Several key researches supported by Amoy Diagnostics were presented at WCLC 2022. The WCLC is the world’s largest meeting dedicated to lung cancer and other thoracic malignancies, attracting more than 7,000 researchers, physicians and specialists from more than 100 countries. All these research findings were led by clinical experts.

EP16.03-033

Structure-based classification of Chinese patients with non-canonical EGFR-mutant Non–Small Cell Lung Cancer

L Gu1, Y Yu1, L Shen1, S Lu, F Yao 2, C Zhu2, J Wang2, S Lu1

1.Shanghai Chest Hospital, Shanghai, China;

2.Amoy Diagnostics Co., Ltd., Xiamen, China.

BACKGROUND

Non-canonical EGFR mutations in non-small cell lung cancer (NSCLC) could be re-classified into four subtypes (Classical-like, P-loop and αC-helical compressing (PACC), T790M-like, and exon 20 loop insertions) based on unique structures as well as response to various types of tyrosine kinase inhibitors (TKIs). Since EGFR most frequently mutated in East-Asian population, it is clinically crucial to investigate the distribution of structure-based EGFR classification in Chinses NSCLCpatients.

METHODS

4692 EGFR mutant NSCLC patients with available next-generation sequencing result were collected (cohort 1). Another cohort (cohort 2) of 266 NSCLC patients with accessible EGFR testing results and time to treatment failure (TTF) for EGFR-TKI was retrospectively recruited from Department of Oncology, Shanghai Chest Hospital.

CONCLUSION

In this study, for the first time, we applied the structure-based classification approach to characterize the mutational landscape of EGFR-mutant patients in Chinese patients with NSCLC. Adopting this structure–function-based EGFR classification into clinical practice may improve the precision medicine for EGFR mutant NSCLC patients as well as benefit future drug development and clinical trial design.

EP16.03-031

Transcriptomic Heterogeneity in Non–Small Cell Lung Cancer Harboring

Different EGFR Exon 19 Del/Delins variants

L Gu1, Y Yu1, L Shen1, S Lu, F Yao 2, C Zhu2, J Wang2, S Lu1

1.Shanghai Chest Hospital, Shanghai, China;

2.Amoy Diagnostics Co., Ltd., Xiamen, China.

BACKGROUND

Exon 19 deletion (19Del) and deletion-insertion (19Delins) of epidermal growth factor receptor (EGFR) gene were common drivers in non–small cell lung cancer (NSCLC). However, it was reported that response to EGFR-TKIs displayed a variant type- dependent manner for NSCLC with EGFR 19 Del/Delins. It is of great importance to deepen the understanding of biological heterogeneity of NSCLC harboring different types of EGFR Exon 19Del/Delins.

METHODS

NGS data of 1242 patients diagnosed as advanced NSCLC with EGFR 19del/19delins variant were retrospectively reviewed. 81 patients with 1813-gene expression data(Master panel, Amoy Diagnostics Co ., Ltd)were further analyzed to compare biological difference. Gene-set enrichment analysis was conducted using the Cluster Profiler package in R 4.0.5.

RESULTS

Total of 48 different EGFR 19Del/Delins variants were identified. Total 1242 patients were divided into classic 19del subtype group (p.E746_A750del, n=759, 64.0%) and atypical mutations group (36%) including 19 del group (n=92, 7.4%) and 19 delins group (n=355, 28.6%). The atypical classical 19del group contains p.L747_T751del (76.1%), L747_S752del (15.2%), S752_I759del (7.6%) andL747_E749del (1.1%) variants. And the atypical 19delins group, L747_P753delinsS (28.7%), p.L747_A750delinsP (20.6%), p.E746_S752delinsV(12.1%)were the most frequent variants.

CONCLUSION

NSCLC with EGFR 19 Del/Delins should not be considered as a homogenous disease. NSCLC with uncommon EGFR 19Del/Delins displayed a more active adaptive immunity in tumor microenvironment, which indicated the potential vulnerability of immunotherapy.

EP16.03-032

Transcriptomic Heterogeneity in Non–Small Cell Lung with four structure-based

EGFR-mutation subgroups

L Gu1, Y Yu1, L Shen1, S Lu, F Yao 2, C Zhu2, J Wang2, S Lu1

1.Shanghai Chest Hospital, Shanghai, China;

2.Amoy Diagnostics Co., Ltd., Xiamen, China.

BACKGROUND

EGFR mutations were classified into four subtypes (Classical-like, P-loop and αC-helical compressing (PACC), T790M-like, and exon 20 loop insertions) based on unique structures as Jacqulyne previously reported (Nature, 2021). Thus, EGFR mutant non-small cell lung cancer (NSCLC) should not be considered as a heterogeneous disease. Thus, there is clearly an unmet need understanding the biology trait of NSCLC with distinct EGFR mutation subtypes.

METHODS

Total 2731 EGFR mutant NSCLC patients with available next- generation sequencing result were retrospectively reviewed. 119 patients with 1813-gene expression data were further analyzed to compare biological difference. Gene-set enrichment analysis was conducted using the Cluster Profiler package in R 4.0.5.

CONCLUSION

This study, of first time, demonstrated the heterogenous biology of NSCLC driven by distinct EGFR mutations with distinct structures at transcriptional and functional level.

EP16.01-005

Cilia-related mRNA profile predicts clinical response to PD-1 blockade in lung adenocarcinoma

G Gao1*, T Jiang1, F Zhou1, F Wu1, W Li1, A Xiong1, X Chen1, S Ren1, C Su1, T Hu2, Q Li2, C Zhu2, C Zhou1#

1.Shanghai Pulmonary Hospital, Shanghai, China

2.Amoy Diagnostics Co., Ltd., Xiamen, China.

BACKGROUND

Immune checkpoint blockades (ICBs) results improved clinical outcome and life quality in various types of malignancies. While immunotherapy does not fit for all patients. Developing appropriate biomarkers to maximize the clinical efficacy of ICBs is unmet clinical need.

METHODS

Total 45 patients with lung adenocarcinoma (LUAD) with available RNA sequencing result were divided into discovery (n=24) and validation cohort (n=21). Expression profile was compared in discovery cohort between patients with durable clinical benefit (DCB) and non- durable benefit (NDB). ROC- AUC was used to evaluate performance of constructed model for predicting response to immunotherapy in discovery and validation cohort

CONCLUSION

A Cilia risk model was constructed for the first time to predict the clinical efficacy of immunotherapy in patients with lung adenocarcinoma.