Abstract 5014
Background
Responses in NSCLC to agents targeting the PD-1/PD-L1 axis are correlated with PD-L1 expression by immunohistochemistry (IHC), tumor mutational burden (TMB), interferon associated mRNA Expression Profile (GEP) and the absence of liver metastases. Pegilodecakin (AM0010) is a pegylated recombinant human interleukin-10 that stimulates activation, survival and clonal expansion of intra-tumoral, tumor antigen specific CD8+ T cells. Pegilodecakin also up-regulates IFNγ and the expression of MHC, which enables tumor antigen presentation in neoplasias of low mutational burden and promotes immunosurveillance by expanding effector memory T cells (Mumm et al. 2010, 2011). Finally, pegilodecakin reduces tumor inflammatory processes such as angiogenesis and and metastatic dissemination (Oft 2017), the off-target auto-immune side effects of immunotherapy and the inflammatory-related side effects of some chemotherapies.
Methods
In a 353 patient phase 1/1b dose escalation and expansion study, 34 pretreated NSCLC subjects received pegilodecakin with pembrolizumab or nivolumab. Responses were assessed by irRC. PD-L1 was tested with the 22C3 IHC assay, TMB by whole exome sequencing and pre-treatment GEP by Nanostring.
Results
Conclusions
Pegilodecakin when added to anti-PD-1 therapy in advanced NSCLC patients was associated with response rates and durability of benefit greater than has been seen with anti-PD-1 alone. Responses were seen in settings in which anti-PD-1 therapy has demonstrated limited benefit, such as absent PD-L1 expression, low TMB and/or the presence of liver metastasis. These preliminary findings support further studies of pegilodecakin with anti-PD-1 therapies.Table: 1144P
| Pegilodecakin1 | N | Prior Therapies | ORR | DCR | mPFS | mOS | irAE11 | irAE11 |
|---|---|---|---|---|---|---|---|---|
| Regimen | E (ITT)10 | Median (Range) | % | % | mos | mos | All Grades (%) | Grades 3 & 4 (%) |
| Plus Pembrolizumab2 | 5 (5) | 2 (0-5) | 40.0 | 100 | 11.0 | 32.2 | ||
| Plus Nivolumab3 | 22 (29) | 2 (0-5) | 41.0 | 82.0 | 7.4 | NR | ||
| Pooled Plus Anti-PD-14 | 27 (34) | 2 (0-5) | 41.0 | 85.0 | 8.9 | NR | 14.7 | 5.9 |
| Sub-Populations | N | |||||||
| PD-L1 High5 | 5 | 80.0 | 100 | 10.7 | NR | |||
| PD-L1 Low6 | 3 | 67.0 | 91.6 | 8.9 | NR | |||
| PD-L1 Negative7 | 12 | 33.0 | 67.0 | 5.7 | NR | |||
| TMB High8 | 2 | 50.0 | 50.0 | 7.2 | 14.0 | |||
| TMB Low9 | 8 | 63.0 | 100 | 10.3 | NR | |||
| Liver Mets | 8 | 63.0 | 75.0 | 9.8 | 12.3 |
10-20µg/kg QD SC;
22mg/kg, q3wk IV;
33mg/kg, q2wk IV;
4pembrolizumab and nivolumab cohorts combined;
5PD-L1 >50%;
6PD-L1 1%-49%;
7PD-L1 <1%;
8TMB High (tumor mutational burden high) >243 mut/exome;
9TMB Low (tumor mutational burden low) <243 mut/exome;
10E (evaluable - baseline tumor assessment + >1 post-baseline assessments, and no major protocol deviations); ITT (intent to treat);
11irAE - Immune-Related Adverse Events (e.g. pneumonitis, adrenal insufficiency, thyroiditis, hypothyroiditis, hypophysitis, mucositis/stomatis, colitis, hepatitis, cholangitis, polyarthritis, myasthenia gravis, optic neuritis); Data cut on 05.01.18; Median follow-up for pembrolizumab cohort 37.3 months (35.9-39.1 months); Median follow-up for nivolumab cohort 23.2 months (9.1-32.0 months)
Clinical trial identification
NCT02009449.
Legal entity responsible for the study
ARMO BioSciences.
Funding
ARMO BioSciences.
Editorial Acknowledgement
Disclosure
A. Hung, M. Oft, J. Leveque: Employee: ARMO BioSciences. All other authors have declared no conflicts of interest.
Resources from the same session
3816 - A prediction panel with DNA methylation biomarkers for lung adenocarcinoma
Presenter: Nan Shen
Session: Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research
Resources:
Abstract
5242 - Novel genomic classifier for early stage colorectal cancer patients
Presenter: Elisabeth Letellier
Session: Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research
Resources:
Abstract
5404 - Baseline Blood Immune Profiling to Predict Response to antiPD-1 in Patients with Advanced Non-Small Cell Lung Cancer
Presenter: Emanuela Romano
Session: Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research
Resources:
Abstract
5462 - Evaluation of clinicopathological and molecular criterias for screening of exonucleasic domain POLE (edPOLE) mutated patients in proficient Mismatch Repair (pMMR) colorectal and endometrial cancers.
Presenter: Justine Cohen
Session: Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research
Resources:
Abstract
5465 - Immune prognostic index (IPI) and Hyper-Progressive disease (HPD) in patients (pts) exposed to targeted agents (TAs) in Phase 1 trials (Ph1T): can lessons from immune checkpoint inhibitors (ICIs) be translated to other scenarios?
Presenter: Ignacio Matos Garcia
Session: Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research
Resources:
Abstract
5742 - Combination of baseline LDH, performance status and age to identify solid tumor patients with higher probability of response to anti-PD1 and PDL1 monoclonal antibodies
Presenter: Maria Silvia Cona
Session: Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research
Resources:
Abstract
5790 - Effects of concomitant genetic alterations on cancer patient overall survival
Presenter: Yu Wang
Session: Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research
Resources:
Abstract
5144 - Circulating Exosomal Integrin _v_5 Predicts Liver Metastasis and Prognosis in Human Colorectal Cancer
Presenter: Dake Chu
Session: Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research
Resources:
Abstract
5149 - Circulating and tumor-associated caspase-4: a novel diagnostic and prognostic biomarker for Non-Small Cell Lung Cancer patients?
Presenter: Rosalinda Sorrentino
Session: Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research
Resources:
Abstract
5673 - Smokers and COPD patients have high circulating caspase-4 levels: is it an alarm?
Presenter: Michela Terlizzi
Session: Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research
Resources:
Abstract