Abstract 4614
Background
Response to checkpoint inhibitors (CI) is governed by the tumor immune environment and understanding this immune contexture can predict response. Therapeutic intervention can change this environment even in the absence of clinical response. Patients failing initial immunotherapy may respond to a second line of CI; however, these cohorts show lower overall response rates (ORR). This study identifies transcriptional signatures associated with response to first- and second-line CI monotherapy in melanoma.
Methods
CI-naïve or ipilimumab-refractory patients were treated with ipilimumab, nivolumab or pembrolizumab at the Instituto Nazionale Tumori and clinical response was evaluated by irRECIST 1.1 criteria. Pretreatment tumor biopsies (n = 82) from metastatic lesions were collected and RNA was profiled with the NanoString® IO360 gene expression panel.
Results
Compared to CI-naïve cohorts, ipilimumab-refractory cohorts had reduced ORR to nivolumab (naïve: 35%, n = 6; refractory: 20%, n = 10) or pembrolizumab (naive: 67%, n = 6; refractory: 20%, n = 10) with multiple genes differentially expressed between groups. The Tumor Inflammation Signature, an investigational 18 gene signature of suppressed adaptive immune response enriching for pembrolizumab response, was higher in responders versus non-responders in first-line (log2 fold change: 1.56, p = 0.21), but not second-line pembrolizumab (log2 fold change: 0.41, p = 0.60). First-line pembrolizumab responders had elevated MHC2 (log2 fold change: 1.35, p = 0.02) and B cell (log2 fold change: 2.14, p = 0.02) signatures. Upon stratifying the CI-naïve cohort between no prior treatment versus prior targeted/chemotherapy, the latter had increased immune expression suggesting these therapies prime the tumor immune environment.
Conclusions
Correlating patterns of tumor gene expression with clinical response can lead to the development of biomarkers enriching for CI response in both first-line and CI-refractory patients. Utilization of a clinical grade platform such as the NanoString nCounter® may speed the development of diagnostic assays used to predict and monitor patient response to immunotherapy.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
NanoString Technologies.
Disclosure
S. Ong: Full / Part-time employment: NanoString Technologies. S. Warren: Shareholder / Stockholder / Stock options, Full / Part-time employment: NanoString Technologies. A. Cesano: Shareholder / Stockholder / Stock options, Full / Part-time employment: NanoString Technologies. J.M. Beechem: Shareholder / Stockholder / Stock options, Full / Part-time employment: NanoString Technologies. P.A. Ascierto: Advisory / Consultancy: Amgen; Advisory / Consultancy: Array; Advisory / Consultancy: BMS; Advisory / Consultancy: Incyte; Advisory / Consultancy: Immunocore; Advisory / Consultancy: MedImmune; Advisory / Consultancy: IDERA; Advisory / Consultancy: Genmab; Advisory / Consultancy: Merck; Advisory / Consultancy: Roche; Advisory / Consultancy: Genentech; Advisory / Consultancy: Sandoz; Advisory / Consultancy: Syndax; Advisory / Consultancy: Sun Pharma; Advisory / Consultancy: Ultimovacs; Advisory / Consultancy: Pierre Fabre; Advisory / Consultancy: Novartis. All other authors have declared no conflicts of interest.
Resources from the same session
5760 - Landscape of PD-L1 expression status in Chinese solid tumor patients.
Presenter: Yi Zhong
Session: Poster Display session 3
Resources:
Abstract
3733 - Anti-cancer and immunomodulatory effects of cobimetinib in triple negative breast cancer
Presenter: Chun-Yu Liu
Session: Poster Display session 3
Resources:
Abstract
4426 - Differential expression of immunoregulatory molecules and highly-associated cancer genes may provide novel insights into strategic trial design for therapeutics
Presenter: Jacob Adashek
Session: Poster Display session 3
Resources:
Abstract
2752 - Insights into the Tumor Immune Microenvironment using Tissue Phenomics to Drive Cancer Immunotherapy
Presenter: Martin Groher
Session: Poster Display session 3
Resources:
Abstract
5713 - Immune competent somatic mosaic model of colorectal cancer
Presenter: Stefania Napolitano
Session: Poster Display session 3
Resources:
Abstract
1898 - Genomic correlates of response to anti-PDL1 Atezolizumab in non-small-cell lung cancer OAK and POPLAR trials
Presenter: Hari Singhal
Session: Poster Display session 3
Resources:
Abstract
3246 - Erdafitinib (erda) versus available therapies in advanced urothelial cancer: A matching adjusted indirect comparison
Presenter: Yohann Loriot
Session: Poster Display session 3
Resources:
Abstract
3311 - High level of activity of Nivolumab anti-PD-1 immunotherapy and favorable outcome in metastatic/refractory MSI-H non-colorectal cancer: Results of the MSI cohort from the French AcSé program
Presenter: Christophe Tournigand
Session: Poster Display session 3
Resources:
Abstract
2314 - TP53 and ATM Co-mutation Predicts Response to Immune Checkpoint Inhibitors in Non-Small Cell Lung Cancer
Presenter: Yu Chen
Session: Poster Display session 3
Resources:
Abstract
4692 - Immune cell biomarkers on neo-adjuvant chemo-immunotherapy treatment for resectable stage IIIA NSCLC patients
Presenter: Raquel Laza-Briviesca
Session: Poster Display session 3
Resources:
Abstract