Abstract LBA57
Background
Immunotherapy plus chemotherapy is a promising treatment for first-line nsq-NSCLC. However, predictive biomarkers for this immuno-combination remain to be elucidated.
Methods
In a randomized, double-blind, phase III study evaluating the efficacy of sintilimab, an anti-PD-1 antibody, plus pemetrexed and platinum (Chemo) as first-line treatment (ORIENT-11), 397 patients with locally advanced or metastatic nsq-NSCLC were randomized (2:1 ratio) to receive either sintilimab plus Chemo (Combo) or placebo plus Chemo. The primary endpoint was progression-free survival (PFS). RNA sequencing was conducted on 248 baseline tumor biopsies (168 in Combo and 80 in Chemo).
Results
Combo group showed superiority to Chemo group in PFS (HR=0.48, 95%CI: 0.36-0.64, p<0.0001). Survival analysis showed that top 20 genes (Ranked by P-value) including ITGB2, ADAP2, MPP1, PIK3AP1, GBGT1, RAB27A, CD180, NEK6, RLN3, CD84, CASP8, DRAM1, HLA-DMB, OTULIN, HELZ, VDR, HLA-DPA1, MX2, FUCA1, MKRN1 were significantly associated with good efficacy of Combo treatment (mean HR 0.26, P<0.0001) but not Chemo treatment except for NEK6 (HR, 0.38; 95% CI, 0.14−0.50; P=0.0047). In line with this, we found that the entire signature score of MHC-II antigen presentation pathway was more significantly associated with clinical efficacy of Combo (HR, 0.51; 95% CI, 0.28-0.91; P=0.0230) than that of MHC-I (HR, 0.70; 95% CI, 0.39−1.25; P=0.2230). It was further validated that cells with MHC-II presentation capability also contributed to the longer PFS in the Combo group, e.g. macrophage (HR, 0.48; P=0.0120), activated dendritic cell (HR, 0.46; P=0.0114), immature dendritic cell (HR, 0.47; P=0.0134), or immature B cell (HR, 0.51; P=0.0245). Finally, multiplex immunohistochemistry data from 57 patients demonstrated concordance between RNA and protein expression and that higher level of CD68 protein was associated with good outcome (HR, 0.42; 95% CI, 0.12-1.54; P=0.1930).
Conclusions
Signature of MHC-II antigen presentation was significantly associated with longer PFS in patients receiving immune-combination therapy and could be served as a predictive biomarker.
Clinical trial identification
NCT03607539.
Editorial acknowledgement
Legal entity responsible for the study
Innovent Biologics, Inc.
Funding
Innovent Biologics Inc. and Eli Lilly and Company.
Disclosure
J. Sun, H. Zhou, S. Wang, W. Xu, B. Peng: Full/Part-time employment: Innovent Biologics Inc. L. Zhang: Research grant/Funding (self): Eli Lilly and Company; Research grant/Funding (self): Pfizer. All other authors have declared no conflicts of interest.
Resources from the same session
LBA56 - ORIENT-12: Sintilimab plus gemcitabine and platinum (GP) as first-line (1L) treatment for locally advanced or metastatic squamous non-small-cell lung cancer (sqNSCLC)
Presenter: Caicun Zhou
Session: Mini Oral - NSCLC, metastatic
Resources:
Abstract
Slides
Webcast
1260MO - Activity of OSE-2101 in HLA-A2+ non-small cell lung cancer (NSCLC) patients after failure to immune checkpoint inhibitors (ICI): Step 1 results of phase III ATALANTE-1 randomised trial
Presenter: Giuseppe Giaccone
Session: Mini Oral - NSCLC, metastatic
Resources:
Abstract
Slides
Webcast
LBA58 - ORR in patients receiving nivolumab plus radiotherapy in advanced non-small cell lung cancer: First results from the FORCE trial
Presenter: Farastuk Bozorgmehr
Session: Mini Oral - NSCLC, metastatic
Resources:
Abstract
Slides
Webcast
LBA59 - First-line nivolumab (NIVO) + ipilimumab (IPI) combined with 2 cycles of platinum-based chemotherapy (chemo) vs 4 cycles of chemo in advanced non-small cell lung cancer (NSCLC): Patient-reported outcomes (PROs) from CheckMate 9LA
Presenter: Martin Reck
Session: Mini Oral - NSCLC, metastatic
Resources:
Abstract
Slides
Webcast
LBA60 - ZENITH20, a multinational, multi-cohort phase II study of poziotinib in NSCLC patients with EGFR or HER2 exon 20 insertion mutations
Presenter: Mark Socinski
Session: Mini Oral - NSCLC, metastatic
Resources:
Abstract
Slides
Webcast
LBA61 - First analysis of RAIN-701: Study of tarloxotinib in patients with non-small cell lung cancer (NSCLC) EGFR Exon 20 insertion, HER2-activating mutations & other solid tumours with NRG1/ERBB gene fusions
Presenter: Stephen Liu
Session: Mini Oral - NSCLC, metastatic
Resources:
Abstract
Slides
Webcast
1261MO - Updated results from a phase I/II study of mobocertinib (TAK-788) in NSCLC with EGFR exon 20 insertions (exon20ins)
Presenter: Gregory Riely
Session: Mini Oral - NSCLC, metastatic
Resources:
Abstract
Slides
Webcast
LBA62 - Efficacy and safety of patritumab deruxtecan (U3-1402), a novel HER3 directed antibody drug conjugate, in patients (pts) with EGFR-mutated (EGFRm) NSCLC
Presenter: Helena Yu
Session: Mini Oral - NSCLC, metastatic
Resources:
Abstract
Slides
Webcast
Open & welcome
Presenter: Natasha Leighl
Session: Mini Oral - NSCLC, metastatic
Resources:
Slides
Webcast
Invited Discussant LBA56, LBA57 and 1260MO
Presenter: Natasha Leighl
Session: Mini Oral - NSCLC, metastatic
Resources:
Slides
Webcast