Most patients (pts) with ES-SCLC receive platinum-based chemotherapy with etoposide, however median survival is
ES-SCLC pts received atezo IV q3w at 15 mg/kg or 1200 mg as part of a Ph Ia study (NCT01375842). Due to protocol amendments the first 5 pts were PD-L1 selected and the subsequent 12 were not PD-L1 selected. Initially treatment was to last up to 1 y though retreatment at PD was allowed. Later pts were treated until loss of clinical benefit. RECIST v1.1 and irRC assessments were used. PD-L1 expression was centrally evaluated using the VENTANA SP142 IHC assay. Teffector (Teff) gene signature (CD8A, GZMA, GZMB, EOMES, CXCL9, CXCL10, TBX21) and PD-L1 mRNA was measured (iChip).
As of Dec 15, 2015, 17 pts with a minimum follow-up of 6.7 mo, were safety/efficacy evaluable. 65% were male; 88% were ECOG PS 1. Median age was 63 y (range 44-80), and pts were heavily pretreated (65% ≥ 3 prior therapies). 65% pts had all grade (1-5) treatment-related AEs most often fatigue (24%). There were 8 related G3-5 AEs in 3 pts, including 1 G3 pneumonitis leading to treatment discontinuation and 1 G5 hepatic failure. Confirmed ORR by RECIST was 6% (1 PR with DOR of 7 mo, also irPR by irRC) and 24% by irRC. 4/17 pts received atezo for ≥ 6 mo, 2 of these for ≥ 12 mo. 1 irPR pt stopped atezo per protocol after 1 y and remained in irPR for an additional 1 y until PD. Upon retreatment, the patient again derived benefit and is still on atezo as of data cutoff, 2.6 y from first dose. mPFS by RECIST was 1.5 mo (95% CI: 1.2, 2.7), and mOS was 5.9 mo (95% CI: 4.3, 20.1). PD-L1 expression was low overall, consistent with published data. A trend toward greater clinical benefit was seen for Teff gene signature and PD-L1 mRNA.
These initial results in ES-SCLC demonstrate a tolerable safety profile with no new safety signals for atezo. Atezo also showed encouraging single-agent activity, based on the duration of clinical benefit in a subset of patients. Further studies of atezo in ES-SCLC are planned.
Clinical trial identification
Legal entity responsible for the study
F. Hoffmann-La Roche Ltd.
F. Hoffmann-La Roche Ltd.
L.V. Sequist: Consulting: uncompensated consulting with BI, Clovis, Merrimack, Novartis, Genentech, Taiho, and consulting with AZ, Ariad Research: BI, AZ, Clovis, Merrimack, Merck, Novartis, Genentech. A. Chiang: Genentech/Roche Advisory Board Research funding for trials: Boehringer Ingelheim, OncoMed, Millenium, Onyx. J. Gilbert: Research funding (for clinical trials, not salary) from AZ, Merck, Pfizer, Threshold. M. Gordon: Research funding from Genentech and Roche for research activities which is provided to the institution. P.R. Conkling: Research funding: USOncology Research. S.J. Antonia: Honoraria: BMS, AstraZeneca, Advisory boards: Genetech, Merck Consulting: BMS, AstraZeneca Research: Medimmune Travel: BMS, AstraZeneca. B. Liu, D.S. Shames, A. Lopez-Chavez: Genentech employee. C. O'Hear: Genentech Employee. Stocker/other ownership: Genentech/Roche. Research funding from Genentech. M. Fasso: Genentech Employee and Aduro Bio Tech, Inc. All other authors have declared no conflicts of interest.