TPS8675 Background: Despite advances in treatment of NSCLC with EGFR classical mutations, no universally accepted standard-of-care treatment exists for patients with EGFR uncommon mutations including PACC mutations. Treatment options include EGFR tyrosine kinase inhibitors (TKIs) (osimertinib, afatinib), chemotherapy, or other targeted therapies (amivantamab for exon 20 insertion mutations). EGFR PACC mutations comprise approximately 12.5% of all NSCLC EGFR mutations (Robichaux et al 2021, Nilsson et al 2024). Firmonertinib is a once daily oral, highly brain penetrant, broadly active mutant-selective EGFR inhibitor that targets classical and uncommon mutations (Musib et al., NACLC 2022). In the phase 1b FURMO-002 study (FURTHER), first-line locally advanced or metastatic EGFR PACC mutation NSCLC patients treated with firmonertinib 240 mg daily achieved a confirmed ORR of 68.2%, best ORR of 81.8%, disease control rate (DCR) of 100%, and median progression-free survival (mPFS) of 16.5 months by blinded independent central review (BICR) (Le et al., WCLC 2025). Firmonertinib was generally well-tolerated with manageable EGFR TKI-associated adverse events. Methods: ALPACCA (FURMO-006; NCT07185997) is a global, phase 3, randomized, open-label study investigating firmonertinib vs investigator’s choice of osimertinib or afatinib. Eligible patients have locally advanced or metastatic NSCLC with EGFR PACC mutations. Key inclusion criteria include documented presence of EGFR PACC mutation and measurable disease per RECIST v1.1. Patients with asymptomatic CNS metastases are allowed. Key exclusion criteria include prior systemic anticancer therapy in the locally advanced or metastatic setting or any prior EGFR TKI therapy. Approximately 480 patients will be randomized 1:1 to receive firmonertinib 240 mg daily or investigator’s choice of osimertinib 80 mg daily or afatinib 40 mg daily. Primary endpoints are PFS and ORR per RECIST v1.1 by BICR. Key secondary endpoints include OS, investigator assessed PFS and ORR, and safety and tolerability. Enrollment is ongoing. Clinical trial information: NCT07185997 .

Background While immune checkpoint inhibitors (ICIs) are adopted as standard therapy in non-small cell lung cancer (NSCLC) patients, factors that influence variable prognosis still remain elusive. Therefore, a deeper understanding is needed of how germline variants regulate the transcriptomes of circulating immune cells in metastasis, and ultimately influence immunotherapy outcomes. Methods We collected peripheral blood mononuclear cells (PBMCs) from 73 ICI-treated NSCLC patients, conducted single-cell RNA sequencing, and called germline variants via SNP microarray. Determination of expression quantitative trait loci (eQTL) allows elucidating genetic interactions between germline variants and gene expression. Utilizing aggregation-based eQTL mapping and network analysis across eight blood cell types, we sought cell-type-specific and ICI-prognosis-dependent gene regulatory signatures. Results Our sc-eQTL analysis identified 3,616 blood- and 702 lung-cancer-specific eGenes across eight major clusters and treatment conditions, highlighting involvement of immune-related pathways. Network analysis revealed TBX21-EOMES regulons activity in CD8+ T cells and the enrichment of eQTLs in higher-centrality genes as predictive factors of ICI response. Conclusions Our findings suggest that in the circulating immune cells of NSCLC patients, transcriptomic regulation differs in a cell type- and treatment-specific manner. They further highlight the role of eQTL loci as broad controllers of ICI-prognosis-predicting gene networks. The predictive networks and identification of eQTL contributions can lead to deeper understanding and personalized ICI therapy response prediction based on germline variants. ### Competing Interest Statement The authors have declared no competing interest. * ICI : Immune checkpoint inhibitor NSCLC : Non-small cell lung cancer TSS : Transcriptional start site PBMC : Peripheral blood mononuclear cell sc-eQTL : Single-cell expression quantitative trait loci GWAS : Genome-wide association study GTEx : Genotype-Tissue Expression PR : Partial response PD : Progressive disease SD : Stable diseasee PFS : Progression-free survival OS : Overall survival cCRE : Candidate cis-regulatory element VEP : Variant effect predictor MSigDB : Molecular Signatures Database GSEA : Gene set enrichment analysis WGCNA : Weighted correlation network analysis SCENIC : Single-cell regulatory network inference and clustering GRN : Gene regulatory network HNSCC : Head and neck squamous cell carcinoma

Abstract Background: Treatment of lung cancer has changed dramatically with the use of immune checkpoint inhibitors (ICI). Nevertheless, most patients underwent drug resistance even though they initially showed a response to ICI, and there is an unmet need to delineate the mechanism. Method: We analyzed RNA sequencing data of paired pre- and post-ICI samples from 31 NSCLC patients. Among them, we identified 17 patients who underwent acquired resistance (AR) who initially showed partial or complete response or stable disease lasting more than six months, and the remaining 14 patients who showed primary resistance (PR) to ICI. The analysis was performed using a tumor microenvironment (TME) classifier, classifying immune-enriched [IE], immune-enriched and fibrotic [IE/F], fibrotic [F] and immune-desert [D] subtype, and CIBERSORTx, the immune cell deconvolutional analysis tool. Results: Most patients with AR were initially classified as IE or IE/F subtypes (N=12, 70.6%), but six out of 14 with PR (42.8%) showed IE or IE/F subtypes. Among 12 patients with initial IE or IE/F subtypes, seven (58.3%) patients turned into the D subtype after AR to ICI. Most patients initially classified as D or F subtypes (N=5, 29.4%) maintained their subtypes (N=4, 80%) after AR.When assessing the pre-ICI samples, memory B cell was enriched, and M2 macrophage and regulatory T cell were depleted in AR patients compared to PR. The memory B cell and resting memory CD4+T cell decreased, and M2 macrophage increased after AR to ICI. These immune cell composition changes were not observed in PR patients. Conclusions: We observed differences in TME phenotype and immune cell composition before ICI between AR & PR patients. The TME change from immune-enriched to desert and cell composition change of increased M2 macrophages and decreased memory B and resting CD4+ T cells after AR to ICI could be significant mechanisms of AR to ICI. Citation Format: Cheol Yong Joe, Yeong Hak Bang, Sehhoon Park, Hyun Ae Jung, Jong-Mu Sun, Yoon-La Choi, Jin Seok Ahn, Myung-Ju Ahn, Se-Hoon Lee. Comprehensive transcriptomic analysis of acquired resistance after immune-checkpoint inhibitors in non-small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6839.

Abstract Background: Programmed cell death ligand 1 (PD-L1) expression alone has limited predictive value for pembrolizumab plus 5-fluorouracil and platinum (PFP) therapy in recurrent or metastatic head and neck squamous cell carcinoma (HNSCC). An artificial intelligence (AI)-powered spatial tumor-infiltrating lymphocyte (TIL) analyzer may provide independent prognostic information. Methods: This study included 63 patients with locally incurable HNSCC who received first-line PFP at Samsung Medical Center. Patients were classified into inflamed phenotype (IP) or non-inflamed phenotype (NIP) based on the 5% proportion threshold of inflamed 1 mm2-sized grids over total grids within hematoxylin and eosin-stained whole-slide images (WSIs) analyzed using Lunit SCOPE IO. We evaluated the prognostic value of inflamed status and densities of intratumoral TILs (iTILs), stromal TILs (sTILs), and tumor microenvironment TILs (tTILs). Results: Patients were predominantly male (78%). The median age at PFP initiation was 57 years. The most common primary tumor site was oral cavity (49.2%), followed by oropharynx (16%) and hypopharynx (10%). Of the 37 patients with available PD-L1 combined positive score (CPS), 2 (5%), 23 (62%), and 12 (32%) had CPS values of <1, 1-19, and ≥20, respectively. The overall response rate was 54%, with 67% in the CPS ≥20 subgroup and 48% in the CPS <20 subgroup. The median progression-free survival (PFS) was 7.2 months, with 10.8 months for patients with CPS ≥20 and 5.5 months for patients with CPS <20. The median overall survival (OS) was 18.6 months. Among 62 patients with available WSIs, 47 (74%) and 15 (26%) patients were categorized as having an IP and NIP, respectively. Oral cavity cancer was enriched with IP (57.4% of all IP cases vs 26.7% of all NIP cases), while all four paranasal sinus tumors had NIP. The overall response rate was 57% in the IP group and 44% in the NIP group. Patients with IP had significantly longer PFS and OS than patients with NIP, both in unadjusted (hazard ratio [HR] for PFS, 0.4; 95% confidence interval [CI], 0.21-0.78; P = 0.007; HR for OS, 0.43; 95% CI, 0.2-0.95; P = 0.036) and PD-L1 CPS-adjusted analyses (HR for PFS, 0.41; 95% CI, 0.21-0.79; P = 0.008; HR for OS, 0.4; 95% CI, 0.18-0.89; P = 0.025). High densities (≥25th percentile) of iTILs, sTILs, and tTILs were all significantly associated with prolonged PFS after CPS adjustment (P = 0.001, 0.001, and 0.012). High density of iTILs was also significantly associated with improved OS (P = 0.001 after CPS adjustment), while there was no significant association between OS and high density of sTILs or tTILs (0.077 and 0.085, respectively, after CPS adjustment). Conclusion: An AI-driven spatial TIL analyzer might serve as a simple and independent prognostic biomarker in HNSCC patients receiving pembrolizumab plus chemotherapy. Citation Format: Sehhoon Park, Junghoon Shin, Chan-Young Ock, Chang Ho Ahn, Hyun Ae Jung, Se-Hoon Lee, Myung-Ju Ahn. Artificial intelligence-powered spatial analysis of tumor-infiltrating lymphocytes as a prognostic biomarker for pembrolizumab plus chemotherapy in recurrent or metastatic head and neck squamous cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7658.

Abstract Introduction: In recent data of ADAURA study, adjuvant osimertinib demonstrated clinically significant improvement in overall survival in completely resected stage IB-IIIA with epidermal growth factor receptor (EGFR)-mutated NSCLC. Among 205 patients who experienced recurrence in the placebo arm, 89.8% of patients received subsequential treatment and 79.0% of patients in the placebo arm received EGFR-TKI after recurrence. Methods: This study included patients with completely resected EGFR-mutated NSCLC who confirmed to pathologic stage II-IIIA between November 2015 and February 2019 at Samsung Medical Center (SMC data). They did not receive adjuvant EGFR-TKI. To compare overall survival between the SMC data and the ADAURA study, the individual patient data (IPD) approach was applied. We assessed the overall survival of individual patient data from real-world experience in comparison to the ADAURA study. Results: A total of 547 patients were included in this study, with 51.0% at stage IB, 23.8% at stage II, and 25.2% at stage IIIA. The median follow-up duration was 71.4 months (range 1-92). At the time of data lock, 241 patients experienced recurrence in the SMC data. Among them, 230 patients (95.4%) received subsequent treatment, and 214 patients (88.8%) received EGFR-TKI after recurrence. In the stage IB and II, there was no difference of overall survival between the SMC data (reference) and the osimertinib arm of the ADAURA study (HR=0.83, 95% CI, 0.36-1.90, p=0.66 in stage IB; HR=1.08, 95% CI, 0.58-2.03, p=0.81 in stage II). However, in the stage IIIA, the 5-year survival rate was 68% in the SMC data and 85% in the osimertinib arm of the ADAURA study (HR=0.42, 95% CI, 0.24-0.73, p<0.01). In the stage IB-IIIA, the 5-year survival rate was 85% in the SMC data (reference), 78% (HR=1.68, 95% CI, 1.25-2.25, p<0.01) in the placebo arm of the ADAURA study, and 88% (HR=0.81, 95% CI, 0.56-1.16, p=0.24) in the osimertinib arm of the ADAURA study. In the stage II-IIIA, the 5-year survival rate was 77% in the SMC data (reference), 73% (HR=1.29, 95% CI, 0.92-1.82, p=0.14) in the placebo arm of the ADAURA study, and 85% (HR=0.62, 95% CI, 0.41-0.93, p= 0.02) in the osimertinib arm of the ADAURA study. Conclusions: In this study, the majority of patients received EGFR-TKIs after recurrence. The 5-year overall survival in the real-world data demonstrated superiority over the placebo arm of the ADAURA study. In stage IB and II disease, there was no significant difference between the SMC data and the osimertinib arm of the ADAURA study. Consequently, patients with pathologic stage IIIA are considered strong candidates for adjuvant osimertinib. Citation Format: Hyun Ae Jung, Junho Lee, Boram Park, Sehhoon Park, Jong-Mu Sun, Se-Hoon Lee, Jin Seok Ahn, Myung-Ju Ahn. Comparison of individual patient data from real-world experience with the ADAURA study for resected stage IB-IIIA EGFR-mutated non-small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3830.

Abstract Background: The APOBEC family of zinc-coordinating enzymes converts cytosines to uracils in single-strand DNA. APOBEC plays a crucial role in the mutation process of non-small cell lung cancer (NSCLC) and is essential for both adaptive and innate immune responses. This study aims to evaluate the role of the APOBEC mutation signature in early-stage non-small cell lung cancer (NSCLC). Methods: We conducted whole-exome sequencing and whole-transcriptome sequencing using fresh tissue or formalin-fixed paraffin-embedded samples from 100 patients diagnosed with pathologic stage II-IIIA non-squamous NSCLC, all of whom underwent complete resection between January 2014 and December 2020 at Samsung Medical Center. This study aimed to assess the impact of APOBEC enrichment on disease-free survival (DFS), progression-free survival (PFS) of EGFR-TKI, and overall survival following recurrence. Results: Median follow-up duration was 58.2 months (range, 11.3-141.1). Of the patients, 74% were never-smokers, and 52% had stage III disease. Among the 100 patients, 18 (18%) exhibited APOBEC enrichment (≥ 2). The median RFS was 25.2 months (95% CI, 17.3-33.2). Notably, APOBEC enrichment did not show a significant association with DFS (P=0.14). Among the 76 patients who experienced radiological recurrence, 69 received EGFR-TKI as first-line treatment. The median PFS for EGFR-TKI was 22.9 months (95% CI, 13.0-32.8). However, within this group, patients with APOBEC enrichment showed a shorter PFS compared to those without APOBEC enrichment (8.1 months vs. 24.6 months, P=0.014). In multivariate analysis, poor PFS of EGFR-TKI was associated with the type of EGFR mutation (L858R vs. exon 19 deletion, HR=1.9, P=0.04), TP53 mutation (mutation vs. wild type, HR=2.1, P=0.03), and APOBEC enrichment (≥ 2 vs. <2, HR=2.2, P=0.02). Overall survival from the starting EGFR-TKI was 61.1 months and 21.7 months for patients with APOBEC enrichment or patients without APOBEC enrichment, respectively (P=0.027). Conclusions: APOBEC mutation signature may be presented at initial diagnosis of early-stage EGFR mutant NSCLC and it was associated with poor PFS of EGFR-TKI and overall survival. Citation Format: Hyun Ae Jung, Jinyeong Lim, Yoon-La Choi, Sehhoon Park, Jong-Mu Sun, Myung-Ju Ahn, Se-Hoon Lee. The role of APOBEC in early stage-EGFR mutant non-small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2503.

ALK and integrin β3 show strong correlation in expression in ALK-rearranged NSCLC patient cases and in vitro

Functional role and regulation of integrin β3 in ALK-rearranged cell lines

Sequence of siRNAs and primers

Clinical characteristics of ALK-rearranged and ALK-negative NSCLC patients

Combination therapy of ALK and β3 inhibitors shows promising results in vivo and in ALK-rearranged NSCLC

Supplementary Data from Clinical, Pathologic, and Molecular Prognostic Factors in Patients with Early-Stage EGFR-Mutant NSCLC

2533 Background: Patients with EGFR mutant NSCLC who progress on or after small molecule EGFR inhibitors have only limited treatment options. AFM24 is a tetravalent, bispecific innate cell engager that binds EGFR on solid tumor cells and CD16A on NK cells to redirect and enhance antitumor antibody-dependent cellular cytotoxicity, thus acting independently of the EGFR downstream signaling pathway and EGFR expression levels. The Phase 1 dose escalation phase of the presented study (NCT04259450) established the recommended Phase 2 dose of AFM24 monotherapy at 480 mg based on tolerability, receptor occupancy, and pharmacokinetics (PK). Correlative science data revealed an activation and enrichment of immune cells in the tumor microenvironment. Methods: The Phase 2a expansion phase is evaluating 480 mg AFM24 in patients with EGFR mutant NSCLC, relapsed or refractory to ≥1 prior lines of therapy; EGFR-positivity is defined as positive staining for EGFR in ≥1% of tumor cells per local immunohistochemistry assay. The study follows Simon’s two-stage design. The primary endpoint is overall response rate per local RECIST v1.1; secondary endpoints include safety, PK, and immunogenicity. Efficacy per iRECIST is an exploratory endpoint. AFM24 is administered intravenously once weekly in a 28-day cycle. Tumor assessments are performed at initial screening, cycles 2, 4, 6, 8, and every 3 cycles thereafter. Results: As of December 2022, 14 patients (median [range] age 55 [37–82]; 12 male; 11 Asian, 3 White) were enrolled; the median number of prior therapies was 2.5 (1–12). Median treatment duration with AFM24 was 6.7 weeks (1.0–26.1). Best objective response in 10 evaluable patients was confirmed partial response in 1 patient (change from baseline –45%); 4 patients exhibited stable disease, 1 was confirmed. Tumor shrinkage occurred in 2 patients with stable disease (–6%, –18%). The tumor control rate was 50%. Treatment-related adverse events (TRAEs) were reported in 13 patients; infusion related reactions (IRRs, 12), dermatitis acneiform, neutrophil count decreased, decreased appetite, and myalgia (2 each) were most common. Grade ≥3 TRAEs occurred in 4 patients and included decreased neutrophil count (2), lymphopenia, and IRR (1 each). Grade 5 pneumonitis was observed in 1 patient with disease progression and multiple comorbidities; relation to AFM24 could not be ruled out. As of January 2023, enrollment is ongoing; results of the interim analysis will be presented. Conclusions: AFM24 demonstrated clinical activity and acceptable safety in heavily pretreated patients with EGFR mutant NSCLC. The novel mechanism of action of AFM24 could add to the therapeutic options for patients with EGFR expressing tumors and is under clinical evaluation as a single agent and in combination with atezolizumab or autologous NK cells. Clinical trial information: NCT04259450 .

Supplementary Table S1. Demographic characteristics; Supplementary Table S2. Post-transfusion kinetics of donor NK cells in recipient peripheral blood

Abstract Background: In non-small-cell lung cancer (NSCLC), approximately 3-4% of patients exhibit MET exon 14 skipping (METex14) mutations. ABN401, a selective type I MET kinase inhibitor, has demonstrated promising antitumor activity and safety in advanced solid tumor patients. Here, we report updated outcomes of ABN401, focusing on METex14 NSCLC patients. Methods: Patients enrolled in the ABN401 Phase I (NCT04052971) and Phase II (NCT05541822) trials were analyzed. The safety population consists of all patients who have been dosed at ABN401 800 mg QD, while the efficacy population comprises METex14 NSCLC patients dosed at 800 mg QD. The primary objective for phase I study was safety, and for phase II study was the objective response rate (ORR) in patients. Secondary objectives include recommended dose and regimen of ABN401, PK and preliminary efficacy of ABN401 for phase I and duration of response (DOR), objective disease control rate (DCR), progression free survival (PFS), overall survival (OS), PK, safety, and tolerability of ABN401 for phase II. Results: Between June 23, 2022, and July 6, 2023, a total of 24 patients received ABN401 800 mg QD, including 17 METex14 NSCLC patients. Of 24 patients evaluable for safety, 2 (8.3%) experienced grades ≥3 treatment-related adverse events (TRAE). The most common treatment-related adverse events were nausea (70.8%), vomiting (29.2%), and diarrhea (33.3%). Grade ≥3 treatment-emergent adverse events occurred in 5/24 (20.8%) patients. Treatment-related adverse events leading to permanent discontinuation occurred in 0% (0/24) of patients. Peripheral edema was observed in 29.2% (grade 1-2) and there was no grade 3 or greater event in all safety evaluable populations, and 17.6% (grade 1-2) and 0% (grade 3) in METex14 NSCLC population. For the 17 METex14 NSCLC patients, one was not evaluable because the patient did not had the first tumor assessment at the time of DCO. The median age is 69 (41-81) and 70.6% were male, with 1 (0-3) as the median prior lines of treatment. 41.2% of 17 patients were ex-smoker and 58.8% were non-smoker. All patients were MET inhibitor naïve. The objective response rate was 56.2% (9/16) in the evaluable population. Overall (n = 9), 66.7% is treatment-naïve patients (n = 6). The median duration of treatment was 5.4 months for all who dosed 800 mg QD as of the data cut-off on July 6, 2023. At the time of DCO, data is not mature enough for PFS and DoR. Conclusions: ABN401 has shown promise in antitumor efficacy and favorable toxicity in patients with locally advanced or metastatic METex14 NSCLC. The phase 2 multicenter, open-label trial (NCT05541822) is actively enrolling in the US, South Korea, and Taiwan. Citation Format: Se-Hoon Lee, Ji-Youn Han, Ki Hyeong Lee, Gyeong-Won Lee, Charlotte Lemech, Michael Millward, Aflah Roohullah, Xiuning Le, Keunchil Park, Jun Young Choi, Na Young Kim, Sunyhe Im, Nirmal Rajasekaran, Kyung Eui Park, Sangsuk Lee, Hanlim Moon, Sunjin Hwang, YoungKee Shin, Dae Ho Lee. Efficacy and safety outcomes of ABN401 in NSCLC patients with MET Exon 14 Skipping: A clinically relevant subgroup analysis [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr B042.

Treatment information of patients who received crizotinib

We are focusing on the germline mutation data to understand the possible cancer-causing gene mutation that has a chance of inheritability to the next generation. Cancer genomics has been already widely studied around the world in a pan-cancer manner. But we found that the majority of the ethnicity of the data sequenced is mainly the US and European origin. For the Korean cancer cohort, it is clear that the lack of sample size was the bottleneck for ethnicity-specific studies. It is necessary that there is a limited number of the study contribute to the knowledge that Korean specifically applicated to explore the possible association between germline mutation and cancer occurrences. The objective of this study is to discover the Korean-specific candidate genes that associate with the tumor.Our study collected around 3000 Korean-specific samples consisting of various cancer types and normal control. We also gathered normal control samples for 354 Super-Normal (tumor-free, age < 65, med-checked) samples, and 1094 Korean normal (U1K) samples. Whole Exome Sequencing has been applied for every sample except U1K cohort that has already been whole genome sequenced. Genome-Wide Association Test (GWAS) has been executed between Korean-specific cancer patients and Korean normal samples. The study has been dichotomously analyzed, common variants are studied by GWAS fashion, and the rare variants are studied by gene-level aggregated fashion. Not only statistically, but also functionally we make use of the knowledge that Nonsense Mediated Decay (NMD) information to break the limitation of the unexplained gene mutation that does not follow the Central Dogma. Clinical validation data is also utilized. In a clinical aspect, we validated the dataset with a Clinvar and decided whether the mutation has a piece of clinical evidence or not.By conducting a series of studies, we have successfully found that some candidate genes which are known for DNA binding genes including PABPC1, PABPC3, and ZNF717 were significantly associated. Indeed, a cell division cycle associated gene like CDC27 also represents a significant association with cancer phenotype. Furthermore, ATXN3, SEPT2, PCMTD1 mutation is observed more in the cancer cohort. We are performing comparison studies to further elucidate which ethnic group represents more gene mutation on different cancer types.In summary, we propose the method that presents the possible germline mutation that is associated with phenotype by various factors, and also proposed Korean-specific candidate genes that associate with cancer. Citation Format: Gangpyo Yuh, Seulki Song, Eunju Cho, Miso Kim, Hyery Kim, Youngil Koh, Jookyung Park, Sungsoo Yoon, Sehoon Lee. Unveiling Korean cancer-associated gene using large-size cancer germline mutation data [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 752.

Background: The current standard treatment for limited-stage small-cell lung cancer (LS-SCLC) is chemotherapy with concurrent chemoradiotherapy (CCRT).Methods: In this single-arm phase II study, patients with LS-SCLC received four cycles of etoposide, cisplatin, and durvalumab every 3 weeks. Thoracic radiotherapy of 52.5 Gy in 25 oncedaily fractions was started with the third cycle of chemoimmunotherapy. After CCRT plus durvalumab, patients received durvalumab consolidation therapy every 4 weeks for a maximum of 2 years after study enrolment. Prophylactic cranial irradiation (PCI) was recommended. Results: Fifty-one patients were enrolled, and 50 were included in the full analysis set. With the median follow-up duration of 26.6 months, the median PFS was 14.4 months (95% confidence interval: 10.3-NA), and the 24-month PFS rate was 42.0%. The median overall survival was not reached with a 24-month overall survival rate of 67.8%. The positive PD-L1 group (n Z 22) was not associated with longer PFS (hazard ratio, 0.70; 0.31-1.58) and overall survival (0.64; 0.22-1.84) compared with the negative PD-L1 group (n = 20). Among the 43 patients who were candidates for PCI treatment, the PCI group (n = 22) had significantly fewer events of brain metastasis as the first failure sites compared to the no PCI group (n = 21) (13.6% vs. 42.9%, P = 0.033). There were several grade 3 or 4 adverse events which were well managed with appropriate supportive care.Conclusions: Durvalumab with CCRT for LS-SCLC exhibited promising clinical efficacy with a tolerable safety profile, prompting its validation in a randomized study. Trial registration: NCT03585998. 2022 Elsevier Ltd. All rights reserved.

Background Oropharyngeal squamous cell carcinoma (OPSCC) is the most common neoplasm originating at the base of the tongue or in the tonsils or soft palate. In this study, we investigated the prognostic value of FOXP3+ regulatory T cells in OPSCC. Methods Tumor tissues of patients with locally advanced OPSCC were analyzed using quantitative multiplex immunohistochemistry. Staining of CD8+ T cells, conventional CD4+FOXP3- T cells (Tconv cells), CD4+FOXP3+ regulatory T cells (Treg cells), CD20+ B cells, and CD68+ macrophages was performed, and cell density was evaluated in both the tumor and its stroma. Results Among the 71 patients included in this study, males constituted 93.0% of the cohort, and the median age was 59 years (range: 42-80 years). A total of 56 patients (78.9%) had a smoking history, and 53 (74.6%) patients were positive for human papillomavirus (HPV). The most frequent site of OPSCC was the tonsils (70.4%), followed by the base of the tongue (25.4%). The proportion of Treg cells was lower in the tumors of patients with HPV than in those of patients without HPV. Patients with OPSCC whose tumor Treg cell levels were above the median had longer relapse-free survival (RFS) periods than those with tumor Treg cell levels below the median (HR, 0.12; 95% CI, 0.03-0.46; p = 0.02). Our multivariate analysis identified high Treg levels (HR, 0.13; 95% CI, 0.02-1.00; p = 0.05) as an RFS factor that predicted a good prognosis. Conclusions Our results demonstrated that high Treg cell density in locally advanced OPSCC tumors was correlated with longer RFS.