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Efficacy, safety and predictive biomarker results from a randomized phase II study comparing MPDL3280A vs docetaxel in 2L/3L NSCLC (POPLAR).
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
|n =||TC3 or IC3||TC2/3 or IC2/3||TC1/2/3 or IC1/2/3||TC0 and IC0||ITT|
|HRa 95% CI||0.47|
|HR 95% CI||0.56|
|ORR, % |
NR, not reached. aStratified HR for ITT and unstratified HR for subgroups.
Abstracts by Alexander I. Spira:
- Meeting: 2016 Gastrointestinal Cancers Symposium | Abstract No: 196
A phase 1, open-label, dose-escalation, multicenter study to evaluate the tolerability, safety, pharmacokinetics, and activity of ADCT-301 in patients with relapsed or refractory CD25-positive acute myeloid leukemia.Meeting: 2016 ASCO Annual Meeting | Abstract No: TPS7071
A phase 2 study of seribantumab (MM-121) in combination with docetaxel or pemetrexed versus docetaxel or pemetrexed alone in patients with heregulin positive (HRG+), locally advanced or metastatic non-small cell lung cancer (NSCLC).Meeting: 2016 ASCO Annual Meeting | Abstract No: TPS9110
Presentations by Alexander I. Spira:
Efficacy, Safety and Predictive Biomarker Results from a Randomized Phase II Study Comparing Atezolizumab (MPDL3280A) vs Docetaxel in 2L/3L NSCLC (POPLAR)Meeting: 2015 ASCO Annual Meeting Abstract No: 8010Session: Immunotherapy in Lung Cancer: A Paradigm Shift (Clinical Science Symposium)