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

Abstract

8010 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, mo NR 11.1 13 7.4 NR 9.1 9.7 9.7 11.4 9.5 HRa 95% CI 0.47 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, mo 9.7 3.9 4.0 2.8 3.3 3.0 1.9 4.1 2.8 3.4 HR 95% CI 0.56 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) 38 13 22 15 18 18 8 10 15 15 NR, not reached. aStratified HR for ITT and unstratified HR for subgroups.

Keywords

Affiliated Institutions

• KU Leuven BE
• NRG Oncology US
• Virginia Cancer Specialists US
• Hôpital Larrey FR
• Kaiser Permanente US
• Samsung Medical Center KR
• Sungkyunkwan University KR
• Roche (Switzerland) CH

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