1171P - The SP142 PD-L1 IHC assay for atezolizumab (atezo) reflects pre-existing immune status in NSCLC and correlates with PD-L1 mRNA

Date 10 October 2016
Event ESMO 2016 Congress
Session Poster display
Topics Immunotherapy
Therapy
Presenter James Williams
Citation Annals of Oncology (2016) 27 (6): 401-406. 10.1093/annonc/mdw380
Authors J. Williams1, M. Kowanetz2, H. Koeppen3, Z. Boyd4, E.E. Kadel III3, D. Smith3, M. McCleland3, W. Zou5, P.S. Hegde6
  • 1Diagnostic Lead, Genentech, Inc, 94080 - South San Francisco/US
  • 2Oncology Biomarker Development, Genentech, Inc, 94080 - South San Francisco/AM
  • 3Oncology Biomarker Development, Genentech, Inc., 94080 - South San Francisco/US
  • 4Diagnostic Development, Genentech, Inc, 94080 - South San Francisco/US
  • 5Oncology Biomarker, Genentech, Inc., South San Francisco/US
  • 6Oncology Biomarker Department, Genentech, Inc., South San Francisco/US

Abstract

Background

PD-L1 expression as measured by the SP142 PD-L1 IHC assay is associated with improved efficacy with atezo in patients with NSCLC, including overall survival. In capturing PD-L1 on both tumor cells (TC) and tumor-infiltrating immune cells (IC), this assay is able to determine preexisting immune status, underscoring the predictive value of PD-L1 IHC. In this study, we further investigated intratumoral immune infiltration status by measuring T effector (Teff) gene signature and correlated PD-L1 mRNA expression with SP142 PD-L1 IHC.

Methods

Using the SP142 IHC assay, procured samples from NSCLC tumors were scored according to the percent of TC expressing PD-L1 (TC0 

Results

In 86 NSCLC specimens, mRNA levels for PD-L1 increased incrementally with higher PD-L1 IHC status, from 0 median expression for TC0 and IC0 tumors to 3.14 median expression for TC3 or IC3 tumors. A similar trend was seen for the Teff signature, with values increasing from 0 to 1.65 median expression with increasing IHC cutoffs (Table).

Conclusions

Results from the SP142 PD-L1 IHC assay associates with PD-L1 and Teff mRNA transcripts, reflecting pre-existing immunity associated with adaptive PD-L1 expression on IC as well as intrinsic PD-L1 expression on TC in NSCLC, thus providing an independent orthogonal correlation of IHC to gene expression. The value of mRNA gene expression as a predictive marker of efficacy for atezo in NSCLC is being studied in ongoing randomized trials of atezo.

PD-L1 IHC vs PD-L1 mRNA and T effector gene signature

PD-L1 IHC PD-L1 mRNA T Effectora
n Medianb expression 95% CI n Medianb expression 95% CI
TC0 and IC0 46 0 −0.22, 0.36 46 0 −0.39, 0.16
TC1 or IC1 22 0.89 0.53, 1.66 22 0.73 0.25, 0.95
TC2 or IC2 11 2.66 2.49, 2.85 11 1.53 0.55, 1.57
TC3 or IC3 7 3.14 1.4, 4.29 7 1.65 0.46, 1.95

a Includes CD8A, GZMA, GZMB, EOMES, CXCL9, CXCL10, TBX21. b Median expressions are log scale expression (−ΔCT) relative to the median of TC0 and IC0 group. Larger values indicate higher expression.

Clinical trial identification

Not applicable.

Legal entity responsible for the study

F. Hoffmann-La Roche, Ltd.

Funding

F. Hoffmann-La Roche, Ltd.

Disclosure

J. Williams, M. Kowanetz, H. Koeppen, Z. Boyd, E.E. Kadel III, D. Smith, M. McCleland, W. Zou, P.S. Hegde: Employee of Genentech.