IASLC 2020 World Conference on Lung Cancer

Supported by Eli Lilly and Company.

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

Developed in association with theEuropean Thoracic Oncology Platform

28–31 January 2021

IASLC 2020 World Conference on Lung Cancer

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 2020. This slide set specifically focuses on the IASLC 2020 World

Conference on Lung Cancer 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 Solange Peters and Martin Reck 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 2020

Focus: NSCLC (all stages)

Dr Solange Peters

Multidisciplinary Oncology Center, Lausanne Cancer Center, Lausanne, Switzerland

Focus: Other malignancies, SCLC, mesothelioma, rare tumours

Dr Martin Reck

Department of Thoracic Oncology, Hospital Grosshansdorf, Grosshansdorf, Germany

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

PS01.02: National Lung Cancer Screening Program in Taiwan: The TALENT Study – Yang P-C, et al

• Study objective

– To assess the feasibility of a national lung cancer screening program for detecting lung cancer in never-

smokers with a high-risk in the Taiwan Lung Cancer Screening in Never-Smoker Trial (TALENT)

*2/7 days with cooking by pan-frying, stir-frying or deep-frying in

1 week (max. 21) x years with cooking Yang P-C, et al. J Thorac Oncol 2021;16(suppl):Abstr PS01.02

Bx/follow-up

Bx/follow-up

Key patient inclusion criteria

• Never smokers or former light smoker <10 pack-

years and had quit >15 years

• 55–75 years old

• One of following risks:

• Family history of lung cancer (≤3rd degree)

• Environmental tobacco smoking history

• Chronic lung disease (TB, COPD)

• Cooking index* ≥110

• Cooking without using ventilation

(n=12,011; 50% with a family history)

Low-dose chest CT

Biomarkers (blood, urine)

Questionnaire

Standard contrast-

enhanced chest CT

CXR

Positive

Negative

Positive

Positive

7


• Key results

*Ground glass opacity >5 mm, solid/part solid >6 mm Yang P-C, et al. J Thorac Oncol 2021;16(suppl):Abstr PS01.02

N=12,011

T0 lung cancer detection rate, % 2.6

Invasive lung cancer, % 2.1

Multiple primary lung cancer, % 17.9

LDCT positive*, % 17.4

Invasive procedures, % 3.4

Stage 0–I lung cancer confirmed, % 96.5

Prevalence of lung cancer, %

With family history

Without family history

3.2

2.0

Histologic diagnosis, n n=313

Adenocarcinoma in situ 58

Minimally invasive adenocarcinoma 71

Invasive adenocarcinoma 183

Adenosquamous carcinoma 1

Stage, n n=313

0 58

IA 218

IB 26

IIA 0

IIB 3

IIIA 2

IIIB 1

IV 5

Family history

(degree)

All lung

cancer, %

Invasive lung

cancer, %

0 2.0 1.6

1 3.1 2.5

2 4.0 3.7

3 6.7 5.3

≥4 9.1 9.1

p-value <0.001 <0.001

8


• Key results (cont.)

• Conclusions

– Using a national lung cancer screening program may be feasible to detect lung cancer in high-risk never-

smokers and those with a first-degree family history of lung cancer may be at increased risk

Yang P-C, et al. J Thorac Oncol 2021;16(suppl):Abstr PS01.02

Absence, n/N (%) Presence, n/N (%) RR (95%CI) p-value

Lung cancer family history 120/6002 (2.0) 193/6009 (3.2) 1.61 (1.28, 2.01) <0.001

First-degree relative 127/6432 (2.0) 186/5579 (3.3) 1.69 (1.35, 2.11) <0.001

Father 281/10,377 (2.7) 32/1634 (2.0) 0.72 (0.50, 1.04) 0.077

Mother 251/10,241 (2.5) 62/1770 (3.5) 1.43 (1.09, 1.88) 0.010

Brother 260/10,901 (2.4) 53/1110 (4.8) 2.00 (1.50, 2.67) <0.001

Sister 244/10,367 (2.4) 69/1644 (4.2) 1.78 (1.37, 2.32) <0.001

Second-degree relative 307/11,645 (2.6) 6/366 (1.6) 0.62 (0.28, 1.39) 0.238

Third-degree relative 312/11,947 (2.6) 1/64 (1.6) 0.60 (0.09, 4.20) 1.000

Environmental tobacco exposure 53/1999 (2.7) 254/9923 (2.6) 0.97 (0.72, 1.29) 0.813

Chronic lung disease history 284/10,568 (2.7) 19/1142 (1.7) 0.62 (0.39, 0.98) 0.038

Cooking index ≥110 209/7591 (2.8) 104/4395 (2.4) 0.86 (0.68, 1.08) 0.201

Cooking without ventilation 306/11,800 (2.6) 7/211 (3.3) 1.28 (0.61, 2.67) 0.513

9

OA07.06: Interdependence of KRAS and TP53 Mutations in Predicting ICI Efficacy in EGFR/ALK WT Non-Squamous NSCLC: Results From 1129 Patient-Level Data – Li L, et al

• Study objective

– To assess the interdependence of KRAS and TP53 mutations for predicting the efficacy of immune

checkpoint inhibitors in patients with EGFR or ALK WT nonsquamous NSCLC

• Methods

– Clinical and mutational data was collected from 1129 patients with EGFR or ALK WT nonsquamous NSCLC

who received immune checkpoint inhibitors from 8 cohorts (3DMed, SNCC, Van Allen, Rizvi-34, Rizvi-240,

MSKCC-75, MSKCC-350 and POPLAR/OAK)

– The impact of KRAS and TP53 mutations on ORR, PFS and OS was assessed

Li L, et al. J Thorac Oncol 2021;16(suppl):Abstr OA07.06

10


• Key results

– A longer PFS by immunotherapy, but not prolongation of PFS by chemotherapy, was found in patients with

TP53 and KRAS co-mutations although there was no association with TP53 or KRAS mutation alone


ORR, % mPFS, mo

TK (76) 50.0 10.48

T-only (209) 23.4 3.10

K-only (101) 16.7 2.77

WT (238) 14.3 3.23

Meta-cohort PFS

35302520151050

PF

S,

%

100

75

50

25

0

Log-rank p<0.001

Time, months

POPLAR/OAK PFS (docetaxel)

35302520151050

PF

S,

%

100

75

50

25

0

Log-rank p=0.032

Time, months

ORR, % mPFS, mo

TK (13) 7.7 2.86

T-only (82) 11.0 2.89

K-only (15) 13.3 2.86

WT (134) 18.7 4.30

11



• Conclusions

– In patients with nonsquamous NSCLC, the combination of KRAS and TP53 mutations are interdependent

for predicting the benefit of immune checkpoint inhibitors; better ORR and PFS was observed in those

who were EGFR/ALK WT


Totality Variable

ORR PFS OS

RR (95%CI) p-value RR (95%CI) p-value RR (95%CI) p-value

All TP53-mut vs. TP53-WT 1.94 (1.31, 2.87) 0.001 0.72 (0.55, 0.95) 0.019 1.21 (0.98, 1.50) 0.071

All KRAS-mut vs. KRAS-WT 1.54 (1.02, 2.32) 0.040 0.82 (0.56, 1.19) 0.295 1.01 (0.70, 1.47) 0.947

KRAS-mut TP53-mut vs. TP53-WT 2.86 (1.46, 5.57) 0.002 0.47 (0.32, 0.68) <0.001 0.75 (0.51, 1.12) 0.159

KRAS-WT TP53-mut vs. TP53-WT 1.53 (0.92, 2.56) 0.104 0.91 (0.65, 1.27) 0.566 1.47 (1.14, 1.91) 0.003

TP53-mut KRAS-mut vs. KRAS-WT 1.98 (1.17, 3.35) 0.011 0.66 (0.47, 0.93) 0.017 0.73 (0.51, 1.04) 0.078

TP53-WT KRAS-mut vs. KRAS-WT 1.28 (0.61, 2.71) 0.518 1.04 (0.60, 1.79) 0.885 1.19 (0.79, 1.77) 0.338

All TP53/KRAS-co-mut vs. rest 2.59 (1.63, 4.12) <0.001 0.58 (0.43, 0.79) 0.001 0.86 (0.62, 1.18) 0.356

12

OA07.08: HUDSON: An Open-Label, Multi-Drug, Biomarker-Directed, Phase II Platform Study in Patients with NSCLC, who Progressed on Anti-PD(L)1 Therapy – Besse B, et al

• Study objective

– To assess the efficacy and safety of durvalumab-based combinations in patients with metastatic NSCLC who

progressed on an anti-PD-(L)1-containing therapy

Besse B, et al. J Thorac Oncol 2021;16(suppl):Abstr OA07.08

Primary endpoint

• ORR

Secondary endpoints

• PFS, OS, DCR, safety

Durvalumab + ceralasertib (ATR)

Durvalumab + olaparib (PARP)Key patient inclusion criteria

• Locally advanced or

metastatic NSCLC

• Tumour progression on anti-

PD-(L)1

• Prior platinum-doublet

chemotherapy

• No EGFR, ALK, ROS1,

BRAF, MET or RET

alterations

(n=617)

Durvalumab + oleclumab (anti-CD73)

Durvalumab + trastuzumab deruxtecan (HER2)

Durvalumab + cediranib (VEGF)

Part A:

Biomarker

matched

(n=85)

Part B:

Biomarker

non-matched

(n=177)

Durvalumab + danvatirsen (STAT3)


Durvalumab + olaparib (PARP)


Durvalumab + danvatirsen (STAT3)





Durvalumab + trastuzumab deruxtecan (HER2)

ATM

STK11

CD73

HER2e

HRRm

HER2m

Primary

resistance

(n=74)

Acquired

resistance

(n=103)

13

Olaparib = PARP inhibitor, danvatirsen = STAT 3 inhibitor, ceralasertib = ATR inhibitor,

oleclumab = anti-CD73


• Key results


Progression-free survival Overall survival

015911153687

01381745

011312223962

0161657

Olaparib + durvalumab

Danvatirsen + durvalumab

Ceralasertib + durvalumab

Oleclumab + durvalumab

Time, months

Pro

ba

bili

ty o

f P

FS

1.0

0.8

0.6

0.4

0.2

0

211815129630

Time, months

Pro

babili

ty o

f O

S

1.0

0.8

0.6

0.4

0.2

0

302724211815129630

07918273442517387

02471219263445

02172336425562

03614294257

Olaparib + durvalumab

Danvatirsen + durvalumab

Ceralasertib + durvalumab

Oleclumab + durvalumab

No. at risk

14



• Conclusions

– In patients with NSCLC who have failed on anti-PD-(L1), use of molecular stratification is feasible

– Durvalumab + ceralasertib demonstrated preliminary promising activity


Durvalumab combination n ORR, n (%) mPFS, mo (80%CI) mOS, mo (80%CI)B

iom

ark

er

se

lec

ted

Olaparib HRR 21 2 (9.5) 2.79 (1.48, 5.26) 9.63 (5.26, 15.97)

Olaparib STK11 21 1 (4.8) 1.41 (1.38, 1.81) 5.75 (5.29, 10.84)

Ceralasertib ATM 18 2 (11.1) 7.43 (3.45, 9.46) 15.80 (11.01, NC)

Oleclumab 73H 23 0 (0) 1.58 (1.41, 2.76) 9.49 (7.49, NC)

Pri

ma

ry

res

ista

nce Olaparib 22 0 (0) 3.38 (2.10, 4.93) 7.16 (4.93, 10.28)

Danvatirsen 23 0 (0) 1.68 (1.64, 2.99) 6.01 (3.55, 6.51)

Ceralasertib 20 2 (10.5) 4.24 (1.94, 6.77) 11.60 (10.45, NC)

Oleclumab 9 0 (0) 1.41 (1.35, 1.81) 7.06 (4.90, 7.06)

Ac

qu

ire

d

res

ista

nce Olaparib 23 1 (4.3) 4.17 (2.69, 4.37) 15.51 (8.80, 19.75)

Danvatirsen 22 0 (0) 3.09 (2.83, 6.14) 11.20 (9.72, 12.55)

Ceralasertib 24 2 (8.3) 4.96 (3.55, 5.98) 17.38 (14.06, NC)

Oleclumab 25 1 (4.2) 2.63 (1.64, 2.79) 12.78 (6.14, 12.78)

15

MA08.10: LUNGMAP Master Protocol (LUNGMAP): Concordance Between Plasma ctDNA and Tissue Molecular Analysis – Mack PC, et al

• Study objective

– To assess the feasibility of using plasma ctDNA as a screening approach in patients with advanced NSCLC

• Methods

– Plasma samples and fresh tissue biopsies were collected from patients (n=129) undergoing LUNGMAP

screening for ctDNA testing using FoundationONE CDx and FoundationACT platforms

– Sensitivity was determined as the proportion of patients with drivers in both ctDNA and tissue and specificity

was determined as the proportion of patients without drivers in ctDNA and tissue using tissue-detected driver

alterations as the gold standard

Mack PC, et al. J Thorac Oncol 2021;16(suppl):Abstr MA08.10

16*Mostly point mutations


• Key results

– For cases with matched tissue and plasma, 54 of 129 patients had driver oncogenes (EGFR, KRAS, RET,

MET, BRAF) detected with a sensitivity of 83% and specificity of 97%


3.7

32.0

79.6

54.0

16.7 14.0

0%

20%

40%

60%

80%

100%

Driver only (n=54) Short variants*

Tissue only

Both

ctDNA only

Detection in ctDNA and tissue

17


• Conclusions

– The findings suggest that ctDNA can be used for enrolling patients in LUNGMAP sub-studies, particularly for

those with positive results although negative results should be considered inconclusive


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

19

PS01.04: International Tailored Chemotherapy Adjuvant Trial: ITACA Trial. Final Results – Novello S, et al

• Study objective

– To compare adjuvant pharmacogenomics-driven (tailored) chemotherapy, based on thymidylate synthase

(TS) and excision-repair cross-complementing-1 (ERCC1) gene expression versus standard adjuvant

chemotherapy

*Cisplatin-doublet, investigator choice Novello S, et al. J Thorac Oncol 2021;16(suppl):Abstr PS01.04

Primary endpoint

• OS (5-year rate)

Secondary endpoints

• RFS, safety

Stratification

• Stage II vs. III and smoking status

Profile 2: ERCC1 high, TS low

Profile 3: ERCC1 low, TS high

Profile 1: ERCC1 high, TS high


• Completely resected (R0)

NSCLC

• Stage II–IIIA

• ECOG PS 0–1

(n=733)

Profile 4: ERCC1 low, TS, low

Paclitaxel alone (n=148)

Control arm* (n=144)

Control arm* (n=47)

Control arm* (n=106)

Control arm* (n=92)

Pemetrexed alone (n=43)

Cisplatin-gemcitabine (n=101)

Cisplatin-pemetrexed (n=92)

Cisplatin not

allowed in the

tailored arm

Cisplatin

allowed in the

tailored arm

20


• Key results

Novello S, et al. J Thorac Oncol 2021;16(suppl):Abstr PS01.04

Overall survival Recurrence-free survival

Tailored arm (n=344) Control arm (n=346)

mRFS, months (95%CI) 64.4 (34.7, 96.4) 41.5 (29.2, 58.1)

HR (95%CI) 0.94 (0.74, 1.20)

Tailored arm (n=344) Control arm (n=346)

mOS, months (95%CI) 96.4 (81.8, NR) 83.5 (60.1, NR)

HR (95%CI) 0.76 (0.55, 1.04)

820354978108156239344

817334874110155221346Control

Pro

po

rtio

n o

f p

atie

nts

aliv

e

1.00

0.75

0.50

0.25

0

Time since randomisation, months96847260483624120

No. at risk

Tailored

Tailored

Control

O

68

86

E

78.5

75.5

Log-rank test

Chi2=2.864, p=0.091

81831447092126208344

81429406793128201346ControlP

rop

ort

ion o

f re

cu

rre

nce-f

ree

pa

tie

nts

1.00

0.75

0.50

0.25

0

Time since randomisation, months96847260483624120

No. at risk

Tailored

Tailored

Control

O

128

132

E

132.1

127.9

Log-rank test

Chi2=0.253, p=0.615

21




Overall survival Recurrence-free survivalOS / RFS

predictor

Age

<70 years

≥70 years

Sex

Male

Female

Smoking habit

Never/former smoker

Active smoker

ECOG PS

0

1

Stage

II

IIIA

Histology

Adeno CA

Squamous cell CA

Other

Primary surgery

Lobectomy

Pneumonectomy

Other

HR

(95%CI)

No. of OS events/

patients

Hazard

ratio

p-

value

0.5 1.0 1.5 2.0

110/533

44/157

114/474

40/214

79/341

75/349

111/515

36/156

88/406

66/282

91/407

51/239

12/43

106/475

30/97

11/58

0.80 (0.55, 1.17)

0.70 (0.39, 1.27)

0.79 (0.55, 1.14)

0.67 (0.36, 1.24)

0.64 (0.41, 1.00)

0.93 (0.59, 1.46)

0.72 (0.50, 1.05)

0.96 (0.50, 1.85)

0.62 (0.41, 0.94)

1.03 (0.63, 1.67)

0.75 (0.50, 1.14)

0.76 (0.44, 1.32)

0.79 (0.25, 2.47)

0.76 (0.52, 1.11)

0.76 (0.37, 1.59)

1.06 (0.32, 3.48)

0.70

0.65

0.26

0.46

0.12

1.00

0.87

No. of RFS events/

patients

HR

(95%CI)

p-

value

0.5 1.0 1.5 2.0

196/533

64/157

182/474

78/214

124/341

136/349

196/515

57/156

138/406

121/282

162/407

78/239

20/43

183/475

47/97

19/58

0.98 (0.74, 1.30)

0.87 (0.53, 1.43)

1.01 (0.75, 1.35)

0.80 (0.52, 1.26)

0.85 (0.59, 1.20)

1.02 (0.73, 1.43)

0.98 (0.74, 1.29)

0.85 (0.50, 1.43)

0.84 (0.60, 1.17)

1.09 (0.76, 1.56)

0.94 (0.69, 1.28)

1.04 (0.66, 1.63)

0.57 (0.24, 1.39)

0.90 (0.67, 1.20)

0.89 (0.49, 1.60)

1.13 (0.46, 2.79)

0.68

0.41

0.46

0.64

0.29

0.50

0.89

Tailored better Control better

Hazard

ratio

Tailored better Control better

22



• Conclusions

– In patients with completely resected NSCLC, using a tailored approach to select adjuvant chemotherapy did

not significantly improve survival although it was associated with an improved safety profile and a trend

towards improved efficacy


Grade 3–4 AEs occurring in ≥1%, n (%) Tailored arm Control arm

Neutropenia 45 (13.4) 64 (18.9)

Leukopenia 13 (3.9) 45 (13.3)

Nausea 13 (3.9) 15 (4.4)

Thrombocytopenia 11 (3.3) 26 (7.7)

Fatigue 9 (2.7) 5 (1.5)

Vomiting 7 (2.1) 6 (1.8)

Alopecia 7 (2.1) 0 (0)

Diarrhoea 5 (1.5) 1 (0.3)

Anaemia 3 (0.9) 9 (2.7)

Asthenia 1 (0.3) 5 (1.5)

23

PS01.05: Surgical and Clinical Outcomes With Neoadjuvant Atezolizumab in Resectable Stage IB–IIIB NSCLC: LCMC3 Trial Primary Analysis – Lee JM, et al

• Study objective

– To assess the surgical and clinical outcomes of neoadjuvant atezolizumab in patients with resectable stage

1B–IIIB NSCLC

Lee JM, et al. J Thorac Oncol 2021;16(suppl):Abstr PS01.05

Atezolizumab

1200 mg q3w

(2 cycles)


• Stage IB–IIIB resectable

NSCLC

• Treatment naïve

• ECOG PS 0–1

(n=181)

Primary endpoint

• MPR (≤10% viable tumour cells)

Secondary endpoints

• MPR by PD-L1 status, TMB, safety

Surgical

resection

Adjuvant

atezolizumab

1200 mg q3w

(12 months)

Clinical

benefit

24


• Key results

– Following atezolizumab, 66 (43%) patients were down-staged and 29 (19%) patients were up-staged


Downstaging, %

Pre-treatment cStage

(n=155)

Post-treatment cStage

(n=155)

ypT0N0M0 0 5

IA 0 11

IB 10 8

IIA 12 6

IIB 30 23

IIIA 39 27

IIIB 9 4

IV 0 1

n (%) n=159

Surgical approach Thoracotomy 73 (46)

Robotic 59 (37)

VATS 27 (17)

Extent of resection Lobectomy 125 (79)

Pneumonectomy 14 (9)

Bilobectomy 10 (6)

No resection 5 (3)

Wedge 3 (2)

Segmentectomy 2 (1)

Completeness of resection R0 145 (92)

R1 7 (4)

R2 7 (4)

25



• Conclusions

– In patients with resectable stage IB–IIIB NSCLC, neoadjuvant atezolizumab was generally well-tolerated and

resection was performed with low perioperative morbidity and mortality as well as with a high R0 rate


n=159

Intra-operative event, n (%)

Bronchial complications 1 (1)

Vascular complications 4 (3)

Median length of hospitalisation, days (range) 7.5 (2–68)

Deaths, n (%)

Before surgery 0

≤30 days after surgery1 (0.6)

[sudden death]

30–90 days after surgery1 (0.6)

[pneumonitis]

AEs, n (%)

TRAE irAEs

Pre-op

(n=181)

Post-op

(n=159)

Pre-op

(n=181)

Post-op

(n=159)

Grade 1 55 (30) 13 (8) 22 (12) 18 (11)

Grade 2 36 (20) 18 (11) 16 (9) 12 (8)

Grade 3 11 (6) 17 (11) 3 (2) 11 (7)

Grade 4 0 (0) 3 (2) 0 (0) 1 (1)

Grade 5 0 (0) 1 (1) 0 (0) 1 (1)

26

OA06.06: Clinical/Biomarker Data for Neoadjuvant Atezolizumab in Resectable Stage IB-IIIB NSCLC: Primary Analysis in the LCMC3 Study – Carbone DP, et al

• Study objective

– To assess the clinical and biomarker data of neoadjuvant atezolizumab in treatment naïve patients with

resectable stage 1B–IIIB NSCLC

Carbone DP, et al. J Thorac Oncol 2021;16(suppl):Abstr OA06.06

Atezolizumab

1200 mg q3w

(2 cycles)


• Stage IB–IIIB resectable

NSCLC


• ECOG PS 0–1

(n=181)

Primary endpoint

• MPR (≤10% viable tumour cells)

Secondary endpoints

• MPR by PD-L1 status, TMB, safety

Surgical

resection

Adjuvant

atezolizumab

1200 mg q3w

(12 months)

Clinical

benefit

27


• Key results

*Analysis population excluded EGFR and ALK positive patients; †calculated in the primary

efficacy population with TMB results; ‡local TPS score used if central score was not available Carbone DP, et al. J Thorac Oncol 2021;16(suppl):Abstr OA06.06

PD-L1 IHC at screening‡

p=0.30 p=0.089

TPS

<1%

TPS

≥1%

TPS

<50%

TPS

≥50%

Pathologic response

in the primary efficacy

population (n=144)

MPR rate*

(primary efficacy population

with known PD-L1 status, n=118)

<10 ≥10 <16 ≥16

TMB cut-off (mut/Mb)

MPR rate† by TMB cut-off

for all histologies (n=71)

MP

R,

%

50

40

30

20

10

0

MPR

pCR

21%

7%

10/144

13%

25%

7/53 16/65 8/73 15/45 8/51 6/20 9/59 5/12

30/14411%

33%

16%

30%

15%

42%p=0.162 p=0.004

28



• Conclusions

– In patients with resectable stage IB–IIIB NSCLC, neoadjuvant atezolizumab met the primary endpoint of

improvement in MPR rate and better pathologic responses were observed in those with high PD-L1

expression (TPS ≥50%) and higher TMB (≥16 mut/Mb)

Carbone DP, et al. J Thorac Oncol 2021;16(suppl):Abstr OA06.06

Events, n (%) 12-mo rate, % 18-mo rate, %

OS

Disease stage Stage I/II

Stage III

13 (18)

8 (11)

92

95

91

87

MPR No

Yes

17 (16)

2 (7)

92

96

87

92

DFS

MPR No

Yes

26 (24)

3 (10)

82

93

74

89

29

OA06.03: Patient-Reported Outcomes from ADAURA: Osimertinib as Adjuvant Therapy in Patients with Resected EGFR Mutated (EGFRm) NSCLC – Majem M, et al

• Study objective

– To assess the patient-reported outcomes of adjuvant osimertinib in patients with early stage EGFR-mutant

NSCLC

*Data previously reported Majem M, et al. J Thorac Oncol 2021;16(suppl):Abstr OA06.03

Primary endpoint

• DFS in stage II/IIIA patients

(investigator assessment)*

Secondary endpoints

• DFS in overall population*, OS, safety,

HRQoL (SF-36)

R

1:1

PD/3 years/

discontinuation

PD/3 years/

discontinuation

Stratification

• Stage (IB vs. II vs. IIIA)

• EGFRm (Ex19del vs. L858R)

• Race (Asian vs. non-Asian)


• Completely resected stage IB,

II, IIIA NSCLC

• Confirmed EGFR mutation

(Ex19del/L858R)

• With or without adjuvant

chemotherapy

• WHO PS 0–1

(n=682)

Placebo QD

(n=343)

Osimertinib 80 mg QD

(n=339)

30


• Key results

Majem M, et al. J Thorac Oncol 2021;16(suppl):Abstr OA06.03

PCS MCS

SF-36 component

Mixed model of repeated measures –

adjusted mean change from baseline (95%CI)

Definition of clinically meaningful change based

on the 3rd edition of the SF-36 scoring manual

Osimertinib Placebo Osimertinib - placebo

PCS 1.13 (0.54, 1.72) 2.31 (1.70, 2.91) -1.18 (-2.02, -0.34) ±2

MCS 1.34 (0.60, 2.08) 2.68 (1.92, 3.44) -1.34 (-2.40, -0.28) ±3

Me

an

(S

D)

ch

an

ge

fro

m b

ase

line

Osimertinib

Placebo20

10

0

-10

-20

9672482412Time, weeks

165212261274291

124172219275301

Osimertinib

Placebo

No. at risk

20

10

0

-10

-20

9672482412Time, weeks

165212261274291

124172219275301

Osimertinib

Placebo

No. at risk

31



• Conclusions

– In patients with resected EGFR-mutant NSCLC, there were no differences between adjuvant osimertinib and

placebo for changes from baseline to Week 96 or time to deterioration in HRQoL measures

*HR <1 favours osimertinib Majem M, et al. J Thorac Oncol 2021;16(suppl):Abstr OA06.03

Time to deterioration of

SF-36 health domains

Osimertinib

(n=339), n (%)

Placebo

(n=343), n (%) HR

Bodily pain 53 (15.6) 55 (16.0) 0.92

General health 68 (20.1) 58 (16.9) 1.15

Mental health 57 (16.8) 46 (13.4) 1.14

Physical functioning 52 (15.3) 42 (12.2) 1.18

Role-emotional 73 (21.5) 69 (20.1) 1.02

Role-physical 75 (22.1) 62 (18.1) 1.19

Social functioning 32 (9.4) 42 (12.2) 0.68

Vitality 47 (13.9) 37 (10.8) 1.18

Time to deterioration HR (95%CI)*

Physical component summary 1.17 (0.82, 1.67)

Mental component summary 0.98 (0.70, 1.39)

32

OA06.04: Postoperative Chemotherapy Use and Outcomes from ADAURA: Osimertinib as Adjuvant Therapy for Resected EGFR Mutated NSCLC – Wu Y, et al

• Study objective

– To assess postoperative chemotherapy use and outcomes of adjuvant osimertinib in patients with resected

EGFR-mutant NSCLC

Wu Y, et al. J Thorac Oncol 2021;16(suppl):Abstr OA06.04

Primary endpoint

• DFS in stage II/IIIA patients

(investigator assessment)*

Secondary endpoints

• DFS in overall population*, DFS at 2, 3, 4,

and 5 years, OS, safety, HRQoL

R

1:1

PD/3 years/

discontinuation

PD/3 years/

discontinuation

Stratification

• Stage (IB vs. II vs. IIIA)

• EGFRm (Ex19del vs. L858R)

• Race (Asian vs. non-Asian)


• Completely resected stage IB,

II, IIIA NSCLC

• Confirmed EGFR mutation

(Ex19del/L858R)

• With or without adjuvant

chemotherapy

• WHO PS 0–1

(n=682)

Placebo QD

(n=343)

Osimertinib 80 mg QD

(n=339)

*Data previously reported

33


• Key results


DFS in patients with adjuvant chemotherapy DFS in patients without adjuvant chemotherapy

Maturity 30%: Osimertinib 11%, placebo 50%

DFS events,

n (%)

Median DFS,

mo (95%CI) HR (95%CI)

Osimertinib (n=203) 22 (11) NR (38.8, NC) 0.16

(0.10, 0.26)Placebo (n=207) 103 (50) 22.1 (17.4, 32.9)

DF

S p

rob

ab

ility

1.0

0.8

0.6

0.4

0.2

0

Time from randomisation, months

4842363024181260

01144080121166190203

127244680119172207

No. at riskOsimertinib

Placebo

49%

89% 1.0

0.8

0.6

0.4

0.2

0

Time from randomisation, months

4842363024181260

0413345887106123136

111329426888115136

58%

89%

DFS events,

n (%)

Median DFS,

mo (95%CI) HR (95% CI)

Osimertinib (n=136) 15 (11) NR (NC, NC) 0.23

(0.13, 0.40)Placebo (n=136) 56 (41) 33.1 (22.6, NC)

Maturity 26%: Osimertinib 11%, placebo 41%

34



• Conclusions

– In patients with resected EGFR-mutant NSCLC, adjuvant osimertinib demonstrated improvement in DFS in

those with or without adjuvant chemotherapy and irrespective of disease stage


Stage DFS

With adjuvant chemotherapy Without adjuvant chemotherapy

Osimertinib (n=28) Placebo (n=30) Osimertinib (n=78) Placebo (n=76)

IB Events, n (%) 4 (14) 11 (37) 7 (9) 18 (24)

Median, months (95%CI) NR (33.0, NC) 48.2 (21.0, 48.2) NR (NC, NC) NR (NC, NC)

HR (95%CI) NC (NC, NC) 0.38 (0.15, 0.88)

II Events, n (%) 6 (7) 36 (42) 5 (14) 16 (48)

Median, months (95%CI) NR (NC, NC) 29.4 (22.1, NC) NR (27.7, NC) 22.1 (10.8, NC)

HR (95%CI) 0.15 (0.06, 0.32) 0.20 (0.07, 0.52)

IIIA Events, n (%) 12 (13) 56 (61) 3 (14) 22 (81)

Median, months (95%CI) 38.8 (34.3, NC) 12.9 (10.9, 19.4) 38.6 (38.6, NC) 11.2 (8.2, 21.9)

HR (95%CI) 0.13 (0.06, 0.23) 0.10 (0.02, 0.29)

Advanced NSCLCNot radically treatable stage III and stage IV

First line

36

PS01.07: Registrational Phase 2 Trial of Sotorasib in KRAS p.G12C Mutant NSCLC: First Disclosure of the Codebreak 100 Primary Analysis – Li BT, et al

• Study objective

– To assess the efficacy and safety of sotorasib, a KRAS G12C inhibitor, in patients with NSCLC harbouring a

KRAS p.G12C mutation

Li BT, et al et al. J Thorac Oncol 2021;16(suppl):Abstr PS01.07

Sotorasib 960 mg/day PO


• Locally advanced or metastatic NSCLC

• KRAS p.G12C mutation

• Progressed on prior standard therapies

(n=126)

Primary endpoint

• ORR (BICR, RECIST v1.1)

Secondary endpoints

• DoR, DCR, TTR, PFS, OS, safety

PD

37


• Key results


Progression-free survivalP

FS

1.0

0.8

0.6

0.4

0.2

0

Time, months

131211109876543210

0424313445495465757796119124No. at risk

mPFS: 6.8 months (95%CI 5.1, 8.2)

38



• Conclusions

– In patients with advanced NSCLC harbouring a KRAS p.G12C mutation, sotorasib demonstrated promising

activity and was generally well-tolerated


Grade 3 TRAEs, n (%) Sotorasib (n=126)

Any 25 (19.8)

Diarrhoea 5 (4.0)

ALT increased 6 (6.3)

AST increased 7 (5.6)

Blood alkaline phosphatase increased 1 (0.8)

Sotorasib (n=124)

ORR, % (95%CI) 37.1 (28.6, 46.2)

BOR, n (%)

CR 3 (2.4)

PR 43 (34.7)

SD 54 (43.5)

PD 20 (16.1)

NE/missing 4 (3.2)

DCR, % (95%CI) 80.6 (72.6, 87.2)

39Data cut-off: September 1, 2020. Median follow-up: 20.6 months

PS01.09: Pembrolizumab Plus Ipilimumab vs Pembrolizumab Plus Placebo as 1L Therapy for Metastatic NSCLC of PD-L1 TPS ≥50%: KEYNOTE-598 – Boyer M, et al

• Study objective

– To assess the efficacy and safety of pembrolizumab + ipilimumab as a 1L therapy for patients with metastatic

NSCLC with PD-L1 TPS ≥50%

Boyer M, et al. J Thorac Oncol 2021;16(suppl):Abstr PS01.09

Co-primary endpoints

• OS and PFS (BICR, RECIST v1.1)

Secondary endpoints

• ORR, DoR, safety

R

1:1

Stratification

• ECOG PS (0 vs. 1)

• Region (East Asia vs. not East Asia)

• Histology (squamous vs. nonsquamous)


• Stage IV NSCLC

• PD-L1 TPS ≥50%

• No EGFR mutations or ALK

translocations

• No prior systemic therapy

• ECOG PS 0–1

(n=568)

Pembrolizumab 200 mg q3w (up to 35 doses) +

placebo (up to 18 doses)

(n=284)

Pembrolizumab 200 mg q3w (up to 35 doses) +

ipilimumab 1 mg/kg q6w (up to 18 doses)

(n=284)

40


• Key results

*Nonbinding futility criteria met Boyer M, et al. J Thorac Oncol 2021;16(suppl):Abstr PS01.09

Events,

%

Median,

mo

(95%CI)

RMST at

24 mo,

mo

RMST at

max time,

mo

Pembro-Ipi 48.221.4

(16.6, NR)16.09 18.76

Pembro-Pbo 47.521.9

(18.0, NR)16.61 19.32

Overall survival

No. at risk Time, months

33302724211815129630

OS

, %

100

80

60

40

20

0

HR 1.08 (95%CI 0.85, 1.37); p=0.74

RMST difference at 24 mo: –0.52*

RMST difference at max observation time: –0.56*

12-month rate

63.6%

67.9%

00103762100146180204223245284Pembro-Ipi

02154177111154192215230252284Pembro-Pbo

41




Events, % Median, mo (95%CI)

Pembro-Ipi 66.2 8.2 (6.0, 10.5)

Pembro-Pbo 64.8 8.4 (6.3, 10.5)

Progression-free survival

No. at risk Time, months

33302724211815129630

PF

S, %

100

80

60

40

20

0

HR 1.06 (95%CI 0.86, 1.30); p=0.72

12-month rate

41.3%

42.1%

001919366599117146189284Pembro-Ipi

01411204375104124157198284Pembro-Pbo

42




Pembrolizumab + ipilimumab

(n=284)

Pembrolizumab + placebo

(n=284)

ORR, % (95%CI) 45.4 (39.5, 51.4) 45.4 (39.5, 51.4)

BOR, n (%)

CR 13 (4.6) 8 (2.8)

PR 116 (40.8) 121 (42.6)

SD 70 (24.6) 73 (25.7)

PD 51 (18.0) 44 (15.5)

NE 6 (2.1) 6 (2.1)

NA 28 (9.9) 32 (11.3)

Median DoR, mo (range) 16.1 (1.1+ to 26.0) 17.3 (2.0+ to 29.4+)

12-mo DoR rate, % 60.9 65.8

43



• Conclusions

– In patients with metastatic NSCLC and PD-L1 TPS ≥50% with no EGFR or ALK aberrations, 1L

pembrolizumab + ipilimumab did not improve outcomes after a median follow-up of 20.6 months and had a

higher rate of toxicity than with pembrolizumab alone


AEs, n (%)

TRAEs irAEs

Pembrolizumab +

ipilimumab (n=282)

Pembrolizumab +

placebo (n=281)

Pembrolizumab +

ipilimumab (n=282)

Pembrolizumab +

placebo (n=281)

Any grade 215 (76.2) 192 (68.3) 126 (44.7) 91 (32.4)

Grade 3–5 99 (35.1) 55 (19.6) 57 (20.2) 22 (7.8)

Serious 78 (27.7) 39 (13.9) 54 (19.1) 20 (7.1)

Led to death 7 (2.5) 0 (0) 6 (2.1) 0 (0)

Led to discontinuation

Ipilimumab or placebo 17 (6.0) 9 (3.2) 5 (1.8) 3 (1.1)

Both drugs 54 (19.1) 21 (7.5) 34 (12.1) 12 (4.3)

44

OA01.03: Clinical Benefits of First-Line (1L) Cemiplimab Monotherapy by PD-L1 Expression Levels in Patients With Advanced NSCLC – Kilickap S, et al

• Study objective

– To assess the efficacy and safety of cemiplimab, a PD-1 inhibitor, as a 1L therapy for patients with

advanced NSCLC and PD-L1 expression of ≥50% in the EMPOWER-Lung 1 study

*Optional continuation of cemiplimab + chemotherapy (4 cycles); †optional crossover to cemiplimab monotherapy Kilickap S, et al. J Thorac Oncol 2021;16(suppl):Abstr OA01.03

Post-hoc analysis

• Clinical benefit by PD-L1 expression

(≥90%, >60% to <90% and ≥50% to ≤60%)

Cemiplimab 350 mg IV q3w*

(n=238)Key patient inclusion criteria

• Advanced NSCLC

• PD-L1 ≥50%

• No EGFR, ALK or ROS1 mutations


• ECOG PS 0–1

(n=710)

Chemotherapy investigator choice†

(4–6 cycles)

(n=237)

R

1:1

Stratification

• Histology (squamous vs. nonsquamous)

• Region (Europe, Asia or RoW)

PD

PD

45


• Key results

Kilickap S, et al. J Thorac Oncol 2021;16(suppl):Abstr OA01.03

Overall survival

Pro

babili

ty o

f O

S

1.0

0.8

0.6

0.4

0.2

0

Time, months

181614121086420

Cemiplimab

PD-L1 ≥90%

PD-L1 >60 to <90%

PD-L1 ≥50 to ≤60%

Chemotherapy

PD-L1 ≥90%

PD-L1 >60 to <90%

PD-L1 ≥50 to ≤60%

mOS, months (95%CI)

HR (95%CI)

Cemiplimab

(n=238)

Chemotherapy

(n=237)

≥90% NR (13.4, NE) 13.3 (10.2, NE) 0.54 (0.27, 1.10)

>60 to <90% NR (NE, NE) 14.2 (9.6, 17.5) 0.49 (0.26, 0.92)

≥50 to ≤60% NR (13.2, NE) 11.7 (8.3, NE) 0.74 (0.44, 1.24)

mPFS, months (95%CI)

HR (95%CI)

Cemiplimab

(n=238)

Chemotherapy

(n=237)

≥90% 12.7 (9.8, 13.4) 6.1 (4.2, 6.2) 0.33 (0.19, 0.58)

>60 to <90% 6.2 (4.2, 8.4) 4.3 (4.1, 5.9) 0.57 (0.38, 0.85)

≥50 to ≤60% 4.3 (2.8, 5.2) 6.0 (4.4, 6.2) 0.89 (0.61, 1.29)


Pro

babili

ty o

f P

FS

1.0

0.8

0.6

0.4

0.2

0

Time, months

181614121086420

46



• Conclusions

– In patients with advanced NSCLC and PD-L1 expression, cemiplimab demonstrated greater improvements in

survival and larger reductions in tumour volume in those with higher PD-L1 expression levels

Kilickap S, et al. J Thorac Oncol 2021;16(suppl):Abstr OA01.03

PD-L1 expression

tertile

ORR, % (95%CI)

Cemiplimab Chemotherapy

Overall ≥50% 35.3 (29.2, 41.7) 17.7 (13.1, 23.2)

≥50% to ≤60% 28.0 (18.7, 39.1) 21.4 (13.2, 31.7)

>60% to <90% 39.5 (28.4, 51.4) 16.7 (8.9, 27.3)

≥90% 38.8 (28.1, 50.3) 14.8 (7.9, 24.4)

Grade 3–5 TEAEs

occurring in ≥5%, n (%)

Cemiplimab

(n=355)

Chemotherapy

(n=342)

Any 132 (37.2) 166 (48.5)

Anaemia 12 (3.4) 56 (16.4)

Pneumonia 17 (4.8) 19 (5.6)

Thrombocytopenia 0 (0) 28 (8.2)

Neutropenia 2 (0.6) 35 (10.2)

Decreased neutrophil count 1 (0.3) 18 (5.3)

47

OA02.03: Pembrolizumab Plus Platinum Chemotherapy and Radiotherapy in Unresectable, Locally Advanced, Stage III NSCLC: KEYNOTE-799 – Reck M, et al

• Study objective

– To assess the efficacy and safety of pembrolizumab + concurrent chemoradiation therapy in patients with

locally advanced stage III NSCLC

*60 Gy in 30 daily 2-Gy fractions Reck M, et al. J Thorac Oncol 2021;16(suppl):Abstr OA02.03

Primary endpoints


• Proportion developing grade ≥3 pneumonitis

Secondary endpoints

• PFS, OS, safety


• Stage IIIA-C, unresectable,

locally advanced NSCLC


• ECOG PS 0–1

(n=216)

Pembrolizumab 200 mg +

pemetrexed 500 mg/m2 +

cisplatin 75 mg/m2 q3w


paclitaxel 200 mg/m2 +

carboplatin AUC6 q3w

Cohort A: Squamous and nonsquamous NSCLC (n=112)

Cohort B: Nonsquamous NSCLC (n=101)


pemetrexed 500 mg/m2 +

cisplatin 75 mg/m2 q3w +

thoracic radiotherapy*


paclitaxel 45 mg/m2 +

carboplatin AUC2 q3w +

thoracic radiotherapy*

Pembrolizumab

200 mg q3w

Pembrolizumab

200 mg q3w

Cycle 1 Cycle 2–3 Cycle 4–17

48


• Key results

Reck M, et al. J Thorac Oncol 2021;16(suppl):Abstr OA02.03

Progression-free

survival

Overall

survival

Cohort A: Squamous and nonsquamous NSCLC

Time, months211815129630

PF

S,

%

100

80

60

40

20

0

n

112

Median (95%CI)

NR (16.6, NR)

12-month rate

67.7%

023053688193112No. at risk

Cohort B: Nonsquamous only

Time, months

PF

S,

%

100

80

60

40

20

0

n

61

Median (95%CI)

NR (10.6, NR)

12-month rate

65.2%

1815129630

092037445261No. at risk

Time, months211815129630

OS

, %

100

80

60

40

20

0

n

112

Median (95%CI)

NR (NR, NR)

12-month rate

81.2%

0850839498106112No. at riskTime, months

211815129630

OS

, %

100

80

60

40

20

0

n

61

Median (95%CI)

NR (NR, NR)

12-month rate

88.0%

06153756596161No. at risk

49



• Conclusions

– In patients with unresectable, locally advanced stage III NSCLC, adding pembrolizumab to concurrent

chemoradiation continued to demonstrate encouraging antitumor activity and the safety profile was

consistent with those of the established profiles


Cohort A (n=112) Cohort B (n=61)

ORR, n (%) [95%CI] 78 (69.6) [60.2, 78.0] 43 (70.5) [57.4, 81.5]

BOR, n (%)

CR 4 (3.6) 3 (4.9)

PR 74 (66.1) 40 (65.6)

SD 21 (18.8) 12 (19.7)

PD 1 (0.9) 0 (0)

NE 2 (1.8) 0 (0)

NA 10 (8.9) 6 (9.8)

Median DoR, mo (range) NR (1.4+ to 16.1+) NR (2.0+ to 15.9+)

AEs Cohort A (n=112) Cohort B (n=61)

Grade ≥3 pneumonitis, n (%) [95%CI] 9 (8.0) [3.7, 14.7] 8 (7.9) [3.5, 15.0]

TRAE, n (%) 105 (93.8) 96 (95.0)

Grade 3–5 72 (64.3) 47 (46.5)

Led to death 4 (3.6) 1 (1.0)

Led to discontinuation of any component 38 (33.9) 16 (15.8)

Pembrolizumab 27 (24.1) 15 (14.9)

Radiotherapy 2 (1.8) 0 (0)

Chemotherapy 18 (16.1) 3 (3.0)

Immune-mediated & infusion reactions 59 (52.7) 36 (35.6)

Grade 3–5 18 (16.1) 10 (9.9)

Led to death 4 (3.6) 1 (1.0)

50

OA07.09: Sintilimab in Combination with Anlotinib as First-Line Therapy for Advanced NSCLC: Final Analysis of Primary Endpoints – Han B, et al

• Study objective

– To assess the efficacy and safety of sintilimab, a PD-1 inhibitor, + anlotinib, an anti-angiogenesis multikinase

inhibitor, as a 1L therapy for patients with advanced NSCLC

Han B, et al. J Thorac Oncol 2021;16(suppl):Abstr OA07.09

Sintilimab 200 mg IV D1 +

anlotinib 12 mg PO D1–14 q3w


• Stage IIIB–IV NSCLC

• No driver gene (EGFR, ALK, ROS1)


• ECOG PS 0–1

(n=22)

Primary endpoints

• ORR, safety

Secondary endpoints

• DCR, PFS, OS

PD/toxicity

51


• Key results

Median follow-up: 15.8 months (range 8.3–19.3)

Data cut-off: April 30, 2020 Han B, et al. J Thorac Oncol 2021;16(suppl):Abstr OA07.09


Su

rviv

al p

rob

ab

ility

, %

100

75

50

25

0

181614121086420

0 (13)1 (12)4 (10)9 (7)15 (1)16 (1)19 (1)21 (1)22 (0)22 (0)

Time, months

Sintilimab

Patient subgroups

mPFS,

mo (95%CI)

12-mo PFS,

% (95%CI)

ITT (n=22) 15 (8.3, NR) 71.4 (47.2, 86.0)

Nonsquamous (n=9) NR (4.3, NR) 66.7 (28.2, 87.8)

Squamous (n=12) 13 (7.7, NR) 72.7 (37.1, 90.3)

PD-L1+ (n=13) NR (7.7, NR) 76.9 (44.2, 91.9)

PD-L1– (n=8) 14 (4.5, 15) 62.5 (22.9, 86.1)

TMB ≥10 (n=6) NR (NR, NR) 100 (100, 100)

TMB <10 (n=10) 14 (4.3, 15) 60.0 (25.3, 82.7)

No. at risk (no. censored)

52



• Conclusions

– In patients with advanced NSCLC, 1L sintilimab + anlotinib demonstrated encouraging activity and was

generally well-tolerated

Han B, et al. J Thorac Oncol 2021;16(suppl):Abstr OA07.09

Response and duration n=22

ORR, % (95%CI) 72.7 (49.8, 89.3)

BOR, n (%)

CR 0 (0)

PR 16 (72.7)

SD 6 (27.3)

DCR, % (95%CI) 100 (84.6, 100)

Median TTR, mo (95%CI) 1.6 (1.4, 2.9)

Median DoR, mo (95%CI) NR (3.2, NC)

AE, n (%) n=22

Any TRAE 22 (100)

Grade ≥3 TRAEs 12 (54.4)

Grade ≥3 irAEs 1 (4.5)

Led to anlotinib dose reduction 5 (22.7)

Led to discontinuation

Both drugs 1 (4.5)

Sintilimab 1 (4.5)

Anlotinib 1 (4.5)

Grade 3 TRAE, n (%) n=22

Hypertension 2 (9.1)

Rash 1 (4.5)

Hand-foot skin reaction 1 (4.5)

53

MA11.05: Tepotinib in Patients with MET exon 14 (METex14) Skipping Advanced NSCLC: Updated Efficacy Results from VISION Cohort A – Paik PK, et al

• Study objective

– To assess the updated efficacy and safety of tepotinib in patients with advanced NSCLC and MET exon 14

skipping mutation who had at least 9 months of follow-up

Paik PK, et al. J Thorac Oncol 2021;16(suppl):Abstr MA11.05

Tepotinib 500 mg/day PO

(n=152)


• Advanced NSCLC

• MET exon 14 skipping mutation

• EGFR or ALK WT

(n=255)

Primary endpoint

• ORR (RECIST v1.1)

Secondary endpoints

• DoR, safety

54


• Key results

Data cut-off: July 1, 2020 Paik PK, et al. J Thorac Oncol 2021;16(suppl):Abstr MA11.05

Efficacy

according to

IRC

Treatment-

naïve

(n=69)

Previously

treated

(n=83)

Overall

(N=152)

ORR, %

(95%CI)

44.9

(32.9, 57.4)

44.6

(33.7, 55.9)

44.7

(36.7, 53.0)

BOR, n (%)

CR 0 0 0

PR 31 (44.9) 37 (44.6) 68 (44.7)

SD 16 (23.2) 23 (27.7) 39 (25.7)

PD 13 (18.8) 13 (15.7) 26 (17.1)

NE 9 (13.0) 10 (12.0) 19 (12.5)

Median DoR, mo

(95%CI)

10.8

(6.9, NE)

11.1

(9.5, 18.5)

11.1

(8.4, 18.5)

Median PFS, mo

(95%CI)

8.5

(6.8, 11.3)

10.9

(8.2, 12.7)

8.9

(8.2, 11.2)

N ORR (95%CI) by IRC

Overall

Treatment-naïve

Previously treated

Platinum-based CT

Also received IO

As combination

As single agent in

a separate line

152

69

83

74

29

10

20

44.7 (36.7, 53.0)

44.9 (32.9, 57.4)

44.6 (33.7, 55.9)

48.6 (36.9, 60.6)

41.4 (23.5, 61.1)

40.0 (12.2, 73.8)

40.0 (19.1, 63.9)

0 20 40 60 80 100

ORR, % and 95%CI

55



• Conclusions

– In patients with advanced NSCLC and MET exon 14 skipping mutations, tepotinib demonstrated encouraging

activity across all therapy lines and had a manageable safety profile

Paik PK, et al. J Thorac Oncol 2021;16(suppl):Abstr MA11.05

TRAEs, n (%)

Treatment-

naïve

(n=125)

Previously

treated

(n=130)

Prior IO

(n=66)

Overall

(N=255)

Any 109 (87) 111 (85) 55 (83) 220 (86)

Grade ≥3 39 (31) 25 (19) 12 (18) 64 (25)

Led to dose reduction 39 (31) 32 (25) 15 (23) 71 (28)

Led to interruption 50 (40) 40 (31) 22 (33) 90 (35)

Led to discontinuation 19 (15) 8 (6) 5 (8) 27 (11)

TRAEs occurring in ≥10%

of all patients, n (%)

Treatment-

naïve

(n=125)

Previously

treated

(n=130)

Prior IO

(n=66)

Overall

(N=255)

Peripheral oedema 73 (58) 65 (50) 30 (45) 138 (54)

Nausea 30 (24) 21 (16) 8 (12) 51 (20)

Diarrhoea 26 (21) 24 (18) 9 (14) 50 (20)

Blood creatinine increased 23 (18) 22 (17) 13 (20) 45 (18)

Hypoalbuminemia 21 (17) 16 (12) 9 (14) 37 (15)

Advanced NSCLCNot radically treatable stage III and stage IV

Later lines

57

OA01.06: Randomised Phase 2 Study of Nivolumab (N) Versus Nivolumab and Ipilimumab (NI) Combination in EGFR Mutant NSCLC – Lai GG, et al

• Study objective

– To assess the efficacy and safety of nivolumab with or without ipilimumab in patients with EGFR-mutant

NSCLC

*Enrolment was terminated early due to futility Lai GG, et al. J Thorac Oncol 2021;16(suppl):Abstr OA01.06

Primary endpoint

• ORR

Secondary endpoint

• Safety

R

1:1

Crossover

permitted

Stratification

• PD-L1 status

• Presence of brain metastasis


• Advanced NSCLC

• EGFR mutant

• Failed 1 line of standard EGFR TKI

(n=31*)Nivolumab

(n=15)

Nivolumab + ipilimumab

(n=16)

58


• Key results

Lai GG, et al. J Thorac Oncol 2021;16(suppl):Abstr OA01.06

Progression-free survivalBest overall response

-30

-10

10

30

50

70

90

110

130

150

Nivo + Ipi

Nivo

Nivo + Ipi, n (%) Nivo, n (%) Total (%)

PR 1 (6.3) 0 (0) 1 (8.2)

SD 6 (37.5) 6 (40.0) 12 (38.7)

PD 9 (56.8) 8 (53.3) 17 (54.8)

*1 not evaluable†Clinical PD

* †

% c

ha

ng

e in

tu

mo

ur

siz

e r

ela

tive

to

ba

se

line

9 23 6 27 21 26 3 20 8 30 11 29 19 12 2817 31 13 25 1 4 18 14 10 15 24 16 2 5 7Patient number

121086420

Su

rviv

al p

rob

ab

ility

1.00

0.75

0.50

0.25

0

Time from start of treatment, monthsNo. at risk

01112515

02223516

Nivo

Nivo + Ipi

mPFS,

mo (95%CI)

6-mo PFS rate,

% (95%CI)

Nivo + Ipi 1.22 (1.15, NE) 8.9 (1.5, 54.4)

Nivo 1.31 (1.22, NE) 8.3 (1.3, 52.6)

Overall 1.31 (1.15, 2.53) 9.0 (2.5, 31.8)

p=0.87

59



• Conclusions

– In patients with pretreated EGFR-mutant NSCLC, neither nivolumab alone nor nivolumab + ipilimumab

demonstrated any significant clinical benefit

Lai GG, et al. J Thorac Oncol 2021;16(suppl):Abstr OA01.06

AEs, n (%) Any grade Grade 3

Any 23 (74.2) 2 (6.0)

Immune-related

Skin 11 (35.5) -

Endocrine 4 (12.9) 1 (3.2)

Gastrointestinal 3 (9.6) -

Hepatic 3 (9.6) -

Pulmonary 1 (3.2) -

Musculoskeletal - 1 (3.2)

60

OA01.07: A Phase II Study of the Oral Selective AXL Inhibitor Bemcentinib with Pembrolizumab in Patients with Advanced NSCLC – Krebs MG, et al

• Study objective

– To assess the efficacy and safety of bemcentinib, an AXL inhibitor, + pembrolizumab in patients with

advanced NSCLC

Krebs MG, et al. J Thorac Oncol 2021;16(suppl):Abstr OA01.07

Primary endpoint


Secondary endpoints

• DCR, PFS, OS, safety

Cohort C: Post-chemo-CPI (n=29)

Progressing on platinum-doublet chemotherapy

+ pembrolizumab

Cohort B: Post-CPI (n=29)

Progressing on prior CPI

Cohort A: Post-chemo (n=48)

Failed chemotherapy, IO naive


• Stage IV lung adenocarcinoma

• Previously treated

(n=106)

Bemcentinib 200 mg/day

+ pembrolizumab 200 mg

q3w

61


• Key results

Krebs MG, et al. J Thorac Oncol 2021;16(suppl):Abstr OA01.07

Cohort BCohort A

cAXL+ve (n=7) cAXL-ve (n=7)

mPFS, mo 4.73 1.87

HR (95%CI); p-value 0.22 (0.04, 1.26); 0.066

ORR, n (%) 1 (14) 6 (86)

CBR, n (%) 0 (0) 2 (29)

cAXL+ve (n=15) cAXL-ve (n=15)

mPFS, mo 8.4 1.9

mOS, mo 17.3 12.4

ORR, n (%) 5 (33) 11 (73)

CBR, n (%) 1 (7) 6 (40)

PF

S p

rob

ab

ility

1.00

0.75

0.50

0.25

0

Time, months24211815129630

Median:

8.4 mo

Median:

1.9 mop=0.031

PF

S p

robabili

ty

1.00

0.75

0.50

0.25

0

Time, months

Median:

4.73 moMedian:

1.87 mo

p=0.031

109876543210

HR 0.22 (95%CI 0.04, 1.26)

p=0.066cAXL positive

cAXL negative cAXL positive

cAXL negative

62



• Conclusions

– In pretreated patients with advanced NSCLC who were cAXL+, bemcentinib + pembrolizumab demonstrated

clinical activity and was generally well-tolerated

– Results for progression after chemo-immunotherapy are expectedKrebs MG, et al. J Thorac Oncol 2021;16(suppl):Abstr OA01.07

TRAEs occurring in ≥10% (n=75), n (%) Any grade Grade ≥3

ALT increased 25 (33) 9 (12)

AST increased 24 (32) 6 (8)

Diarrhoea 24 (32) 1 (1)

Asthenia 14 (19) 4 (5)

Pruritus 12 (16) 0 (0)

Nausea 11 (15) 0 (0)

Blood creatinine increased 10 (13) 0 (0)

ECG QT prolonged 10 (13) 1 (1)

Fatigue 10 (13) 1 (1)

Anaemia 9 (12) 2 (3)

Appetite decreased 8 (11) 0 (0)

63

OA03.03: Datopotamab Deruxtecan (Dato-DXd; DS-1062), a TROP2 ADC, in Patients With Advanced NSCLC: Updated Results of TROPION-PanTumor01 Phase 1 Study – Spira AI, et al

• Study objective

– To assess the efficacy and safety of datopotamab deruxtecan, a TROP2 ADC, in patients with advanced or

metastatic NSCLC

Spira AI, et al. J Thorac Oncol 2021;16(suppl):Abstr OA03.03

Primary endpoints

• MTD, safety

Secondary endpoints

• Efficacy, PK

Datopotamab deruxtecan 4 mg/kg

(n=50)


(n=45)


(n=80)Key patient inclusion criteria

• Advanced or metastatic NSCLC

• Refractory to or relapsed on

standard treatment

• Tumour tissue available

(n=175)

64


• Key results

– mPFS (95%CI): 4 mg/kg: 4.3 mo (2.0, NE); 6 mg/kg: 8.2 mo (1.5, 11.8); 8 mg/kg: 5.4 mo (4.1, 7.1)


Best change in sum of diameters and overall response (BICR)

Best perc

ent

change in

SoD

from

baselin

e, %

80

60

40

20

0

–20

–40

–60

–80

–100

Dato-DXd

dose

Response-

evaluable

patients, n

Confirmed

CR/PR, n

CR/PR (too

early to be

confirmed), n

ORR,

n (%)

DCR,

n (%)

PD,

n (%)

4 mg/kg 40 7 2 9 (23) 29 (73) 6 (15)

6 mg/kg 39 6 2 9 (21) 26 (67) 8 (21)

8 mg/kg 80 19 1 20 (25) 64 (80) 7 (9)

Dato-DXd dose

4 mg/kg

6 mg/kg

8 mg/kg

65



• Conclusions

– In heavily pretreated patients with advanced NSCLC, datopotamab deruxtecan provided promising antitumor

activity with a manageable safety profile


AEs, n (%) Dato-DXd 8 mg/kg (n=80) Dato-DXd 6 mg/kg (n=80) Dato-DXd 4 mg/kg (n=80)

TEAE 79 (99) 41 (91) 48 (96)

Grade ≥3 45 (56) 17 (38) 11 (22)

TRAE 76 (95) 35 (78) 43 (86)

Grade ≥3 27 (34) 7 (16) 5 (10)

Serious TEAE 38 (48) 16 (36) 9 (18)

Treatment related 16 (20) 4 (9) 4 (8)

TEAE led to death 7 (9) 1 (2) 4 (8)

Treatment related 2 (3) 0 (0) 1 (2)

66

OA03.04: Efficacy and Safety of the Novel HER3 Directed Antibody Drug Conjugate Patritumab Deruxtecan (HER3-DXd; U3-1402) in EGFR-mutated NSCLC – Yu H, et al

• Study objective

– To assess the safety and activity of patritumab deruxtecan, a novel HER3-directed ADC, in pretreated

patients with advanced T790M– EGFR-mutant NSCLC

Yu H, et al. J Thorac Oncol 2021;16(suppl):Abstr OA03.04

Primary endpoint

• ORR (BICR)

Secondary endpoint

• Safety

Patritumab deruxtecan

5.6 mg/kg q3w

(n=12)


• Metastatic/unresectable NSCLC

• EGFR mutation

• Progression on osimertinib or

after progression on erlotinib,

gefitinib or afatinib in T790M–

(n=57)

Dose escalation

(3.2 mg/kg–6.4 mg/kg)

Dose expansion

Cohort 1

Patritumab deruxtecan

5.6 mg/kg q3w

Adenocarcinoma and

treated ≥EGFR TKI

and ≥prior platinum

(n=45)

67


• Key results


Activity according to BICR evaluation

(efficacy-evaluable population)

1514131211109876543210

Treatment duration, months

CR

PR

SD

PD

Treatment ongoing (27 of 56 patients [48%])

Treatment ongoing after progression

Confirmed BOR, n (%) n=56

Confirmed ORR, n (%) [95%CI] 14 (25) [14.4, 38.4]

Confirmed BOR, n (%)

CR 1 (2)

PR 13 (23)

SD 25 (45)

PD 9 (16)

NE 8 (14)

DCR, n (%) [95%CI] 39 (70) [55.9, 81.2]

Median TTR, months (range) 2.0 (1.2–2.8)

Median DoR, months (range) 6.9 (3.0–7.0)

68



• Conclusions

– In heavily pretreated patients with T790M– EGFR-mutant NSCLC, patritumab deruxtecan demonstrated

early promising antitumor activity and had a manageable safety profile


TEAEs occurring in ≥20% of patients (n=57), n (%) Any grade Grade ≥3

Fatigue 33 (58) 5 (9)

Nausea 31 (54) 2 (4)

Thrombocytopenia 30 (53) 16 (28)

Appetite decreased 20 (35) 1 (2)

Neutropenia 19 (33) 11 (19)

Vomiting 17 (30) 1 (2)

Alopecia 17 (30) -

Anaemia 15 (26) 5 (9)

Constipation 14 (25) 0 (0)

AEs, n (%) n=57

TEAE 57 (100)

Grade ≥3 38 (67)

Led to discontinuation 5 (9)

Led to dose reduction 10 (18)

Led to dose interruption 17 (30)

Led to death 3 (5)

Serious TEAE 21 (37)

Grade ≥3 18 (32)

Treatment related 11 (19)

69

OA04.03: Mobocertinib in NSCLC With EGFR Exon 20 Insertions: Results From EXCLAIM and Pooled Platinum-Pretreated Patient Populations – Zhou C, et al

• Study objective

– To assess the efficacy and safety of mobocertinib, a TKI targeting EGFR exon 20 in-frame insertion

mutations, in patients with NSCLC and EGFR exon 20 insertions

Zhou C, et al. J Thorac Oncol 2021;16(suppl):Abstr OA04.03

Primary endpoint

• ORR (ICR, RECIST v1.1)

Secondary endpoints

• TTR, DCR, DoR, PFS, safety

Mobocertinib

(n=28; 22 prior platinum)


• Locally advanced or metastatic

NSCLC

• EGFR exon20 insertion

mutation

• ≥1 prior line of therapy

• ECOG PS 0–1

Dose escalation/expansion

Mobocertinib 160 mg/day PO

(n=96; 86 prior platinum)

EXCLAIM Extension cohort

70


• Key results


Platinum-pretreated cohort (n=114) EXCLAIM cohort (n=96)

Pro

babili

ty o

f P

FS

1.0

0.8

0.6

0.4

0.2

0

242220181614121086420

02455681118426484114

Time, months

Pro

babili

ty o

f P

FS

1.0

0.8

0.6

0.4

0.2

0

121086420

131033537196

Time, months

Censored

Number of events: 44

Median: 7.3

Min, Max: 0.0, 12.0

Number of events: 56

Median: 7.3

Min, Max: 0.0, 24.0

Censored


No. at risk

71



• Conclusions

– In patients with NSCLC and EGFR exon 20 insertions, mobocertinib demonstrated clinical activity with a RR

of 23% in the EXCLAIM extension cohort


Platinum-pretreated

cohort (n=114)

EXCLAIM cohort

(n=96)

Median time on treatment, mo (range) 7.0 (0–31) 6.5 (0–14)

ORR per IRC, n (%) [95%CI] 30 (26) [19, 35] 22 (23) [15, 33]

ORR per investigator, n (%) [95%CI] 40 (35) [26, 45] 31 (32) [23, 43]

DoR per IRC, mo (95%CI) 17.5 (8.3, NE) NE (8.3, NE)

DoR per investigator, mo (95%CI) 13.9 (5.6, NE) NE (5.5, NE)

DCR per IRC, n (%) [95%CI] 89 (78) [69, 85] 73 (76) [66, 84]

DCR per investigator, n (%) [95%CI] 89 (78) [69, 85] 72 (75) [65, 83]

AEs, n (%)

Platinum-pretreated

cohort (n=114)

EXCLAIM cohort

(n=96)

Any TRAE 113 (99) 95 (99)

Grade ≥3 TRAE 53 (46) 39 (41)

Serious TEAE 52 (46) 39 (41)

AE led to dose reduction 28 (25) 20 (21)

AE led to treatment discontinuation 19 (17) 10 (10)

TRAE led to death 1 (1) 1 (1)

72

OA04.04: Amivantamab in Post-platinum EGFR Exon 20 Insertion Mutant Non-small Cell Lung Cancer – Sabari JK, et al

• Study objective

– To assess the efficacy and safety of amivantamab, an EGFR-MET bispecific antibody, in a cohort of patients

with NSCLC and EGFR exon 20 insertion mutation who had progressed on prior platinum-based

chemotherapy in the CHRYSALIS study

*1400 mg for ≥80 kg Sabari JK, et al. J Thorac Oncol 2021;16(suppl):Abstr OA04.04

Primary endpoint

• ORR (investigator assessed, RECIST v1.1)

Secondary endpoints

• CBR, DoR, PFS, OS, safety

Amivantamab 1050 mg*

(n=81)


• Unresectable or metastatic NSCLC

• EGFR exon 20 insertion mutation

• Progressed on platinum-based

chemotherapy

(n=114)

73


• Key results

Sabari JK, et al. J Thorac Oncol 2021;16(suppl):Abstr OA04.04

Best overall responseAmivantamab: Efficacy by BICR

BICR-assessed response Efficacy population (n=81)

ORR, % (95%CI) 40 (29, 51)

BOR, n (%)

CR 3 (4)

PR 29 (36)

SD 39 (48)

PD 8 (10)

NE 1 (1)

Median DoR, mo (95%CI) 11.1 (6.9, NR)

CBR, % (95%CI) 74 (63, 83)

mPFS, mo (95%CI) 8.3 (6.5, 10.9)

mOS, mo (95%CI) 22.8 (14.6, NR)

Median follow-up: 9.7 mo (range 1.1–29.3)

Overall

Age, years

<65 years

≥65 years

Sex

Male

Female

Race

Asian

Non-Asian

Baseline ECOG PS

0

≥1

Prior lines of therapy

1

2

≥3

History of smoking

Yes

No

History of brain metastases

Yes

No

n/N ORR, % (95%CI)ORR, %

32/81

21/48

11/33

15/33

17/48

17/40

14/32

14/26

18/55

10/31

7/24

15/26

13/38

19/43

7/18

25/63

40 (29, 51)

44 (30, 59)

33 (18, 52)

46 (28, 64)

35 (22, 51)

43 (27, 59)

44 (26, 62)

54 (33, 73)

33 (21, 47)

32 (17, 51)

29 (13, 51)

58 (37, 77)

34 (20, 51)

44 (29, 60)

39 (17, 64)

40 (28, 53)

100806040200

74



• Conclusions

– In previously platinum-treated patients with NSCLC and EGFR exon 20 insertion mutation, amivantamab

demonstrated encouraging activity and was generally well-tolerated

Sabari JK, et al. J Thorac Oncol 2021;16(suppl):Abstr OA04.04

BOR by insertion region ORR, % CBR, %

Helical (n=1) 100 100

Near loop (n=54) 41 70

Far loop (n=8) 25 75

Not detected by ctDNA (n=18) 39 83

TRAEs, n (%) Safety population (n=114)

Any 112 (98)

Grade ≥3 18 (16)

Serious 10 (9)

Led to discontinuation 5 (4)

Led to dose reduction 15 (13)

Led to dose interruption 24 (21)

75

OA04.05: Trastuzumab Deruxtecan in HER2-Overexpressing Metastatic Non-Small Cell Lung Cancer: Interim Results of DESTINY-Lung01 – Nakagawa K, et al

• Study objective

– To assess the efficacy and safety of trastuzumab deruxtecan (T-DXd) in patients with HER2-overexpressing

metastatic NSCLC

*Data previously presented at ASCO 2020 Nakagawa K, et al. J Thorac Oncol 2021;16(suppl):Abstr OA04.05

Primary endpoint

• ORR (ICR)

Secondary endpoints

• DCR, DoR, PFS, OS, safety

Cohort 1:

HER2 expressing (IHC3+ or IHC2+)

T-Dxd 6.4 mg/kg q3w

(n=49)


• Unresectable/metastatic

nonsquamous NSCLC

• Relapsed/refectory to standard

treatment

• HER2 expressing or HER2-

activating mutation

• No prior HER2-targeted therapy

Cohort 2*:

HER2 mutated

T-Dxd 6.4 mg/kg q3w

(n=42)

76


• Key results

Nakagawa K, et al. J Thorac Oncol 2021;16(suppl):Abstr OA04.05

PFS (n=49) OS (n=49)

mPFS 5.4 mo (95%CI 2.8, 7.0) mOS 11.3 mo (95%CI 7.8 NE)

Time, months

PF

S p

robabili

ty

1.0

0.8

0.6

0.4

0.2

0

131211109876543210

022235710172326294549No. at risk

Upper & lower 95%CI

Censored

Time, months

OS

pro

babili

ty

1.0

0.8

0.6

0.4

0.2

0

Upper & lower 95%CI

Censored

131211109876543210 191817161514

47111316202327334142444549 022234

77



• Conclusions

– In heavily pretreated patients with metastatic HER2-overexpressing (IHC 2+/3+) NSCLC, trastuzumab

deruxtecan demonstrated promising activity and the safety profile was generally comparable to previous

findings

Nakagawa K, et al. J Thorac Oncol 2021;16(suppl):Abstr OA04.05

IHC 3+ (n=10) IHC 2+ (n=39) Overall (n=49)

ORR, n (%) [95%CI] 2 (20.0) [2.5, 55.6] 10 (25.6) [13.0, 42.1] 12 (24.5) [13.3, 38.9]

BOR, n (%)

CR 0 (0) 1 (2.6) 1 (2.0)

PR 2 (20.0) 9 (23.1) 11 (22.4)

SD 6 (60.0) 16 (41.0) 22 (44.9)

PD 1 (10.0) 10 (25.6) 11 (22.4)

NE 1 (10.0) 3 (7.7) 4 (8.2)

DCR, n (%) [95%CI] 8 (80.0) [44.4, 97.5] 26 (66.7) [49.8, 80.9] 34 (69.4) [54.6, 81.8]

Median DoR, mo (95%CI) 6.0 (NE, NE) 5.8 (3.2, NE) 6.0 (3.2, NE)

TRAEs, n (%) n=49

Any 44 (89.8)

Grade ≥3 27 (55.1)

Serious 8 (16.3)

Led to dose discontinuation 6 (12.2)

Led to dose reduction 16 (32.7)

Led to dose interruption 17 (34.7)

78

OA04.06: Neratinib in Pretreated EGFR Exon 18-Mutant Non-Small Cell Lung Cancer (NSCLC): Initial Findings From the SUMMIT Basket Trial – Boni V, et al

• Study objective

– To assess the efficacy and safety of neratinib in a cohort of patients with NSCLC and EGFR exon 18 mutation

*Prophylaxis with loperamide (first 6 weeks, then PRN) mandatory Boni V, et al. J Thorac Oncol 2021;16(suppl):Abstr OA04.06

Primary endpoint


Secondary endpoints

• DoR, CBR, PFS, safety

Neratinib 240 mg/day PO*


• Lung cancer

• EGFR exon 18 mutation

• Treatment naïve or previously

treated with EGFR or pan-HER TKIs

• Prior chemotherapy and/or

checkpoint inhibitors permitted

• ECOG PS 0–2

(n=11)

79


• Key results

Boni V, et al. J Thorac Oncol 2021;16(suppl):Abstr OA04.06

Efficacy evaluable (n=11) TKI pretreated (n=10)

Confirmed ORR, % (95%CI) 36 (11, 69) 40 (12, 74)

CR, n 0 0

PR, n 4 4

BOR, % (95%CI) 54 (23, 83) 60 (26, 88)

CR, n 0 0

PR, n 6 6

Median DoR, mo (95%CI) 7.5 (4.0, NE) 7.5 (4.0, NE)

CBR, % (95%CI) 73 (39, 94) 80 (44, 97)

CR or PR, n 4 4

SD ≥16 weeks, n 4 4

mPFS, mo (95%CI) 6.9 (2.1, NA) 9.1 (3.7, NA)

80



• Conclusions

– In pretreated patients with NSCLC and EGFR exon 18 mutation, neratinib demonstrated promising early

clinical activity and was generally well-tolerated

Boni V, et al. J Thorac Oncol 2021;16(suppl):Abstr OA04.06

TEAEs, n (%) Any grade Grade ≥3

Diarrhoea 5 (45.5) 0 (0)

Vomiting 4 (36.4) 0 (0)

Constipation 3 (27.3) 0 (0)

Nausea 3 (27.3) 0 (0)

Appetite decreased 3 (27.3) 1 (9.1)

Dizziness 2 (18.2) 0 (0)

Hypertension 2 (18.2) 0 (0)

Dry mouth 2 (18.2) 0 (0)

Fatigue 2 (18.2) 0 (0)

81

MA11.07: Phase 1/2 TRIDENT-1 Study of Repotrectinib in Patients with ROS1+ or NTRK+ Advanced Solid Tumors – Cho BC, et al

• Study objective

– To assess the efficacy and safety of repotrectinib in patients with ROS1 or NTRK mutated advanced solid

tumours

Cho BC, et al. J Thorac Oncol 2021;16(suppl):Abstr MA11.07

Primary endpoint


Secondary endpoints

• DoR, PFS, safety

Cohort 2: ROS1+ NSCLC (n=60)

1 prior ROS1 TKI and 1 platinum-based chemotherapy


2 prior ROS1 TKI and no prior chemotherapy


ROS1 TKI-naïve


• Advanced solid tumours

• ROS1 or NTRK1/2/3 fusion

(n=185)


1 prior ROS1 TKI and no prior chemotherapy

Repotrectinib

160 mg/day

for 14 days

followed by

160 mg BIDCohort 5: NTRK+ advanced solid tumours (n=55)

TRK TKI-naïve

Cohort 6: NTRK+ advanced solid tumours (n=40)

TRK TKI-pretreated

82


• Key results


Overall response (n=22)

Phase 2

(n=15)

Phase 1 + 2

(n=22)

Confirmed ORR, % (95%CI) 93 (68, 100) 91 (71, 99)

N=22 patients with baseline and at least two post

baseline scans

• n=15 Phase 2 patients

• n=7 Phase 1 patients treated at or above the

Phase 2 recommended dose

As of 31 Dec 2020, the 16th patient in Phase 2 has an

unconfirmed PR and is on treatment awaiting a second

post-baseline confirmatory scan

Max.

% c

hange in b

aselin

e

in tum

in t

um

ou

r siz

e

–0

–20

–40

–60

–80

–100Phase 1

A Patient previously confirmed partial response

now in unconfirmed CR on treatment

A

83



• Conclusions

– In patients with ROS1+ advanced NSCLC, repotrectinib demonstrated promising activity in the TKI-naïve

cohort and was generally well-tolerated


ORR, n/N (%) [95%CI]

Cohort 1 6/7 (86) [42, 100]

Cohort 2 2/5 (40) [5, 85]

Cohort 3 2/5 (40) [5, 85]

Cohort 4 4/6 (67) [22, 96]

Cohort 5 NR

Cohort 6 3/6 (50) [12, 88]

Grade 3 TRAEs, n (%) All treated patients (n=185)

Anaemia 6 (3.2)

Dizziness 4 (2.2)

Dyspnoea 1 (0.5)

Muscular weakness 1 (0.5)

Other malignancies

SCLC, mesothelioma and thymic epithelial tumors

85

PS01.11: Nivolumab Versus Placebo in Relapsed Malignant Mesothelioma: The CONFIRM Phase 3 Trial – Fennell D, et al

• Study objective

– To assess the efficacy and safety of nivolumab in patients with relapsed malignant mesothelioma

Fennell D, et al. J Thorac Oncol 2021;16(suppl):Abstr PS01.11

R

2:1

PD/toxicity/

withdrawal

PD/toxicity/

withdrawal

Stratification

• Histology (epithelioid vs. non-epithelioid)


• Mesothelioma

• >1 prior line of therapy

• ECOG PS 0–1

(n=332)Placebo

(n=111)

Nivolumab 240 mg IV D1 q2w

(n=221)

Co-primary endpoints

• OS, PFS (investigator assessed)

Secondary endpoint

• Response, QoL, safety

86


• Key results


Overall survival

Pro

port

ion a

live, %

1.00

0.75

0.50

0.25

0

Time to death, months

302724211815129630

19101924405895132191221

22235918295390111

No. at risk

Nivolumab

Placebo

Nivolumab

(n=221)

Placebo

(n=111)

mOS, mo (95%CI) 9.2 (7.5, 10.8) 6.6 (5.0, 7.5)

12-mo OS, % (95%CI) 39.5 (32.5, 46.3) 26.9 (18.2, 36.4)

HR (95%CI); p-value 0.72 (0.55, 0.94); 0.018

Median follow-up: Nivolumab: 17.1 months; placebo: 14.2 months

Number of events: Nivolumab: n=151; placebo: n=81Nivolumab

Placebo

87





Pro

po

rtio

n a

live

with

no

pro

gre

ssio

n,

%

1.00

0.75

0.50

0.25

0

Time to death, months

302724211815129630

0134513264266108221

000002482136111

No. at risk

Nivolumab

Placebo

Nivolumab

Placebo

Nivolumab

(n=221)

Placebo

(n=111)

mPFS, mo (95%CI) 3.0 (7.5, 10.8) 1.8 (5.0, 7.5)

12-mo PFS, % (95%CI) 14.5 (10.2, 19.7) 4.9 (1.8, 10.6)

HR (95%CI); p-value 0.61 (0.48, 0.77); <0.001

88




Nivolumab Placebo

PD-L1 positive n 56 24

mOS, mo (95%CI) 8.0 (7.1, 12.2) 8.7 (5.1, 15.1)

12-mo OS, % (95%CI) 38.6 (25.1, 51.8) 43.6 (21.6, 63.8)

HR (95%CI); p-value 0.95 (0.51, 1.76); 0.864

PD-L1 negative n 94 60

mOS, mo (95%CI) 9.0 (6.6, 11.1) 6.4 (4.5, 8.5)

12-mo OS, % (95%CI) 36.6 (26.4, 46.7) 26.0 (15.1, 38.3)

HR (95%CI); p-value 0.74 (0.51, 1.08); 0.115

Epithelioid n 195 98

mOS, mo (95%CI) 9.4 (7.7, 10.9) 6.6 (5.0, 8.0)

12-mo OS, % (95%CI) 40.0 (32.6, 47.3) 26.7 (17.5, 36.8)

HR (95%CI); p-value 0.71 (0.53, 0.95); 0.021

Non-epithelioid n 26 13

mOS, mo (95%CI) 5.9 (3.6, 18.4) 6.7 (1.8, NA)

12-mo OS, % (95%CI) 34.6 (15.8, 54.3) 30.8 (9.5, 55.4)

HR (95%CI); p-value 0.79 (0.35, 1.79); 0.572

89



• Conclusions

– In patients with relapsed malignant mesothelioma, nivolumab demonstrated significant improvements in

survival compared with placebo and was generally well-tolerated


AEs, n (%)

Nivolumab (n=221) Placebo (n=111)

Any grade Grade ≥3 Any grade Grade ≥3

Any 207 (94) 99 (45) 104 (94) 47 (42)

Serious 90 (41) 80 (36) 49 (44) 43 (39)

90

OA09.06: Nivolumab in Recurrent Malignant Pleural Mesothelioma: Real-World Data From Expanded Access Program In The Netherlands – Belderbos RA, et al

• Study objective

– To assess the efficacy and safety of nivolumab in patients with recurrent malignant pleural mesothelioma in a

real-world setting

*As part of an Expanded Access Program since 2017 Belderbos RA, et al. J Thorac Oncol 2021;16(suppl):Abstr OA09.06

Endpoints

• PFS, OS, safety

Nivolumab 3 mg/kg*


• Malignant pleural mesothelioma

• Any PD-L1 expression

• Disease progression after ≥1

line of chemotherapy

• ECOG PS 0–1

(n=107)

91


• Key results

Belderbos RA, et al. J Thorac Oncol 2021;16(suppl):Abstr OA09.06

Overall survivalProgression-free survival

1815129630

PF

S p

rob

ab

ility

1.00

0.75

0.50

0.25

0

No. at risk 2411225078107

Months

Median PFS: 2.3 months

6-month PFS: 23%

1815129630

OS

pro

ba

bili

ty

1.00

0.75

0.50

0.25

0

No. at risk 2411225078107

Months

Median OS: 6.7 months

6-month OS: 60%

12-month OS: 31%

92



• Conclusions

– In patients with recurrent malignant pleural mesothelioma in a real-world setting, nivolumab did not provide

the same benefits as observed in clinical trials with worse ORR and mOS, particularly in those with no PD-L1

expression or low albumin levels

Belderbos RA, et al. J Thorac Oncol 2021;16(suppl):Abstr OA09.06

Nivolumab

mOS, mo Epithelioid (n=78) 7.4

Non-epithelioid (n=22) 4.8

PR (n=11) NR

SD (n=28) 10.2

PD (n=39) 6.4

Albumin <38 mg/dL (n=22) 2.5

Albumin >38 mg/dL (n=21) 8.0

Nivolumab

mPFS, mo PD-L1 positive (n=11) 4.2

PD-L1 negative (n=22) 1.7

ORR,% PD-L1 positive (n=11) 36

PD-L1 negative (n=22) 9

OR (95%CI); p-value 1.31 (1.00,1.72); 0.05

93

OA11.03: A Phase 1 Study of AMG 757, Half-Life Extended Bispecific T-Cell Engager (BiTE®)Immune Therapy Against DLL3, in SCLC – Owonikoko TK, et al

• Study objective

– To assess the efficacy and safety of AMG 757, a bispecific T-cell engager immune therapy against DLL3, in

patients with SCLC

Owonikoko TK, et al. J Thorac Oncol 2021;16(suppl):Abstr OA11.03

Endpoints

• Antitumor activity, PK, safety

AMG 757 0.003–30.0 mg IV

q2w with/out step dose


• SCLC

• ≥1 line systemic therapy

• Disease progression or recurrence after

≥1 platinum-based chemotherapy

• ECOG PS 0–2

(n=40)

94


• Key results

*Step dosing; †PR is unconfirmed; ‡patient had an initial PR but was not confirmed at next scan Owonikoko TK, et al. J Thorac Oncol 2021;16(suppl):Abstr OA11.03

Modified RECIST v1.1

response, n (%) n=51

PR confirmed 7 (14)

0.3 mg target dose 1/12 (8)

1 mg target dose 1/8 (13)



PR unconfirmed 1 (2)

30 mg target dose 1 (2)

SD 11 (22)

DCR, % 37

100

80

60

40

20

0

–20

–40

–60

–80

–100

Be

st %

ch

an

ge

fro

m b

ase

line

in s

um

of d

iam

ete

rs

PD

PD

PDPD PD PD PD PD

PD PD PD PD PD PD PD PD PD NE SD

SDSD PD SD SD

SD

SDSD

SD

SD‡

PD PD

PDPR

PR PRPR

PRPR

PR†PR

0.003mg 0.01mg 0.03mg 0.1mg 0.3mg

1mg 3mg* 10mg* 30mg*

Patients with target lesion and evaluable post-baseline assessment, including sum of diameters (n=42)

PD

SD

95



• Conclusions

– In patients with SCLC, AMG 757 demonstrated activity and had an manageable safety profile

*One patient with grade 5 pneumonitis Owonikoko TK, et al. J Thorac Oncol 2021;16(suppl):Abstr OA11.03

TRAEs occurring in ≥10% of patients, n (%) All grades Grade ≥3

Any 41 (79) 12 (23)

CRS 23 (44) 1 (2)*

Pyrexia 10 (19) 0 (0)

Fatigue 7 (14) 0 (0)

Anaemia 5 (10) 1 (2)

Nausea 5 (10) 0 (0)

96

OA11.06: IMpower133: Exploratory Analysis of Maintenance Therapy in Patients With Extensive-Stage Small-Cell Lung Cancer – Reck M, et al

• Study objective

– To assess the efficacy and safety of atezolizumab vs. placebo in patients with extensive-stage SCLC who

had reached maintenance therapy phase of the IMpower133 study

*Carboplatin AUC 5 mg/mL/min IV q3w; etoposide 100 mg/m2 IV D1–3 q3w for four 21-day cycles Reck M, et al. J Thorac Oncol 2021;16(suppl):Abstr OA11.06

R

1:1

PD/loss of

benefit

PD/loss of

benefit

Stratification

• Sex (male vs. female)

• ECOG PS (0 vs. 1)

• Brain metastases (yes vs. no)


• Measureable extensive-stage

SCLC

• No prior systemic therapy

• Treated asymptomatic brain

metastases were eligible

• ECOG PS 0–1

(n=403)

Placebo +

carboplatin + etoposide*

(n=202)

Atezolizumab 1200 mg IV D1 q3w

+ carboplatin + etoposide*

(n=201)

Placebo

Atezolizumab

Primary endpoints

• OS, PFS (RECIST v1.1)

Secondary endpoint

• Safety

Induction Maintenance

97


• Key results


Atezolizumab

+ CP/ET (n=154)

Placebo

+ CP/ET (n=164)

OS from start of maintenance, HR (95%CI) 0.59 (0.43, 0.81)

mOS from start of maintenance, months (95%CI) 12.5 (9.0, 14.5) 8.4 (7.0, 9.4)

mOS from randomisation, months (95%CI) 15.7 (12.3, 17.6) 11.3 (10.1, 12.2)

Atezolizumab

+ CP/ET (n=154)

Placebo

+ CP/ET (n=164)

PFS from start of maintenance, HR (95%CI) 0.64 (0.50, 0.82)

mPFS from start of maintenance, months (95%CI) 2.6 (2.3, 2.9) 1.8 (1.4, 2.3)

mPFS from randomisation, months (95%CI) 5.5 (4.9, 5.6) 4.5 (4.3, 5.4)

Overall survival Progression-free survival

OS

, %

100

80

60

40

20

0

Time, months

181614121086420 242220

51120324355708497110118127138150154154154154154 123

No. at risk

Atezo

+CP/ET

Placebo

+CP/ET3813202532557589103118131145154163164164164164 223

Atezolizumab + CP/ET

Placebo + CP/ET

PF

S, %

100

80

60

40

20

0

Time, months

181614121086420 242220

2331111142025283140455387134143152154154 112

No. at risk

Atezo

+CP/ET

Placebo

+CP/ET33568813142022274176142157163164164

Atezolizumab + CP/ET

Placebo + CP/ET

98



• Conclusions

– In patients with extensive-stage SCLC, maintenance atezolizumab + carboplatin/etoposide contributed to

survival benefit over carboplatin/etoposide alone and safety was comparable between the two treatment arms

– Higher age, higher LDH level and reduced performance status were poor prognostic factors to reach the

maintenance therapy phase in both arms (data not shown)Reck M, et al. J Thorac Oncol 2021;16(suppl):Abstr OA11.06

AEs, n (%)

From randomisation (induction + maintenance) From start of maintenance

Atezolizumab (n=155) Placebo (n=163) Atezolizumab (n=155) Placebo (n=163)

Any 155 (100) 159 (98) 127 (82) 118 (72)

TRAE 151 (97) 153 (94) 76 (49) 61 (37)

Atezolizumab/placebo 100 (65) 86 (53) 64 (41) 41 (25)

Grade 3–4 105 (68) 105 (64) 43 (28) 37 (23)

Treatment-related grade 5 0 (0) 1 (<1) 0 (0) 1 (<1)

Serious 52 (34) 47 (29) 24 (15) 19 (12)

Led to dose modification/interruption 111 (72) 100 (61) 30 (19) 17 (10)

Atezolizumab/placebo 96 (62) 85 (52) 28 (18) 17 (10)

Immune-related 64 (41) 46 (28) 41 (26) 24 (15)

99

MA12.10: Treatment and Survival Differences in Patients with Large Cell Neuroendocrine Carcinoma of the Lung: A SEER Database Analysis – Chen J-H, et al

• Study objective

– To assess the differences in treatment and survival and identify predictors of response in patients with large

cell neuroendocrine carcinoma (LCNEC) of the lung

• Methods

– Data for 2838 patients with LCNEC from the Surveillance, Epidemiology, and End-Results (SEER) database

were collected to evaluate age, sex, race and tumour site, size, grade and stage

– Factors associated with OS and cancer-specific survival (CSS) were assessed using multivariate logistic and

Cox regression

Chen J-H, et al. J Thorac Oncol 2021;16(suppl):Abstr MA12.10

100S = surgery, R = radiotherapy, C = chemotherapy


• Key results

Chen J-H, et al. J Thorac Oncol 2021;16(suppl):Abstr MA12.10

Analysed overall survival and cancer-specific survival in different stages

OS rate, % 1-year 3-year 5-year

S 72.4 52.4 42.3

S + R 62.8 30.1 16.9

S + C 83.3 57.2 48.5

R + C 42.7 12.1 8.0

CSS rate, % 1-year 3-year 5-year

S 83.3 61.6 53.5

S + R 62.8 31.5 17.6

S + C 85.9 62.7 55.2

R + C 45.4 15.3 9.5

OS

, %

100

80

60

40

20

0

150100500

P<0.0001Stage 1

Stage 2

Stage 3

Stage 4

Ove

rall

CS

S, %

100

80

60

40

20

0

150100500

P<0.0001Stage 1

Stage 2

Stage 3

Stage 4

OS

, %

100

80

60

40

20

0

150100500

S

S + R

S + C

R + C

Effects of treatments in patients with L-LCNEC

Ove

rall

CS

S, %

100

80

60

40

20

0

150100500

S

S + R

S + C

R + C

Survival time, months Survival time, months

101



• Conclusions

– In patients with large cell neuroendocrine carcinoma of the lung, surgery and chemotherapy demonstrated

significant improvements in OS and CSS

– Age ≥80 years, stage III and IV or tumour size >5 cm were found to be independent poor prognostic factors Chen J-H, et al. J Thorac Oncol 2021;16(suppl):Abstr MA12.10

Characteristic n (%)

Univariate analysis Multivariate analysis

HR (95%CI) p-value HR (95%CI) p-value

Age, years <60

60–79

≥80

796 (28.0)

1774 (62.5)

268 (9.5)

Reference

1.315 (1.111, 1.556)

2.661 (1.919, 3.688)

0.001

<0.0001

Reference

1.352 (1.136, 1.609)

1.841 (1.313, 2.582)

0.001

<0.0001

Sex Male

Female

1591 (56.1)

1247 (43.9)

Reference

0.815 (0.707, 0.940) 0.005

Reference

0.775 (0.664, 0.905) 0.001

Stage I

II

III

IV

664 (23.4)

162 (5.7)

556 (19.6)

1391 (49.0)

Reference

1.896 (1.293, 2.781)

3.795 (2.910, 4.948)

6.763 (5.417, 8.444)

0.001

<0.0001

<0.0001

Reference

1.669 (1.007, 2.765)

2.053 (1.371, 3.074)

3.878 (2.595, 5.796)

0.047

<0.0001

<0.0001

Tumour size ≤3

3–5

>5

Unknown

977 (34.4)

641 (22.6)

735 (26.5)

467 (16.5)

Reference

1.255 (1.031, 1.527)

1.992 (1.651, 2.404)

2.675 (2.162, 3.310)

0.024

<0.0001

<0.0001

Reference

1.182 (0.902, 1.549)

1.391 (1.071, 1.808)

1.362 (1.004, 1.848)

0.226

0.013

0.047

Surgery No

Yes

1861 (65.6)

977 (34.4)

Reference

0.199 (0.166, 0.240) <0.0001

Reference

0.553 (0.397, 0.770) <0.0001

Chemotherapy No

Yes

1338 (47.1)

1500 (52.9)

Reference

0.653 (0.567, 0.752) <0.0001

Reference

0.455 (0.392, 0.528) <0.0001

102

MA12.11: What Regimen Should Be Chosen for Pulmonary Large Cell Neuroendocrine Carcinoma? A Systemic Review and Meta-Analysis – He J, et al

• Study objective

– To assess the outcomes of different regimens for patients with pulmonary large cell neuroendocrine

carcinoma (LCNEC)

• Methods

– A search of electronic databases was conducted to identify studies that provided prognostic outcomes of

SCLC and NSCLC regimen in patients with LCNEC

– In total 6 studies were identified that included 446 patients, 213 with NSCLC and 165 with SCLC received 1L

chemotherapy, while 42 with NSCLC and 26 with SCLC received adjuvant chemotherapy

He J, et al. J Thorac Oncol 2021;16(suppl):Abstr MA12.11

103


• Key results

He J, et al. J Thorac Oncol 2021;16(suppl):Abstr MA12.11

First-line chemotherapy

Author Year HR (95%CI) % Weight

Rossi

Sun

Naidoo

Derks 1

Derks 2

Eldessouki

Zhang

Overall (I-squared

= 96.7%, p=0.000)

2005

2012

2016

2017

2017

2018

2019

0.05 (0.02, 0.10)

0.27 (0.13, 0.52)

9.69 (4.35, 21.57)

2.68 (1.83, 3.92)

0.59 (0.31, 1.10)

0.89 (0.32, 2.49)

0.12 (0.07, 0.22)

0.73 (0.58, 0.92)

9.17

11.43

8.25

36.13

13.18

4.95

16.87

100.00

0.1 0.5 2 101SCLC regimen NSCLC regimen

Adjuvant chemotherapy

Author Year HR (95%CI) % Weight

Rossi

Zheng

Overall (I-squared

= 80.2%, p=0.025)

2005

2019

0.02 (0.01, 0.04)

0.08 (0.03, 0.23)

0.03 (0.02, 0.07)

55.16

44.84

100.00

0.005 0.05 0.5 5SCLC regimen NSCLC regimen

Overall survival

104



• Conclusions

– In patients with large cell neuroendocrine carcinoma, 1L SCLC therapies demonstrated improvements in OS

and PFS, while adjuvant SCLC chemotherapy regimens provided improvement in OS

– Conclusions are limited as based on huge heterogeneity of results – further collection of controlled data is of

paramount importance He J, et al. J Thorac Oncol 2021;16(suppl):Abstr MA12.11

Progression-free survival for first-line chemotherapy

Year HR (95%CI) % WeightAuthor

Sun

Naidoo

Derks 1

Derks 2

Zhang

Overall (I-squared

= 96.7%, p=0.000)

2012

2016

2017

2017

2019

0.51 (0.28, 1.01)

0.89 (0.40, 1.95)

1.82 (1.22, 2.71)

0.54 (0.28, 1.00)

0.34 (0.23, 0.48)

0.68 (0.54, 0.85)

10.71

7.99

30.83

12.21

38.25

100.00

0.25 0.5 21SCLC regimen NSCLC regimen

IASLC 2020 World Conference on Lung Cancer

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