8

0.6

0.4

0.2

0

26242220181614121086420

No. at risk

008185286131162199233256269289312

Time, months

0025142646658598112126141154

Cemiplimab +

chemotherapy

Placebo +

chemotherapy

12-mo OS, % (95%CI)

65.7 (59.9, 70.9)

vs.

56.1 (47.5, 63.8)

HR 0.71 (95%CI 0.53, 0.93); p=0.014

Progression-free survival

Pro

ba

bili

ty o

f P

FS

1.0

0.8

0.6

0.4

0.2

0

26242220181614121086420

000215275790113145194248280312

Time, months

0001161116243464106133154

12-mo PFS, % (95%CI)

38.1 (32.4, 43.8)

vs.

16.4 (10.5, 23.4)

HR 0.56 (9%%CI 0.44, 0.70); p<0.0001

Patients,

n

Events,

n (%)

mPFS, mo

(95%CI)

Cemiplimab + chemo 312 204 (65.4) 8.2 (6.4, 9.3)

Placebo + chemo 154 122 (79.2) 5.0 (4.3, 6.2)

No. at risk

Cemiplimab +

chemotherapy

Placebo +

chemotherapy

Median duration of follow-up (range): 16.4 mo (8.5–24.0)

42




Cemiplimab + chemo Placebo + chemo OS

n OS events/ n patients n OS events/ n patients HR (95%CI)

All patients 132/312 82/154 0.71 (0.53, 0.93)

Age group <65 years 72/184 53/94 0.57 (0.40, 0.81)

≥65 years 60/128 29/60 0.88 (0.56, 1.37)

Gender Male 113/268 75/123 0.55 (0.41, 0.74)

Female 19/44 7/31 2.11 (0.89, 5.03)

Race White 116/267 76/138 0.67 (0.50, 0.89)

Non-white 16/45 6/16 0.79 (0.31, 2.02)

Histology Squamous 57/133 39/67 0.56 (0.37, 0.84)

Non-squamous 75/179 43/87 0.79 (0.54, 1.14)

PD-L1 level <1% 54/95 27/44 1.01 (0.63, 1.60)

1–49% 40/114 31/61 0.52 (0.32, 0.83)

≥50% 38/103 24/49 0.61 (0.37, 1.02)

ECOG PS 0 11/51 6/18 0.55 (0.20, 1.49)

1 119/259 75/134 0.69 (0.52, 0.92)

Region Europe 118/270 76/138 0.67 (0.50, 0.90)

Asia 14/42 6/16 0.72 (0.27, 1.88)

Brain metastasis Yes 11/24 5/7 0.42 (0.14, 1.26)

No 121/288 77/147 0.68 (0.51, 0.90)

Cancer stage Locally advanced 16/45 13/24 0.54 (0.25, 1.15)

Metastatic 116/267 69/130 0.69 (0.51, 0.93)

Smoking Smokers 115/269 75/130 0.61 (0.46, 0.82)

Never smokers 17/43 7/24 1.28 (0.53, 3.08)

0.1 1 10Cemiplimab + chemo better Placebo + chemo better

43



• Conclusions

– In patients with advanced NSCLC, 1L cemiplimab + platinum-based chemotherapy demonstrated significant

clinical benefit and improvement in OS and PFS, with a manageable safety profile


n (%)

Cemiplimab + chemo

(n=312)

Placebo + chemo

(n=153)

Median duration of

exposure, weeks

(range)

38.5 (1.4–102.6) 21.3 (0.6–95.0)

TEAEs Any grade Grade 3–5 Any grade Grade 3–5

Overall 299 (96) 136 (44) 144 (94) 48 (31)

Led to discontinuation 16 (5) 13 (4) 4 (3) 4 (3)

Led to death 19 (6) 19 (6) 12 (8) 12 (8)

n (%)

Cemiplimab + chemo

(n=312)

Placebo + chemo

(n=153)

TRAEs

Overall 275 (88) 90 (29) 129 (84) 28 (18)

Led to discontinuation 10 (3) 7 (2) 1 (1) 1 (1)

Led to death 4 (1) 4 (1) 1 (1) 1 (1)

irAEs

Overall 59 (19) 9 (3) - -

TRAEs 3 (1) 3 (1) - -

Led to discontinuation 1 (0.3) 1 (0.3) - -

44

1171MO: PACIFIC-R real-world study: treatment duration and interim analysis of progression-free survival in unresectable stage III NSCLC patients treated with durvalumab after chemoradiotherapy – Girard N, et al

• Study objective

– To evaluate the efficacy and safety of durvalumab in patients with unresectable, stage III NSCLC in a real-life

setting in the PACIFIC-R study

Girard N, et al. Ann Oncol 2021;32(suppl):Abstr 1171MO

Primary endpoint

• PFS, OS

Secondary endpoints

• DCR, safety

PD/

up to 5 years

Retrospective data collection from

medical records


• Unresectable stage III NSCLC

• Any PD-L1 status

• No PD following platinum-

based chemotherapy

(n=1399)

Durvalumab 10 mg/kg q2w

45


• Key results


PACIFIC-R FAS

(n=1339)

PACIFIC trial (durvalumab arm)

(n=476)

Total events, n (%) 737 (52.7) 268 (56.3)

Progression per RECIST, n (%) 456 (32.6)

Progression per physician assessment, n (%) 170 (12.2)

Progression, assessment unknown, n (%) 30 (2.1)

Deaths in absence of progression, n (%) 81 (5.8)

mPFS, mo (95%CI) 21.7 (19.2, 24.5) 16.9 (13.0, 23.9)

PFS rate, %

12-mo 62.4 55.7

24-mo 48.2 45.0

46




mPFS, mo (95%CI)

PD-L1 ≥1% 22.4 (18.7, 25.5)

PD-L1 <1% 16.3 (11.7, 23.2)

Inconsistenta 25.2 (14.0, 27.3)

93 68 60 49 27 2 0

Histology mPFS, mo (95%CI)

Non-squamous 25.3 (22.0, 26.9)

Squamous 14.7 (12.8, 19.0)

No. at risk

PD-L1 ≥1%

PD-L1 <1%

Inconsistenta

Pro

ba

bili

ty o

f P

FS

0

0.2

0.4

0.6

0.8

1.0

0 6 12 18 24 30 36

Time, months

701 556 430 349 145 24 0173 131 99 77 38 7 0

PD-L1

No. at risk

Non-squamous

Squamous

Pro

ba

bili

ty o

f P

FS

Time, months

882 689 564 464 220 30 0496 384 279 220 90 19 0

0

0.2

0.4

0.6

0.8

1.0

0 6 12 18 24 30 36

mPFS, mo (95%CI)

Stage IIIA 23.7 (20.2, 26.5)

Stage IIIB/C 19.2 (15.8, 24.2)

mPFS, mo (95%CI)

Concurrent 23.7 (20.1, 25.8)

Sequential 19.4 (12.4, 25.3)

0

0.2

0.4

0.6

0.8

1.0

No. at risk

Concurrent

Sequential

Time, months

1071 842 672 548 245 41 0200 151 111 91 45 2 0

0 6 12 18 24 30 36

Pro

ba

bili

ty o

f P

FS

CRT Type

0

0.2

0.4

0.6

0.8

1.0

Pro

ba

bili

ty o

f P

FS

Stage

No. at risk

Stage IIIA

Stage IIIB/C

Time, months

604 490 391 316 134 16 0714 533 413 337 165 29 0

0 6 12 18 24 30 36

aTested but not clearly reported

47



• Conclusions

– In patients with unresectable stage III NSCLC, real-world data on the effect of durvalumab after

chemotherapy were consistent with those observed in the PACIFIC trial


FAS (n=1399)

Discontinuation

reason,

n (%)

Median time from

durvalumab start to

discontinuation,

months

Patient decision 20 (1.4) 6.1

AE 233 (16.7) 2.8

Completed treatment 659 (47.1) 12.0

Disease progression 377 (26.9) 5.1

Death 21 (1.5) 1.9

Pneumonitis/ interstitial lung

disease, n (%)

FAS

(n=1399)

Any 250 (17.9)

Mild 56 (4.0)

Moderate 118 (8.4)

Severe 41 (2.9)

Life-threatening or fatal 5 (0.4)

48

1281O: Atezolizumab (atezo) vs platinum-based chemo in blood-based tumour mutational burden–positive (bTMB+) patients (pts) with first line (1L) advanced/metastatic (m)NSCLC: results of the Blood First Assay Screening Trial (BFAST) phase 3 cohort C – Dziadziuszko R, et al

• Study objective

– To evaluate the use of blood-based TMB as a predictive biomarker for immunotherapy in patients with

NSCLC in the BFAST study

Dziadziuszko R, et al. Ann Oncol 2021;32(suppl):Abstr 1281O

Primary endpoint

• PFS (RECIST v1.1, investigator assessed)

Secondary endpoints

• OS, ORR, DoR, safety

R

1:1

PD/loss of

benefit

PD/loss of

benefit

Stratification

• ECOG PS (0 vs. 1)

• Histology (SQ vs. non-SQ)

• Tissue availability (yes vs. no)

• bTMB status (moderate [10–15] vs. high [≥16])


• Unresectable stage IIIB–IV

NSCLC

• bTMB positive (≥10% cut-off)

• No EGFR/ALK alterations

• ECOG PS 0–1

(n=472)Platinum-based chemotherapy

q3w (4 or 6 cycles)*

(n=146)

Atezolizumab 1200 mg q3w

(n=145)

*Maintenance pemetrexed permitted for patients with non-squamous NSCLC

49


• Key results


PF

S, %

0 2 4 6 8 10 12 14 16 18 20 22 24 26 28

0

20

40

60

80

100

Time, monthsNo. at risk

Atezo 145 101 83 54 46 32 25 18 10 9 5 4 3 2 1

Chemo 146 113 81 38 15 11 6 3 3 1 0 0 0 0 0

PFS Atezo (n=145) Chemo (n=146)

Events, n (%) 119 (82) 124 (85)

mPFS, mo (95%CI) 4.5 (3.9, 5.6) 4.3 (4.2, 5.5)

Stratified HR (95%Cl); p-value 0.77 (0.59, 1.00); 0.053

OS

, %

0 2 4 6 8 10 12 14 16 18 20 22 24 26 28

0

20

40

60

80

100


Atezo 145 131 109 93 81 67 55 44 33 29 20 14 7 4 1

Chemo 146 129 115 93 76 62 43 35 29 22 17 12 11 2 0

OS Atezo (n=145) Chemo (n=146)

Events, n (%) 82 (57) 88 (60)

mOS, mo (95%CI) 13.3 (6.6, 18.4) 10.3 (8.5, 13.8)

Stratified HR (95%Cl); p-value 0.87 (0.64, 1.17); 0.35

Atezo

Chemo

Atezo

Chemo

PFS and OS in the bTMB ≥16 population

50



• Conclusions

– In patients with NSCLC selected by bTMB, atezolizumab monotherapy showed no significant improvement in

PFS or OS compared with platinum-based chemotherapy


AEs, n (%)Atezolizumab

(n=234)

Chemotherapy

(221)

Any grade, all cause

Grade 3/4

Grade 5

216 (92.3)

107 (45.7)

13 (5.6)

216 (97.7)

127 (57.5)

12 (5.4)

Any grade TRAE

Grade 3/4

Grade 5

138 (59.0)

43 (18.4)

0

194 (87.8)

102 (46.2)

3 (1.4)

Any grade serious AE

Serious TRAEs

104 (44.4)

27 (11.5)

82 (37.1)

32 (14.5)

Any grade led to discontinuation 23 (9.8) 44 (19.9)

Any grade AESI

Grade 3/4

95 (40.6)

29 (12.4)

58 (26.2)

10 (4.5)

AESI requiring corticosteroids 41 (17.5) 20 (9.0)

Advanced NSCLCNot radically treatable stage III and stage IV

Later lines

52

LBA45: Primary data from DESTINY-Lung01: a phase 2 trial of trastuzumab deruxtecan (T-DXd) in patients (pts) with HER2-mutated (HER2m) metastatic non–small cell lung cancer (NSCLC) – Li BT, et al

• Study objective

– To evaluate the efficacy and safety of trastuzumab deruxtecan in patients with HER2-mutated NSCLC in the

DESTINY-Lung01 study

Li BT, et al. Ann Oncol 2021;32(suppl):Abstr LBA45

Primary endpoint

• ORR (ICR)

Secondary endpoints

• DCR, DoR, PFS, OS, safety

Cohort 1:

HER2-expressing (IHC3+ or IHC2+)

trastuzumab deruxtecan 6.4 mg/kg q3w

(n=90)


• Unresectable/metastatic non-

squamous NSCLC

• Relapsed/refectory to standard

treatment

• HER2 expressing or HER2-

activating mutation

• No prior HER2-targeted therapy

• CNS metastasis allowed

Cohort 2:

HER2-mutated

trastuzumab deruxtecan 6.4 mg/kg q3w

(n=91)

53


• Key results

– Efficacy was consistently observed across subgroups including those with asymptomatic baseline CNS

metastases (18/33 patients; ORR 54.5 [95%CI 36.4, 71.9])


Trastuzumab deruxtecan (n=91)

Confirmed ORR, n (%) [95%CI] 50 (54.9) [44.2, 65.4]

BOR, n (%)

CR 1 (1.1)

PR 49 (53.8)

SD 34 (37.4)

PD 3 (3.3)

NE 4 (4.4)

DCR, n (%) [95%CI] 84 (92.3) [84.8, 96.9]

mDoR, mo (95%CI) 9.3 (5.7, 14.7)

Median follow-up, mo (range) 13.1 (0.7–29.1)

54




Best percentage change of tumour size from baseline

Patients (n=85)

Kinase domain

Extracellular domain

40

20

0

–20

–40

–60

–80

–100Be

st p

erc

en

t ch

an

ge

fro

m b

ase

line

in s

um

of d

iam

ete

rs

2

1

2

0

I

2

0

I

2

0

I

8

S

2

0

I

8

S

2

0

I

2

0

I

2

0

I

2

0

I

2

0

I

2

0

I

1

9

S

8

S

2

0

I

2

0

I

2

0

I

2

0

I

2

0

I

2

0

I

1

9

S

2

0

S

2

0

I

2

0

I

2

0

I

2

0

I

2

0

S

2

0

I

2

0

I

2

0

I

2

0

I

2

0

I

2

0

I

2

0

I

2

0

I

2

0

I

2

0

I

2

0

I

2

0

I

2

0

I

2

0

I

2

0

I

2

0

I

2

0

I

2

0

I

2

0

I

2

0

I

2

0

I

2

0

S

2

0

I

2

0

I

2

0

I

2

0

I

2

0

I

2

0

I

2

0

I

2

0

I

2

0

I

8

S

2

0

I

2

0

I

1

9

S

2

0

I

2

0

I

2

0

I

2

0

I

2

0

I

2

0

I

2

0

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2

0

I

2

0

I

2

0

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2

0

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2

0

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2

0

I

2

0

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1

9

S

2

0

I

2

0

I

2

0

I

2

0

I

2

0

I

2

0

I

2

0

I

8

SHER2 mutation

(exon and subtype)

HER2 mutation domain location

HER2 protein

expression

2

+

1

+

2

+

2

+

1

+

2

+

2

+

2

+

2 3

+

0 2

+

3

+

2

+

2

+

0 0 2

+

1

+

2

+

0 2

+

2

+

0 3

+

3

+

2

+

0 0 3

+

2

+

I

3

+

2

+

3

+

1

+

2

+

1

+

3

+

2

+

2

+

2

+

2

+

3

+

2

+

2

+

2

+

3

+

2

+

2

+

02

+

HER2 gene

amplification

_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ + + _ + _ _ _ _ _ _ _ _ _ _ _ _ _ +_

Prior HER2 TKI therapy Y Y Y YYY Y Y Y Y Y Y

55




Progression-free survival

Pro

po

rtio

no

f p

atie

nts

, %

100

80

60

40

20

0

181614121086420 26242220

791315151919212531394249556974838991 011111127


mPFS 8.2 mo (95%CI 6.0, 11.9)

Overall survival

mOS 17.8 mo (95%CI 13.8, 22.1)100

80

60

40

20

0

Time, months

91 192225293646515865687075757782868889 5710131314151719 13 0

0 18161412108642 26242220 28 30

56



– Any grade TEAE ILD/pneumonitis was reported in 26.4% of patients, 75% were grade 1/2 and 2.2% were

grade 5

– TEAE ILD and pneumonitis led to discontinuation in 5.5% and 13.2% of patients, respectively

• Conclusions

– In previously treated patients with HER2-mutated NSCLC, trastuzumab deruxtecan demonstrated

encouraging activity and was generally well-toleratedLi BT, et al. Ann Oncol 2021;32(suppl):Abstr LBA45

TRAEs occurring in ≥20% of all patients, n (%)

Trastuzumab deruxtecan (n=91)

Any grade Grade ≥3

Nausea 66 (72.5) 8 (8.8)

Fatigue 48 (52.7) 6 (6.6)

Alopecia 42 (46.2) 0

Vomiting 36 (39.6) 3 (3.3)

Neutropenia 32 (35.2) 17 (18.7)

Anaemia 30 (33.0) 9 (9.9)

Diarrhoea 29 (31.9) 3 (3.3)

Decreased appetite 27 (29.7) 0

Leukopenia 21 (23.1) 4 (4.4)

Constipation 20 (22.0) 0

TEAEs, n (%)Trastuzumab deruxtecan

(n=91)

Any 88 (96.7)

Grade ≥3 42 (46.2)

Serious 18 (19.8)

Led to discontinuation 23 (25.3)

Led to dose reduction 31 (34.1)

Led to death 2 (2.2)

57

LBA47: Activity of OSE-2101 in HLA-A2+ non-small cell lung cancer (NSCLC) patients after failure to immune checkpoint inhibitors (IO): final results of phase 3 Atalante-1 randomised trial – Besse B, et al

• Study objective

– To evaluate the efficacy and safety of the anticancer vaccine OSE-2101 in patients with advanced HLA-A2+

NSCLC in the Atalante-1 study

– The study was stopped early in April 2020 due to COVID-19 pandemic and a new population of interest was

defined which included patients with secondary resistance after sequential immunotherapy

Besse B, et al. Ann Oncol 2021;32(suppl):Abstr LBA47

Primary endpoint

• OS

Secondary endpoints

• DCR, safety

R

2:1

PD/toxicity

PD/toxicity

Stratification

• Histology (SQ vs. NSQ)

• Best response to 1L (CR/PR vs. SD/PD)

• Line rank of prior ICI (1L vs. 2L)


• Advanced NSCLC

• Failure on platinum-based

chemotherapy and ICI

• Brain mets allowed if

asymptomatic

• ECOG PS 0–1

(n=103)

Standard of care

(docetaxel or pemetrexed)

(n=39)

OSE-2101 q3w for 6 doses then

q8w to year 1 then q12w

(n=64)

58


• Key results:


Overall survival in the new population of interest (post-hoc)

OS

pro

babili

ty

1.0

0.8

0.6

0.4

0.2

0

Time, months

3633302724211815129630

01446912203244597080

01235915242938

No. at risk

OSE-2101

SoC

Cut-off: 15 Jan 2021; median follow-up: 25 months

OSE-2101

(n=80)

SoC

(n=38)

Events, n (%) 61 (76) 34 (90)

mOS, mo (95%CI) 11.1 (8.6, 13.5) 7.5 (4.7, 10.3)

OSE-2101

SoC

HR 0.59 (95%CI 0.38, 0.91)

p-value stratified = 0.017

59



• Conclusions

– In patients with advanced HLA-A2+ NSCLC, OSE-2011 showed an interesting signal of activity in a specific

post-hoc restrictive subgroup of the ITT (118/219) and was generally well-tolerated

– Prospective validation of the signal is mandated


OSE-2101

(n=80)

SoC

(n=38)

Patients with measurable

lesions at baseline78 38

6-month DCR rate, n (%) 19 (25) 9 (24)OR 1.09 (95%CI 0.43, 2.75);

p=0.87

Objective response, n (%) 6 (8) 7 (18)OR 0.33 (9%%CI 0.10, 1.11);

p=0.07

mPFS, months (95%CI) 2.7 (1.6, 2.8) 3.2 (2.6, 4.7)HR 1.20 (95%CI 0.8, 1.8);

p=0.40

TRAEs, n (%)OSE-2101

(n=79)

SoC

(n=37)

All 60 (76) 29 (78)

Grade 3–5 9 (11) 13 (35)

Serious 9 (11) 3 (8)

Led to discontinuation 0 0

Led to death 0 0

60

LBA49: Efficacy of datopotamab deruxtecan (Dato-DXd) in patients (pts) with advanced/metastatic (adv/met) non-small cell lung cancer (NSCLC) and actionable genomic alterations (AGAs): preliminary results from the phase 1 TROPION-PanTumor01 study – Garon EB, et al

• Study objective

– To evaluate the efficacy and safety of datopotamab deruxtecan in patients with advanced NSCLC who

progressed after prior treatment in the TROPION-PanTumor01 study

Garon EB, et al. Ann Oncol 2021;32(suppl):Abstr LBA49

Primary endpoints

• MTD, safety

Secondary endpoints

• Efficacy, PK

Datopotamab deruxtecan

4 mg/kg (n=50)


6 mg/kg (n=50)


• Advanced or metastatic NSCLC

• Refractory to or relapsed on

standard treatment

• CNS metastasis allowed

• ECOG PS 0–1

(n=175)


8 mg/kg (n=80)

Data-DXd 0.27

to 10 mg/kg q3w

AGA subset analysis

(n=34)

Dose escalation Dose expansion

61


• Key results


Patients

Data-Dxd

(n=34)

ORR, n (%) 12 (35)

BOR, n (%)

CR 0

PR 12 (35)

SD 14 (41)

Non-CR/PD 2 (6)

PD 2 (6)

NE 4 (12)

mDoR, mo (95%CI) 9.5 (3.3, NE)

80

60

40

20

0

–20

–40

–60

–80

Best change in SOD (BICR) and tumour genotype

a b b b

Be

st ch

an

ge

in S

OD

fro

m b

ase

line

, %

Dose level

4 mg/kg

6 mg/kg

8 mg/kg

Actionable

genomic

alterations

TK

I w/o

osi

TK

I w/o

osi

TK

I inclo

si

TK

I inclo

si

TK

I inclo

si

TK

I inclo

si

TK

I

TK

I

TK

I

TK

I w/o

osi

TK

I

TK

I inclo

si

TK

I inclo

si

TK

I inclo

si

TK

I inclo

si

TK

I inclo

si

TK

I inclo

si

TK

I inclo

si

TK

I inclo

si

Other

EGFRm

Prior TKI

TK

I inclo

si

No

No

TK

I inclo

si

TK

I inclo

si

TK

I

TK

I

TK

I inclo

si

TK

I inclo

si

TK

I inclo

si

Ex19del

Ex20in

s

G719s

Ex19del

Ex19del

Ex19del

Ex19del

Ex19del

Ex19del

Ex19del

Ex19del

Ex19del

Ex19del

Ex19del

Ex19del

Ex20in

s

Ex20in

s

L858R

L858R

L858R

L858R

L858R

RO

S1

ALK

ALK

Negativ

e

Negativ

e

Unknow

n

ALK

L861Q

T790M

T790M

T790M

T790M

T7

90M

T7

90M

T7

90M

T7

90M

T7

90M

E700K

K714N

LM5R

T790M

E74G

aPateint NE; bpatients with unconfirmed PR

62



• Conclusions

– In heavily pretreated patients with advanced NSCLC, datopotamab deruxtecan demonstrated clinical

antitumor activity across different genomic alterations including EGFR and had a manageable safety profile


AEs, %


(n=34)

TEAE 100

Grade ≥3 53

TRAEs 88

Grade ≥3 38

Serious TEAEs 35

Grade ≥3 29

AEs, %


(n=34)

Dose adjustments

Led to discontinuation 15

Led to dose interruption 27

Led to dose reduction 15

Drug-related ILD 1

Grade ≤2 0

Grade 3/4 0

Grade 5 1

63

1191O: MRTX-500: phase 2 trial of sitravatinib (Sitra) + nivolumab (Nivo) in patients (pts) with nonsquamous (NSQ) non–small-cell lung cancer (NSCLC) progressing on or after prior checkpoint inhibitor (CPI) therapy – Leal TA, et al

• Study objective

– To evaluate the efficacy and safety of 2L or 3L sitravatinib + nivolumab in patients with non-squamous

NSCLC in the MRTX-500 study

Leal TA, et al. Ann Oncol 2021;32(suppl):Abstr 1191O

Primary endpoint

• ORR (RECIST v1.1)

Secondary endpoints

• DoR, CBR, PFS, OS, safety


• Advanced non-squamous NSCLC

• No driver mutations

• Anti-PD-L1 last treatment line

• CR, PR or SD ≥12 weeks from

prior treatment

• No uncontrolled brain mets

• ECOG PS 0–2

(n=68)

Sitravatinib 120 mg/day +

nivolumab

(n=68)

64




0 7 14 21 28 35 42

PRCR

PRSD

PDCR

SDPR

SDPR

PRPR

SDSD

SDSDSDSD

PRPR

SDSDSD

SDSD

SDSD

SDSD

PRSDSD

SDSDSD

SDSD

SDSD

PRSDSDSDSD

PDSD

SDSD

SDSD

PDSDPDSD

SDSDPD

SD

Duration of treatment (n=58)

Duration of treatment, months

Progression

First Response

Treatment Ongoing

Death

• ORR 18% (12/68), including 2 CRs (3%) and 10 PRs (15%)

– DCR 78% (53/68)

• mDoR 12.8 months

• Median duration of treatment:

– Sitravatinib: 4.8 mo (range: 0–40)

– Nivolumab: 5.2 mo (range: 0–41)

65


• Key results


Progression-free survival (n=68)

100

80

60

40

20

00 6 12 18 24 30 36 42

31%

45%

79%

Time, months

PF

S, %

OS

, %

56%

45%

32%

0 6 12 18 24 30 36 42

100

80

60

40

20

0

Time, months

Overall survival (n=68)

Sitravatinib + nivolumab

(n=68)

mPFS, mo (95%Cl) 5.7 (4.9, 7.6)

Events/censored, n (%) 53 (78)/15 (22)


(n=68)

mOS, mo (95%Cl) 14.9 (9.3, 21.1)

Events/censored, n (%) 46 (68)/22 (32)

No. at risk 68 25 10 4 3 2 1 0 No. at risk 68 52 34 26 16 11 4 0

66




TRAEs occurring in

≥15% of patients, %

Sitravatinib + nivolumab (n=68)

Any grade Grade 3/4

Any 93 66

Diarrhoea 62 16

Fatigue 52 4

Nausea 44 2

Hypertension 40 22

Decreased appetite 35 0

Weight decreased 31 9

Vomiting 31 0

Hypothyroidism 22 0

Dysphonia 19 0

ALT increased 18 2

AST increased 16 0

Stomatitis 15 2

PPE syndrome 15 3

Dehydration 15 3

TRAEs ≥15% of patients, %


(n=68)

Led to discontinuation 22

Sitravatinib 21

Nivolumab 9

Led to dose reduction of sitravatinib 60

80 mg 31

60 mg 22

40 mg 7

Led to ≥1 dose interruption of sitravatinib 81

67


• Conclusions

– In patients with non-squamous NSCLC, sitravatinib + nivolumab provided interesting activity signals and

promising outcomes at IO resistance, and no new safety signals were reported


68

1192MO: Amivantamab monotherapy and in combination with lazertinib in post-osimertinib EGFR-mutant NSCLC: analysis from the CHRYSALIS study – Leighl NB, et al

• Study objective

– To evaluate the efficacy and safety of amivantamab alone or combined with lazertinib after osimertinib failure

in patients with advanced, EGFR-mutant NSCLC P

Leighl NB, et al. Ann Oncol 2021;32(suppl):Abstr 1192MO

Primary endpoint

• ORR

Secondary endpoints

• DoR, PFS, OS, safety

Post-osimertinib

amivantamab

cohorta

(n=121) Key patient inclusion criteria

• Advanced NSCLC

• EGFR mutant

• Unresponsive to prior

treatmentCombination

Amivantamab

1050/1400 mg +

lazertinib 240 mg

or SOC chemo

Monotherapy

Amivantamab

1050/1400 mg

aMajor biomarker pre-selected (T790M+/-; C797S+/-;MET amplified; MET exon14

skipping; EGFR exon20 insertion); bbiomarker unselected

Post-osimertinib

amivantamab +

lazertinib cohortb

(n=45)

Post any EGFR TKI (T790M+, C797S+)

Post any EGFR TKI (T790M-, C797S-)

Post osimertinib (C797S+)

Post any EGFR TKI (MET amplified)

MET Exon 14 skipping

EGFR Exon20ins

AMI + LAZ

Post-osimertinib EGFRm NSCLC

AMI + SoC chemotherapy

Advanced NSCLC

69


• Key results

– ORR was higher among those with identified EGFR/MET-based osimertinib resistance receiving

amivantamab + lazertinib then amivantamab alone (47% vs. 18%)


Post-osimertinib amivantamab cohort

(n=121)

Post-osimertinib amivantamab + lazertinib cohort

(n=45)

BOR, % 27 36

Confirmed ORR, % (95%CI) 19 (12, 27) 36 (22, 51)

CR, n (%) 0 1 (2)

PR, n (%) 23 (19) 15 (33)

SD, n (%) 53 (44) 14 (31)

PD, n (%) 39 (32) 11 (24)

NE, n (%) 6 (5) 4 (9)

mDoR, months (95%CI) 5.9 (4.2, 12.6) 9.6 (5.3, NE)

CBR, % (95%CI) 48 (39, 57) 64 (49, 78)

mPFS, months (95%CI) 4.2 (3.2, 5.3) 4.9 (3.7, 9.5)

mF/U (range) 6.9 (0.7–38.6) 11.1 (1.0–15.0)

70



• Conclusions

– In patients with advanced EGFR-mutant NSCLC, amivantamab + lazertinib may have higher antitumor

activity than amivantamab alone with a safety profile consistent with previous findings


TEAEs occurring in ≥20% with

amivantamab monotherapy, n (%)

Amivantamab

(n=121)

Amivantamab + lazertinib cohort

(n=45)

Infusion-related reaction 83 (69) 35 (78)

Paronychia 45 (37) 22 (49)

Acneiform dermatitis 34 (28) 23 (51)

Hypoalbuminemia 31 (26) 17 (38)

Rash 32 (26) 12 (27)

Constipation 31 (26) 12 (27)

Nausea 29 (24) 20 (44)

Dyspnoea 28 (23) 11 (24)

Pruritus 27 (22) 14 (31)

71

1193MO: Amivantamab plus lazertinib in post-osimertinib, post-platinum chemotherapy EGFR-mutant non-small cell lung cancer (NSCLC): preliminary results from CHRYSALIS-2 – Shu CA, et al

• Study objective

– To evaluate the efficacy and safety of amivantamab alone or in combination with lazertinib in patients with

advanced, EGFR-mutant NSCLC

Shu CA, et al. Ann Oncol 2021;32(suppl):Abstr 1193MO

Primary endpoint

• ORR

Secondary endpoints

• CBR, DoR, PFS, OS, safety


• Advanced NSCLC

• EGFR Exon19del or L858R

(n=136)

Amivantamab

1050/1400 mg +

lazertinib 240 mgPlatinum-based

chemotherapy, osimertinib

or other (any number of prior

lines, any sequence)

Osimertinib (1L or 2L with

prior 1st/2nd gen EGFR TKI)

with platinum-based

chemotherapy as last line

Heavily pretreated

(n=56)

Target (3L/4L)

(n=80)

72


• Key results


NE NE

60

40

20

0

-20

-40

-60

-80

-100

PR SD PD

Best overall response in target populationa (n=29)

Ch

an

ge

fro

m b

ase

line in

So

Do

f ta

rge

t le

sio

ns,

% PR SD PD

Best overall response in heavily treated populationb (n=47)

60

40

20

0

-20

-40

-60

-80

-100

PD PD NE PDSD

CR

ORR 41% (95%CI 24, 61)

CBR 69% (95%CI 49, 85)

Median follow-up 4.6 mo (range 0.4–9.6)

ORR 21% (95%CI 11, 36)

CBR 51% (95%CI 36, 66)

Median follow-up 4.5 mo (range 0.3–9.7)

aPrevious treatment: 1/2L osimertinib + 1/2L EGFR TKI followed by platinum-based

chemotherapy; bno restrictions to prior treatment lines

Post-osimertinib amivantamab + lazertinib (n=136)

73



– Grade ≥3 TRAEs occurred in 50 (37%) patients, with the most common being infusion-related reaction (9%)

and dyspnoea (6%)

– Pneumonitis/ILD occurred in 4 (3%) patients

– AEs led of dose discontinuation (11%), dose reduction (18%) and dose interruption (46%)

• Conclusions

– In pretreated patients with advanced EGFR-mutant NSCLC, amivantamab + lazertinib demonstrated

favourable antitumor activity and was generally well-tolerated with no new safety signals reported


74

1194MO: Canakinumab (CAN) + docetaxel (DTX) for the second- or third-line (2/3L) treatment of advanced non-small cell lung cancer (NSCLC): CANOPY-2 phase III results – Paz-Ares L, et al

• Study objective

– To evaluate the efficacy and safety of canakinumab (a monoclonal anti-IL-1β antibody) + docetaxel in

patients with advanced NSCLC in the CANOPY-2 study

Paz-Ares L, et al. Ann Oncol 2021;32(suppl):Abstr 1194MO

Primary endpoint

• OS

Secondary endpoints

• PFS, ORR, DCR, DoR, PRO, safety

R

1:1

PD/

toxicity/

withdrawal

PD/

toxicity/

withdrawal

Stratification

• Histology (SQ vs. non-SQ)

• Best response to 1L (CR/PR vs. SD/PD)

• Line rank of prior ICI (1L vs. 2L)


• Stage IIIB–IV, squamous or non-

squamous NSCLC

• Prior chemotherapy + anti-PD-L1

• No EGFR or ALK mutations

• ECOG PS ≤1

(n=237)Placebo +

docetaxel 75 mg/m2 q3w

(n=117)

Canakinumab 200 mg q3w

+ docetaxel 75 mg/m2

(n=120)

75


• Key results


Overall survival Progression-free survival

Eve

nt-

fre

e p

rob

ab

ility

1.00

0.75

0.50

0.25

0

181614121086420


(no. of events)0

(73)

6

(72)

18

(69)

32

(65)

49

(55)

70

(47)

83

(34)

95

(23)

109

(9)

120

(0)

0

(68)

9

(67)

17

(62)

32

(60)

50

(51)

66

(43)

80

(31)

91

(20)

104

(7)

117

(0)

Can + Dtx

PBO + Dtx

6-mo OS

71% vs. 72%

12-mo OS

41% vs. 42%

mOS

10.5 vs. 11.3 mo

HR 1.06

(95%CI 0.76, 1.48)

One-sided p-value=0.63

Can + Dtx (n=120)

PBO + Dtx (n=117)

Eve

nt-

fre

e p

rob

ab

ility

1.00

0.75

0.50

0.25

0

1614121086420

Time, months

0

(100)

1

(100)

4

(99)

7

(98)

13

(95)

28

(81)

62

(51)

87

(27)

120

(0)

1

(94)

2

(94)

8

(91)

12

(88)

20

(83)

35

(71)

60

(47)

77

(31)

117

(0)

6-mo PFS

27% vs. 34%

12-mo PFS

8% vs. 12%

mPFS

4.2 vs. 4.2 mo

HR 1.12

(95%CI 0.85, 1.50)

Can + Dtx (n=120)

PBO + Dtx (n=117)

76



• Conclusions

– In patients with advanced NSCLC, the addition of canakinumab to chemotherapy did not provide

improvement in OS and PFS over chemotherapy alone and the safety profile was comparable to previous

findings


Canakinumab + docetaxel Placebo + docetaxel

AEs, n (%) Any grade Grade 3/4 Grade 5 Any grade Grade 3/4 Grade 5

Any grade 114 (95.0) 74 (61.7) 10 (8.3) 112 (98.2) 73 (64.0) 6 (5.3)

TRAEs 105 (87.5) 61 (50.8) 3 (2.5) 97 (85.1) 48 (42.1) 1 (0.9)

Serious AEs 55 (45.8) 41 (34.2) 10 (8.3) 50 (43.9) 39 (34.2) 6 (5.3)

Serious TRAEs 30 (25.0) 24 (20.0) 3 (2.5) 21 (18.4) 19 (16.7) 1 (0.9)

Led to discontinuation 28 (23.3) 11 (9.2) 7 (5.8) 33 (28.9) 12 (10.5) 3 (2.6)

Led to canakinumab/placebo discontinuation 16 (13.3) 8 (6.7) 7 (5.8) 12 (10.5) 6 (5.3) 3 (2.6)

AEs of special interest

Infections 59 (49.2) 18 (15.0) 8 (6.7) 47 (41.2) 18 (15.8) 2 (1.8)

Neutropenia 51 (42.5) 42 (35.0) 0 49 (43.0) 44 (38.6) 0

Thrombocytopenia 27 (22.5) 3 (2.5) 1 (0.8) 26 (22.8) 2 (1.8) 1 (0.9)

Other malignancies

SCLC, mesothelioma and thymic epithelial tumors

78

LBA61: Durvalumab ± tremelimumab + platinum-etoposide in first-line extensive-stage SCLC (ES-SCLC): 3-year overall survival update from the phase 3 CASPIAN study – Paz-Ares L, et al

• Study objective

– To evaluate the efficacy and safety of 1L etoposide + cisplatin/carboplatin ± durvalumab ± tremelimumab in

patients with ES-SCLC in the CASPIAN study

Paz-Ares L, et al. Ann Oncol 2021;32(suppl):Abstr LBA61

Primary endpoint

• OS

Secondary endpoints

• PFS, ORR, PROs, safety

Durvalumab 1500 mg + tremelimumab 75 mg

+ etoposide-platinum* q3w (4 cycles)

(n=268)

R

1:1:1

Etoposide-platinum* q3w (up to 6 cycles)

(n=269)

Durvalumab 1500 mg +

etoposide-platinum* q3w (4 cycles)

(n=268)Key patient inclusion criteria

• ES-SCLC


• Asymptomatic/stable CNS

metastases

• WHO PS 0–1

(n=805; 414 for HLA-I/II genotyping)

PD

PD

Durvalumab

1500 mg q4w

Durvalumab

1500 mg q4w

Optional PCI

Stratification

• Platinum agent (carboplatin vs. cisplatin)

*Etoposide 80–100 mg/m2 + carboplatin AUC5–6 or cisplatin 75–80 mg/m2

79


• Key results


3-year overall survival update: D + EP vs. EP

D + EP EP

Events 221/268 (82.5) 248/269 (92.9)

mOS, mo (95%CI) 12.9 (11.3, 14.7) 10.5 (9.3, 11.2)

HR (95%CI) 0.71 (0.60, 0.86)

Nominal p-value 0.0003

Median follow-up in censored patients:

39.4 months (range 0.1–47.5)

OS

pro

ba

bili

ty

1.0

0.8

0.6

0.4

0.2

0

Time, months

51484542393633302724211815129630

No. at risk

003132539465054607085109140177214244268

0003101317192436516482104156212243269

D + EP

EP

52.8%

32.0%22.9%

17.6%

5.8%13.9%

24.8%39.3%

3-year overall survival update: D + T + EP vs. EP

D + T + EP EP

Events 226/268 (84.3) 248/269 (92.2)

mOS, mo (95%CI) 10.4 (9.5, 12.0) 10.5 (9.3, 11.2)

HR (95%CI) 0.81 (0.67, 0.97)

Nominal p-value 0.0200

0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48

0

0.2

0.4

0.6

0.8

1.0

43.5%

30.6%22.9%

15.3%39.3%

24.8%

13.9%5.8%

D + T + EP 268 238 200 156 114 92 80 70 60 56 48 41 37 26 11 2 0

EP 269 243 212 156 104 82 64 51 36 24 19 17 13 10 3 0 0

Median follow-up in censored patients:

39.4 months (range 0.1–47.5)

Time, months

OS

pro

ba

bili

ty

No. at risk

80



• Conclusions

– In patients with ES-SCLC, 1L durvalumab + etoposide + cisplatin/carboplatin continued to demonstrate

survival benefit without any new safety concerns


TRAEs, n (%)

D + EP

(n=265)

D + T + EP

(n=266)

EP

(n=266)

Serious AE 86 (32.5) 126 (47.4) 97 (36.5)

Febrile neutropenia 12 (4.5) 11 (4.1) 12 (4.5)

Pneumonia 6 (2.3) 16 (6.0) 11 (4.1)

Anaemia 5 (1.9) 9 (3.4) 12 (4.5)

Thrombocytopenia 1 (0.4) 6 (2.3) 9 (3.4)

Hyponatremia 2 (0.8) 9 (3.4) 4 (1.5)

Neutropenia 2 (0.8) 5 (1.9) 7 (2.6)

Diarrhoea 2 (0.8) 7 (2.6) 4 (1.5)

Pulmonary embolism 1 (0.4) 7 (2.6) 0

Led to death 14 (5.3) 29 (10.9) 16 (6.0)

TRAEs led to death 6 (2.3) 12 (4.5) 2 (0.8)

81

LBA65: First-line nivolumab (NIVO) plus ipilimumab (IPI) vs chemotherapy (chemo) in patients (pts) with unresectable malignant pleural mesothelioma (MPM): 3-year update from CheckMate 743 – Peters S, et al

• Study objective

– To evaluate the long-term efficacy and safety of nivolumab + ipilimumab in patients with unresectable

malignant pleural mesothelioma in the CheckMate 743 study

Peters S, et al. Ann Oncol 2021;32(suppl):Abstr LBA65

Cisplatin or carboplatin + pemetrexed q3w

(6 cycles)

(n=302)

R

1:1

Nivolumab 3 mg/kg q2w +

ipilimumab 1mg/kg q6w (up to 2 years)


• Unresectable MPM


• ECOG PS 0–1

(n=605)

PD, toxicity

or 2 years

follow-up

Stratification

• Histology (epithelioid vs non-epithelioid)

• Gender

Primary endpoint

• OS

Secondary endpoints

• ORR, DCR, PFS (BICR), safety, biomarker analysis

82




NIVO + IPI

(n=303)

Chemo

(n=302) HR (95%CI)

mOS, mo 18.1 14.1 0.73 (0.61, 0.87)

mPFS, mo 6.8 7.2 0.92 (0.76, 1.11)

ORR, % 39.6 44.0

mDoR, mo 11.6 6.7

OS

, %

100

80

60

40

20

0


51 54484542393633302724211815129630

3-year update: overall survival in all randomized patients

2 0718354962738097116126145173200226251273303

0 06112033434654697697114138164192234269302

NIVO + IPI

Chemo

68%

41%

23%

58%

27%

15%

NIVO + IPI

Chemo

83




Epithelioid Non-epithelioid

NIVO + IPI

(n=229)

Chemo

(n=226)

mOS, mo 18.2 16.7

HR (95%Cl) 0.85 (0.69, 1.04)

NIVO + IPI

(n=74)

Chemo

(n=76)

mOS, mo 18.1 8.8

HR (95%Cl) 0.48 (0.34, 0.69)

OS

, %

100

80

60

40

20

0

0 6 12 18 24 30 36 42 48 54

Time, months

229 192 154 111 90 63 48 29 4 0NIVO + IPI

No. at risk

226 182 141 101 69 50 40 18 5 0Chemo

69%

66%

42%

33% 24%

19%

NIVO + IPI

Chemo

OS

, %

100

80

60

40

20

0

0 6 12 18 24 30 36 42 48 54

Time, months

74 59 46 34 26 17 14 6 3 0NIVO + IPI

No. at risk

76 52 23 13 7 4 3 2 1 0Chemo

63%

38%

22%NIVO + IPI

Chemo4%10%

33%

84


• Key results


NIVO + IPI

Low

(n=82)

High

(n=83)

mOS, mo 16.8 21.8

HR (95%CI) 0.57 (0.40, 0.82)

OS

, %

100

80

60

40

20

0


544842363024181260

01811142331486582

021124313846597283

Low

High

74%

49%

35%60%

30%

15%

Low

High

100

80

60

40

20

0

Time, months

544842363024181260

01611152338506482

0038111823366380

61%

28%

13%

46%

24%

11%

Low

High

OS

, %

Chemo

Low

(n=82)

High

(n=83)

mOS, mo 15.2 11.6

HR (95%CI) 1.14 (0.82, 1.59)

Overall survival by 4-gene inflammatory signature scorea

aIncluding CD8A, STAT1, LAG3, CD274 (PD-L1) genes

85




mOS, monthsUnstratified

HRSubgroup NIVO + IPI Chemo

Tissue TMB tertile

Low (n=103) 19.3 18.0 0.74

Intermediate (n=97) 17.9 9.9 0.48

High (n=95) 17.1 14.1 0.70

LIPI score

Good (n=293) 21.6 16.3 0.78

Intermediate (n=233) 17.1 14.1 0.76

Poor (n=47) 6.1 6.0 0.83

86



• Conclusions

– In patients with MPM, 1L nivolumab + ipilimumab demonstrated long-term benefit up to 3 years, irrespective

of histology, and had a favourable safety profile

– High 4-gene inflammatory signature and LIPI scores correlated with improved survival benefit for nivolumab +

ipilimumab


NIVO + IPI (n=300) Chemo (n=284)

TRAEs, % Any grade Grade 3/4 Any grade Grade 3/4

Any grade 80 31 82 32

Led to any treatment component discontinuation 23 15 16 7

Led to all treatment discontinuation 17 13 8 5

Serious 21 16 8 6

Led to death 1 <1

87

1732MO: Pembrolizumab and nintedanib for patients with advanced mesothelioma– Danios FX, et al

• Study objective

– To evaluate the efficacy and safety of nintedanib + pembrolizumab in patients with advanced malignant

mesothelioma

Danios FX, et al. Ann Oncol 2021;32(suppl):Abstr 1732MO


• Advanced pleural

mesothelioma

• Relapsed after platinum-

based chemotherapy

(n=30)

Nintedanib 150 mg BID

(n= 30)PD

Blood and tumour sample were

taken during treatment

Nintedanib 150 mg BID

+ pembrolizumab

200 mg q3w

(n= 30)

Induction Maintenance

88


• Key results


60

40

20

0

–20

–40

–60

–80

–100

Ch

an

ge

fro

m b

ase

line

, %

Best objective response

PD

SD

PR

DCR at 12 weeks 68.4%

(95%CI 43.4, 87.4)

IHC

PD-L1+ on tumour cells surface

Pe

rcen

tage

40

30

20

10

0No DCB DCB

BOR

PD

SD

PR

38

40

62

63

19

23

15

Pe

rcen

tage a

mo

ng

tota

l ce

lls

No DCB DCB

15

10

5

0

56

19

4045

Total CD45+

immune cells

No DCB DCB

6

4

2

0

19

4016

Total CD3+

T cells

55

30

Flow cytometry

Pe

rcen

tage a

mo

ng

CD

3+

ce

lls

No DCB DCB

15

10

5

0

56

55

Total CD8+

T cells

40

225018

55

3044

89



– The most common grade 3 AEs occurring in ≥5% of patients were fatigue (6.7%), dyspnoea (6.7%), skin

disorder (6.7%) and increased lipase (6.7%)

– Grade 5 myocarditis and cardiac disorder occurred in 1 (3%) patient

• Conclusions

– In patients with unresectable advanced MPM, nintedanib + pembrolizumab showed activity and had a

manageable safety profile

– Baseline tumour levels of PD-L1 and CD8+ T-cells were predictive of treatment response


90

LBA66: Efficacy and safety of nivolumab for patients with pre-treated type B3 thymoma and thymic carcinoma: results from the EORTC-ETOP NIVOTHYM phase II trial – Girard N, et al

• Study objective

– To evaluate the efficacy and safety of 2L nivolumab with or without ipilimumab in patients with advanced type

B3 thymoma or thymic carcinoma in the NIVOTHYM study

Girard N, et al. Ann Oncol 2021;32(suppl):Abstr LBA66

Cohort 2

Nivolumab 240 mg q2w +

ipilimumab 1mg/kg q6w

Cohort 1

Nivolumab 240 mg q2w


• Advanced/relapsed type B3

thymoma or thymic carcinoma

• Prior platinum-based

chemotherapy

(n=55)

Primary endpoint

• 6-month PFS rate (RECIST v1.1)

Secondary endpoints

• ORR, DCR, PFS, OS, safety

91


• Key results


NIVO (n=49)

n (%) By central review By local investigator

6-mo PFS rate

Success 17 (35) 19 (39)

Failure 32 (65) 30 (61)

95%CI 22, 50 25, 54

80%CI 26, 45 29, 49

Reason for failure

PD 24 24

Death without PD before 6 months 3 3

Start of new treatment before PD 1 -

Unknown disease status 4 3

92




NIVO (n=49)

BOR (investigator), n (%)

PR 6 (12)

SD 25 (51)

PD 13 (27)

NE 5 (10)

Response rate (CR + PR), % (95%CI) 12 (5, 25)

DCR (CR + PR + SD), % (95%CI) 63 (48, 77)

93




Progression-free survival Overall survival

Events/total mPFS, mo (95%CI)

34/49 6.0 (3.1, 10.4)

PF

S, %

100

80

60

40

20

0

Time, months242220181614121086420

No. at risk 1344679141723263449

OS

, %

100

80

60

40

20

0

Time, months

mOS, mo (95%CI)

21.3 (11.6, NE)

2826242220181614121086420

No. at risk 012479131518253039434749

94



– Grade 4/5 AEs included respiratory failure, neutropenia, myocarditis, immune-mediated transaminitis, sepsis

and dyspnoea

• Conclusions

– In patients with advanced type B3 thymoma or thymic carcinoma, 2L nivolumab monotherapy showed

survival benefit although failed to meet the primary endpoint for 6-month PFS rate

– The second cohort investigating nivolumab + ipilimumab combination is ongoing


Nivolumab (n=54)

n (%) Grade ≥1 Grade ≥3 Grade 4 Grade 5

All AEs 54 (100) 32 (59) 5 (9) 1 (2)

TRAEs 44 (81) 14 (26) 4 (7) -

esmo congress 2021

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