441O - Preliminary safety and clinical activity of erlotinib plus atezolizumab from a Phase Ib study in advanced NSCLC

Date 17 December 2016
Event ESMO Asia 2016 Congress
Session Thoracic cancers
Topics Anticancer Agents
Non-Small-Cell Lung Cancer, Metastatic
Presenter Brigette Ma
Citation Annals of Oncology (2016) 27 (suppl_9): ix139-ix156. 10.1093/annonc/mdw594
Authors B.B.Y. Ma1, C.M. Rudin2, A. Cervantes3, A. Dowlati4, D. Costa5, P. Schmid6, R. Heist7, V.M. Villaflor8, I. Sarkar9, M.A. Huseni10, P. Foster11, C. O'Hear11, S. Gettinger12, B. Besse13
  • 1Phase I Clinical Trial Center, Chinese University of Hong Kong Prince of Wales Hospital, n/a - Hong Kong/HK
  • 2Thoracic Oncology Service, Memorial Sloan Kettering Cancer Center, New York/US
  • 3Dept. Medical Oncology, Hospital Clinico Universitario de Valencia, Valencia/ES
  • 4Hematology / Oncology, University Hospitals Case Medical Center, 44106 - Cleveland/US
  • 5Hematology / Oncology, Beth Israel Deaconess Medical Center, Boston/US
  • 6Centre For Experimental Cancer Medicine, Barts Cancer Institute, London/GB
  • 7Medical Oncoloy, Massachusetts General Hospital, 02114 - Boston/US
  • 8Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago/US
  • 9Biostatistics, Genentech, South San Francisco/US
  • 10Oncology Biomarkers Development, Genentech, South San Francisco/US
  • 11Product Development Oncology, Genentech, South San Francisco/US
  • 12Thoracic Oncology Program, Yale Cancer Center, 06520-8032 - New Haven/US
  • 13Cancer Medicine, Institut de Cancérologie Gustave Roussy, 94805 - Villejuif/FR



Erlotinib (E) targeted therapy in EGFR mutant non-small cell lung cancer (NSCLC) can effectively reduce tumor burden; however, the durability of response is limited due to development of resistance. The mPFS with E alone in 1L EGFR mutant patients (pts) is 9.7 mo (95% CI 8.4-12.3; Rosell, Lancet Oncol 2012). Single agent immunotherapy with atezolizumab (A) has shown promising activity in NSCLC. A inhibits PD-L1 interaction with PD-1 and B7.1 and may enhance and perpetuate antitumor immunity. As such, combining E with A may improve both clinical response and durability in EGFR-mutant NSCLC.


The safety stage included pts with NSCLC regardless of EGFR status; expansion stage included TKI-naive pts with tumors harboring activating EGFR mutations. Pts were enrolled regardless of PD-L1 status. E was dosed at 150 mg PO QD during a 7 d run-in and was continued with A dosed at 1200 mg IV Q3W during combination. The primary objective was evaluation of safety and tolerability; secondary objective was to evaluate clinical activity of the combination.


At data cutoff (April 11, 2016), 28 pts (safety stage, n = 8; expansion stage, n = 20) who had received ≥ 1 dose of E or A were evaluated for safety. Median age was 61 y (range, 47-84); median survival follow-up was 11.2 mo (range, 0.8-24.2). Treatment-related G3-4 AEs occurred in 39% of pts; most common A-related AEs were pyrexia and increased ALT (n = 2 each). No pneumonitis was reported. Treatment-related serious AEs occurred in 50% of pts; no G5 AEs occurred. 5 pts discontinued A due to treatment-emergent AEs. No DLTs were observed. Clinical activity was evaluated in pts from the expansion-stage (Table). Exploratory analyses of on-treatment immune biomarkers and PFS will be presented.


The combination of full dose E+A demonstrated a manageable safety profile. The early results of ORR and mPFS with the E+A combination are promising and further investigation is warranted.rn

Table: 441O Clinical activity of erlotinib + atezolizumab (per RECIST v1.1) n = 20

ORR (95% CI)75% (51%-91%)
CR, n (%)0
PR, n (%)15 (75%)
SD, n (%)3 (15%)
DCR (CR + PR + SD ≥ 24 wk) (95% CI)90% (68%-99%)
Median PFS (95% CI)11.3 mo (8.4-NE)
Median DoR (95% CI)9.7 mo (7.1-NE)

NE, not estimable.


Clinical trial indentification


Legal entity responsible for the study

F. Hoffmann-La Roche Ltd


F. Hoffmann-La Roche Ltd


C.M. Rudin: Paid consultant for BMS, Medivation, and Novartis. A. Cervantes: Consulting fees from: Merck Serono, Amgen, Servier, Roche, Lilly, Novartis Contracted research: Roche, Merck Serono. D. Costa: Consulting fees from Pfizer, Boehringer Ingelheim and Ariad Pharmaceuticals. R. Heist: Honoraria/consulting: Boehringer Ingelheim, Ariad. I. Sarkar, M.A. Huseni, P. Foster: Genentech employee. C. O\'Hear: Genentech Employee. Stocker/other ownership: Genentech/Roche. Research funding from Genentech. S. Gettinger: Research Support (to institution): Genentech, Celldex, BMS, Incyte, Ariad. B. Besse: Research grants fron Roche/Genentech. All other authors have declared no conflicts of interest.