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Hai Tran
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P1.04 - Immuno-oncology (ID 164)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Immuno-oncology
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.04-11 - Depicting the Intra-Tumoral Viral and Microbial Landscape of Localized NSCLC Using Standard Next Generation Sequencing Data (ID 1126)
09:45 - 18:00 | Author(s): Hai Tran
- Abstract
Background
Studies from our group and others have shown that bacteria and viruses present in the tumor may impact therapeutic responses. In the specific context of non-small cell lung cancer (NSCLC), intra-tumoral viral DNA and bacteria have been reported previously to be linked to therapeutic outcomes. However, the interplay between intra-tumoral microorganisms and the host immune response in NSCLC remains unknown. Moreover, the prognostic and predictive therapeutic value of localized NSCLC-specific microbial composition has yet to be defined.
Method
RNA-sequencing (RNA-seq) (n=82) and whole exome sequencing (WES) (n=80) was performed on surgically resected (pTNM I-III) tumors from lung cancer patients enrolled in the ImmunogenomiC prOfiling of NSCLC (ICON) project. Intra-tumoral bacteria, viruses and fungi were queried with MetaPhlAn2, a bioinformatical analysis pipeline which employs unique clade-specific marker genes, using reads from RNA-seq and WES that did not map to the human genome/transcriptome. Generated data were correlated to patients’ clinicopathologic parameters as well as immune profiling using previously validated multiplex IHC panels based on Vectra 3.0™ multispectral microscopy IHC panels and image analysis (InForm™ 2.2.1 software).
Result
Our analyses revealed that 18.29% (n=15/82) of tumors contained bacterial signatures. The most frequent bacterial signature was related to Escherichia (n=9/15). Moreover, 6.49% (n= 5/77) of tumors had evidence of human viral signatures, including the Epstein-Barr virus (n=1/5). No tumors contained fungal signatures. Preliminary clinicopathologic analyses suggested that patients whose tumors harbor bacterial signatures had a trend towards decreased overall survival (p=0.12). Tumors from former smokers were also more likely to contain bacterial signatures (p=0.11). Preliminary multiplex immune cell IHC analyses did not highlight statistically significant associations with the presence of intra-tumoral bacteria.
Conclusion
Our results suggest that a significant proportion of localized NSCLC tumors may harbor components of the human microbiome. Further studies using larger cohorts and dedicated intra-tumoral microbiome and virome methodologies will be needed to better define these findings and to delineate associations with the local immune infiltrate.
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P2.14 - Targeted Therapy (ID 183)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Targeted Therapy
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.14-24 - An Open-Label Randomized Phase II Study of Combining Osimertinib With and Without Ramucirumab in TKI-Naïve EGFR-Mutant Metastatic NSCLC (ID 851)
10:15 - 18:15 | Author(s): Hai Tran
- Abstract
Background
Osimertinib, a third-generation EGFR inhibitor, has become the first-line therapy for patients with metastatic EGFR-mutant NSCLCs since 2018. Osimertinib is well-tolerated, therefore, it opens opportunities to be combined with other therapeutic agents to enhance the treatment outcome. In preclinical models, it has been shown that upregulated VEGF signaling mediates acquired resistance to EGFR therapies. In xenograft models, combination of anti-VEGF medications with EGFR inhibitors were significantly more effective than erlotinib or gefitinib alone. Ramucirumab, a monoclonal antibody targeting VEGF receptor 2, is approved with docetaxel in as second line treatment for NSCLCs. In clinical trial evaluations, the phase 3 RELAY trial (NCT02411448) studying ramucirumab plus erlotinib in patients with metastatic untreated EGFR-mutant NSCLC patients showed a statistically significant improvement in progression-free survival in the combination group compared to erlotinib alone. A phase I study of osimertinib with ramucirumab (NCT02789345) demonstrated safety and feasibility of this combination. With strong preclinical and clinical evidence showing dual inhibition of VEGF/EGFR signaling prolongs progression-free survival for EGFR-mutant lung cancers, and demonstrated safety, we are conducting a phase 2 trial to evaluate the osimertinib ramucirumab combination’s efficacy in treatment-naïve EGFR-mutant NSCLC.
Method
The OSI+RAM trial is a randomized phase 2 study with the primary endpoint being progression-free survival in osi+ram group as compared to osimertinib monotherapy group. The major inclusion criteria include patients with metastatic NSCLC harboring EGFR mutations (L858R/Exon 19 del). The major exclusion criteria include prior anti-EGFR or anti-VEGF treatments. Patients with stable CNS metastasis are allowed. Based on the results from erlotinib bevacizumab (NEJ026) study, we expect an improvement of PFS from 18.9 months to 29.7 months, corresponding to a hazard ratio of 0.65. The trial plans to enroll total of 150 patients, with 100 allocating to osi+ram arm and 50 to osimertinib monotherapy. Total of 9 study sites in the USA are planned. Hoosier Cancer Research Network will facilitate the execution of the trial. The trial protocol has received IND exemption from US FDA and has been approved by IRB at MD Anderson Cancer Center. The first subject is expected to be enrolled in May 2019. A planned interim analysis will be performed after the first 75 subjects are enrolled. NCT03909334.
Result
Section not applicable
Conclusion
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