Clinical efficacy of atezolizumab (atezo) in biomarker subgroups by SP142, SP263 and 22C3 PD-L1 immunohistochemistry (IHC) assays and by blood tumour mutational burden (bTMB): Results from the IMpower110 study

Date

12 Dec 2019

Session

Proffered Paper session 1

Presenters

Roy S. Herbst

Authors

R.S. Herbst1, F. de Marinis2, G. Giaccone3, N. Reinmuth4, A. Vergnenegre5, C.H. Barrios6, M. Morise7, E. Felip8, Z. Andric9, S. Geater10, M. Ozguroglu11, S. Mocci12, M. McCleland12, W. Zou12, I. Enquist12, K. Komatsubara12, Y. Deng12, H. Kuriki12, D.R. Spigel13, J. Jassem14

Author affiliations

  • 1 Medical Oncology, Yale University School of Medicine, 06520 - New Haven/US
  • 2 Thoracic Oncology Dept., Istituto Europeo di Oncologia, 20141 - Milan/IT
  • 3 Oncology, Weill Cornell Medical Center, New York/US
  • 4 Thoracic Oncology, Asklepios Lung Clinic, Munich-Gauting/DE
  • 5 Department Of Medical Oncology, University of Limoges, Limoges/IT
  • 6 School Of Medicine, PUCRS-Pontifícia Universidade do Rio Grande do Sul, 90619-900 - Porto Alegre/BR
  • 7 Department Of Respiratory Medicine, Nagoya University Graduate School of Medicine, Nagoya/JP
  • 8 Medical Oncology Department, Vall d’Hebron University Hospital, 8035 - Barcelona/ES
  • 9 Oncology, Clinical Hospital Center Bezanijska Kosa, Belgrade/RS
  • 10 Oncology, Prince of Songkla University, Hat Yai/TH
  • 11 Oncology, University Of Istanbul Cerrahpasa Medical Faculty, 34096 - Istanbul/TR
  • 12 Oncology, Genentech, Inc, South San Francisco/US
  • 13 Medical Oncology, Sarah Cannon Research Institute, Nashville/US
  • 14 Dept. Of Oncology And Radiotherapy, Medical University of Gdansk, Gdansk/PL
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Background

The Phase III IMpower110 study (NCT02409342) is evaluating atezo (anti–PD-L1) monotherapy as 1L treatment (tx) in PD-L1–selected patients (pts) with NSCLC independent of tumour histology. IMpower110 met its primary endpoint with significant OS improvement in PD-L1–high (TC3 or IC3; ≥ 50% tumour cell [TC] or ≥ 10% tumour-infiltrating immune cell [IC]; VENTANA SP142 IHC assay) wild-type (WT; EGFR/ALK-negative) pts (HR, 0.59 [95% CI: 0.40, 0.89]; P = 0.0106). Efficacy analyses in prespecified biomarker subgroups by the SP263 and 22C3 PD-L1 IHC assays and bTMB are reported.

Methods

IMpower110 enrolled 572 chemo-naive pts with stage IV NSCLC, PD-L1 ≥ 1% TC or IC (TC1/2/3 or IC1/2/3; SP142), measurable disease by RECIST 1.1 and ECOG PS 0-1. Pts were randomised 1:1 to receive atezo 1200 mg IV q3w or platinum-based chemo (4 or 6 21-day cycles). OS (primary endpoint) was tested hierarchically in WT pts. Additional analyses included OS and PFS in the SP263 and 22C3 PD-L1 IHC and bTMB populations. PD-L1 cutoffs of ≥ 1% and ≥ 50% tumour proportion score (TPS) for 22C3 and ≥ 1% and ≥ 50% TC for SP263 were evaluated; bTMB cutoffs were ≥10, ≥ 16 and ≥ 20.

Results

Biomarker-evaluable populations (BEP) in the TC1/2/3 or IC1/2/3 WT population (SP142; 554) included 534 (22C3), 546 (SP263) and 389 (bTMB) pts. Baseline characteristics in the IHC and bTMB BEP subgroups were generally balanced. OS and PFS in the PD-L1–high (TC3 or IC3; ≥ 50% TPS; ≥ 50% TC) subgroups favoured atezo (OS data shown in table). Stepwise OS and PFS improvement, favouring atezo, was seen up to bTMB ≥ 16; no further benefit was seen at ≥ 20.

Conclusion

Pt subgroups defined as PD-L1–high by all 3 IHC assays (SP142, 22C3, SP263) had similar OS and PFS benefit with atezo, despite the different assay sensitivities and scoring algorithms. Enrichment in clinical benefit, favouring atezo, was also seen in bTMB positive subgroups. Atezo monotherapy is a potential new 1L tx option for pts with PD-L1–high NSCLC.

Subgroup

Median OS

HRa
(95% CI)

Atezo

Chemo

n

mo

n

mo

VENTANA SP142 (n = 554)

TC1/2/3 or IC1/2/3 WT

277

17.5

277

14.1

0.83
(0.65, 1.07)

TC3 or IC3 WT

107

20.2

98

13.1

0.59
(0.40, 0.89)

Dako 22C3 (n = 534)

22C3 BEP

268

17.5

266

14.1

0.82
(0.64, 1.06)

≥ 50% TPS

134

20.2

126

11.0

0.60
(0.42, 0.86)

≥ 1% TPS

213

17.8

201

14.0

0.73
(0.55, 0.97)

VENTANA SP263 (n = 546)

SP263 BEP

271

17.2

275

14.9

0.85
(0.66, 1.09)

≥ 50% TC

150

19.5

143

16.1

0.71
(0.50, 1.00)

≥ 1% TC

212

17.8

210

14.0

0.77
(0.58, 1.02)

Foundation Medicine bTMB (n = 389)

bTMB BEP

196

13.3

193

15.3

0.98
(0.74, 1.30)

≥ 10

92

11.2

83

10.3

0.87
(0.58, 1.30)

≥ 16

42

13.9

45

8.5

0.75
(0.41, 1.35)

≥ 20

27

17.2

29

10.5

0.77
(0.36, 1.64)

a Stratified OS HRs for SP142 only.

Clinical trial identification

NCT02409342

Editorial acknowledgement

Medical writing assistance for this abstract was provided by Kia C. E. Walcott, PhD, of Health Interactions, and
funded by F. Hoffmann-La Roche, Ltd

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Invited Discussant LBA3

Presenter: Alessandra Curioni

Session: Proffered Paper session 1

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