150315-156

Efficacy, safety and predictive biomarker results from a randomized phase II study comparing MPDL3280A vs docetaxel in 2L/3L NSCLC (POPLAR).

Category: 
Lung Cancer—Non-Small Cell Metastatic
Session Type and Session Title: 
Clinical Science Symposium, Immunotherapy in Lung Cancer: A Paradigm Shift
Abstract Number: 

8010

Citation: 
J Clin Oncol 33, 2015 (suppl; abstr 8010)
Author(s): 
Alexander I. Spira, Keunchil Park, Julien Mazières, Johan F. Vansteenkiste, Achim Rittmeyer, Marcus Ballinger, Daniel Waterkamp, Marcin Kowanetz, Ahmad Mokatrin, Louis Fehrenbacher; Virginia Cancer Specialists Research Institute, US Oncology Research, Fairfax, VA; Division of Hematology & Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea; Hôpital Larrey CHU Toulouse, Toulouse, France; University Hospital KU Leuven, Leuven, Belgium; Lungenfachklinik Immenhausen, Kassal, Germany; Genentech, Inc., South San Francisco, CA; F. Hoffmann-La Roche Ltd., Basel, Switzerland; NRG Oncology/NSABP, and Kaiser Permanente Northern California, Novato, CA

Abstract Disclosures

Abstract: 

Background: MPDL3280A (anti-PDL1) has demonstrated promising response rates in NSCLC that correlated with PD-L1 expression on tumor-infiltrating immune cells (IC) and/or tumor cells (TC) (Horn et al, ASCO 2015). Methods: Previously treatedNSCLC patients (pts) were stratified by PD-L1 IC status, histology and prior lines of therapy and randomized to 1200 mg IV q3w MPDL3280A (M) or 75 mg/m2 IV q3w docetaxel (D). PD-L1 expression was centrally evaluated by IHC using the SP142 antibody assay. Pts were scored as TC0, 1, 2 or 3 and IC0, 1, 2 or 3. The primary endpoint was OS (data cutoff, January 30, 2015; median follow-up, 12 mo). Results: 287 pts were randomized. In this interim analysis, improved efficacy was observed with increasing PD-L1 expression (e.g., OS HR, 0.47; PFS HR, 0.56 and ORR, 38% vs 13% in TC3 or IC3 pts), while pts with the lowest PD-L1 levels (TC0 and IC0) did not appear to benefit from M (OS HR, 1.22; see table). ITT OS HR was 0.78. Safety was evaluable for 277 pts. Despite a longer median treatment duration for M (3.6 vs 2.1 mo for D), fewer pts receiving M (43%) vs D (56%) experienced Gr ≥ 3 AEs. There were no unexpected toxicities. Conclusions: This is the first randomized study in non-squamous and squamous NSCLC to demonstrate that inhibition of the PD-L1/PD-1 pathway may lead to improved survival. Furthermore, these data showed that PD-L1 biomarker selection, using a highly sensitive and specific IHC assay measuring PD-L1 on both TC and IC, can identify both pts most likely to derive improved OS, PFS and ORR and pts unlikely to benefit vs standard of care (NCT01903993). A second randomized study in this pt population is ongoing. Clinical trial information: NCT01903993

Efficacy.

n =TC3 or IC3
TC2/3 or IC2/3
TC1/2/3 or IC1/2/3
TC0 and IC0
ITT
M
24
D
23
M
50
D
55
M
93
D
102
M
51
D
41
M
144
D
143
OS
Median, moNR11.1137.4NR9.19.79.711.49.5
HRa 95% CI0.47
0.20-1.11
0.56
0.33-0.95
0.63
0.42-0.95
1.22
0.69-2.14
0.78
0.59-1.03
PFS
Median, mo9.73.94.02.83.33.01.94.12.83.4
HR 95% CI0.56
0.28-1.11
0.70
0.45-1.08
0.87
0.63-1.20
1.15
0.72-1.82
0.96
0.76-1.20
ORR, %
(confirmed)
3813221518188101515

NR, not reached. aStratified HR for ITT and unstratified HR for subgroups.