1322P - Biomarkers associated with clinical activity of PD-L1 blockade in non-small cell lung cancer (NSCLC) patients (pts) in a Phase I study of MPDL3280A

Date 27 September 2014
Event ESMO 2014
Session Poster Display session
Topics Immunotherapy
Pathology/Molecular Biology
Translational Research
Non-small-cell lung cancer
Basic Scientific Principles
Basic Principles in the Management and Treatment (of cancer)
Presenter Jean-Charles Soria
Citation Annals of Oncology (2014) 25 (suppl_4): iv426-iv470. 10.1093/annonc/mdu349
Authors J. Soria1, S. Gettinger2, M.S. Gordon3, R.S. Heist4, L. Horn5, D.R. Spigel6, M. Kowanetz7, A. Mokatrin8, Y. Xiao9, A. Sandler10, E. Felip11
  • 1Early Clinical Trials, Institut de Gustave Roussy, 94805 - Villejuif/FR
  • 2Thoracic Oncology Program, Yale University School of Medicine, New Haven/US
  • 3Pinnacle Oncology Hematology, Oncology Research Associates, Scottsdale/US
  • 4Thoracic Oncology, Massachusetts General Hospital Cancer Center, 02114 - Boston/US
  • 5Thoracic Oncology Program, Vanderbilt-Ingram Cancer Center, 37232 - Nashville/US
  • 6Lung Cancer Research Program, Sarah Cannon Research Institute, 37203 - Nashville/US
  • 7Oncology Biomarker, Genentech, 94080 - South San Francisco/US
  • 8Oncology Biostatistics, Genentech, Inc., 94080 - South San Francisco/US
  • 9Biostatistics, Genentech, Inc, 94080 - South San Francisco/US
  • 10Oncology, Genentech, Inc., 94080 - South San Francisco/US
  • 11Oncologia Médica, Vall d`Hebron University Hospital Institut d'Oncologia, 08035 - Barcelona/ES



Cancers can evade immune surveillance by upregulating PD-L1. MPDL3280A, a human anti-PD-L1 mAb with an engineered Fc domain, blocks PD-L1 binding to its receptors PD-1 and B7.1 on activated T cells. Predictive factors of response to PD-L1 blockade are not well characterized. Here, we examine biomarkers that might predict MPDL3280A response.


NSCLC pts received MPDL3280A 1-20 mg/kg IV q3w. Pts were treated for ≤ 1 y. Responses (ORR, including unconfirmed) were assessed by RECIST v1.1. FFPE tumor samples were analyzed by IHC and Genentech immunochip measuring 90 immune-related genes to characterize the tumor immune microenvironment at baseline. Tumor-infiltrating immune cells (ICs) or tumor cells (TCs) were scored as IHC 0, 1, 2 or 3 if < 1%, ≥ 1% but < 5%, ≥ 5% but < 10%, or ≥ 10% of cells expressed PD-L1, respectively. Positivity for PD-L2, IDO1, LAG3, TIM3, CTLA4, B7-H3 and B7-H4 was by gene expression ≥ median.


As of Apr 30, 2013, 53 NSCLC pts dosed by Oct 1, 2012, were evaluable for efficacy. In this trial ≈ 30% of NSCLC pts were PD-L1 IHC 2 or 3. ORRs were associated with PD-L1 expression in ICs (p = .02): IHC 3: ORR 83% (5/6), IHC 2: 14% (1/7), IHC 1: 15% (2/13), IHC 0: 20% (4/20). PD-L1 expression in TCs did not significantly correlate with response (p = .92). The 24-wk PFS rate was 45%. Expression of checkpoint markers was a weaker predictor of MPDL3280A response and did not appear to confer MPDL3280A resistance in PD-L1 IHC2/3 pts (Table). Additionally, elevated IFNɣ expression, and IFNɣ-inducible genes (e.g., IDO1 and CXCL9), did not appear to associate with MPDL3280A response.

Response Rates in Biomarker-Defined Subpopulationsa,b

Subpopulation n ORR, % Subpopulation n ORR, %
PD-L1 IHC 2 or 3 10 50
CTLA4 + 18 39 PD-L1 IHC 2 or 3; CTLA4 + 6 67
PD-L2 + 20 30 PD-L1 IHC 2 or 3; PD-L2 + 8 63
LAG3 + 18 28 PD-L1 IHC 2 or 3; LAG3 + 6 67
IDO1 + 19 26 PD-L1 IHC 2 or 3; IDO1 + 8 63
B7-H3 + 20 25 PD-L1 IHC 2 or 3; B7-H3 + 5 80
TIM3 + 20 25 PD-L1 IHC 2 or 3; TIM3 + 6 67
B7-H4 + 18 22 PD-L1 IHC 2 or 3; B7-H4 + 5 40

a For pts with both PD-L1 IHC and immunochip data only (N = 37). b PD-L1 IHC scores based on ICs.


These data suggest PD-L1 expression has a stronger correlation with ORR compared to other immune checkpoints. PD-L1 appears to be a leading predictive biomarker for response to MPDL3280A. These findings help provide a better understanding of biomarkers and MPDL3280A clinical activity.


J-C. Soria has received honoraria from Roche/Genentech; M. Gordon has served as an advisor/consultant to and has received research funding from Roche/Genentech; R.S. Heist has received clinical research funding to her institution from Roche, GSK, EMD Serono, Exelixis and Debiopharm; L. Horn: Research funding from Astellas. Served as an adviser for Bristol Myers Squibb, Clovis, Helix bio (compensated) and PUMA, Xcovery (uncompensated). Steering Committee: Bayer (Uncompensated). Received honoraria from Boehringer Ingelheim; D.R. Spigel has served in an uncompensated role as advisor to Genentech; M. Kowanetz, A. Mokatrin, Y. Xiao and A. Sandler: is an employee of Genentech, Inc.; E. Felip has served as an advisor to BI, Novartis, Roche, BMS and Eli Lilly. All other authors have declared no conflicts of interest.