Background: METex14 mutations was reported in 3~4% of NSCLC patients and became a new target in the treatment of NSCLC. SCC244 is a highly selective and potent oral MET inhibitor. This is the first report of data from an ongoing single-arm phase II study of SCC244 in NSCLC patients with METex14 mutations (GLORY study). Methods: GLORY study is an open label, international, multi-center, single-arm phase II study to evaluate the efficacy and safety of SCC244 in patients with locally advanced or metastatic NSCLC harboring METex14 mutations which was confirmed by central laboratory. The enrolled patients have either failed one or two prior lines of systemic therapies or been not eligible/refused chemotherapy after being well-informed. SCC244 was taken orally at a dose of 300 mg once daily in 21-day treatment cycles until disease progression or intolerable toxicity. Tumor was evaluated every 6 weeks for the first 8 treatment cycles and every 9 weeks thereafter. The primary endpoint was objective response rate (ORR) assessed by blinded independent review committee (BIRC) per RECIST 1.1, secondary endpoints include ORR by investigator assessment (INV), duration of response (DoR), time to response (TTR) and safety etc. Post-hoc analysis was done to explore the intracranial anti-tumor activity. Results: At data cut-off on May 6th, 2021, a total 73 patients screened from 163 patients in 42 sites were treated at 300 mg QD dose and had ≥2 post-baseline tumor assessments or discontinued for any reason. 69 of them were with METex14 mutation confirmed by central laboratory. In the 69 patients, ORR by BIRC was 60.9% (95% CI: 48.4%, 72.4%) overall, 66.7% (95% CI: 50.5, 80.4) and 51.9% (95% CI: 31.9, 71.3) in treatment naïve and previously treated patients respectively. Median DoR was 8.2 months (95% CI: 4.8, NE) and median PFS was 7.6 months (95% CI: 4.2, NE), tumor response from 30 of 42 responders was still ongoing. The response occurred fast with a median TTR of 1.4 months (range: 1.2, 4.2). Partial response was observed in 8 of 10 patients with brain metastasis. 5 patients who had brain metastasis selected as targeted lesion had intracranial response by INV with a median intracranial tumor shrinkage of 57% (range: 34%, 71%). The most common (≥20%) treatment-related adverse events (TRAEs) of any grade were peripheral edema, headache, nausea, loss of appetite, hypoalbuminemia, ALT increase and vomiting. The incidence of ≥ grade 3 TRAEs was 43.8%. TRAEs leading to treatment discontinuation occurred in 6.8% patients, among which peripheral edema was the most common (4.1%). Conclusions: The data shows high and robust efficacy of SCC244 in NSCLC patients with METex14 mutations across treatment lines and encouraging intracranial anti-tumor activity. The safety profile was favorable with manageable toxicity. The data supports SCC244 as a valuable targeted treatment option for METex14 NSCLC patients. Citation Format: Shun Lu, Yongfeng Yu, Jianya Zhou, Koichi Goto, Xingya Li, Jun Sakakibara-Konishi, Kazumi Nishino, Tanaka Kentaro, Lin Wu, Xuhong Min, Wei Zhang, Dingzhi Huang, Yongqian Shu, Chengzhi Zhou, Min Li, Xiaorong Dong, Chong Bai, Lu Li, Jiuwei Cui, Li Zhang, Lejie Cao, Xiaoling Li, AiMin Zang, Haruki Kobayashi, Yiping Zhang, Yan Yu, Xiuwen Wang, Terufumi Kato, Shoichiro Yamamoto, Yuki Shinno, Xiaoyan Lin, Yanqiu Zhao, Yanping Hu, Qitao Yu, Ziping Wang, Masahiro Kodani, Jian Fang, Jialei Wang, Meiqi Shi, Diansheng Zhong, Wen Dong, Hiroshi Tanaka, Yasuto Yoneshima, Minghui Sun, Jun Zhou, Qiuxia Wu, Meng Li. Phase II study of SCC244 in NSCLC patients harboring MET exon 14 skipping (METex14) mutations (GLORY study) [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 CT034.

9101 Background: Furmonertinib (AST2818) is a third-generation epidermal growth factor receptor ( EGFR) tyrosine kinase inhibitor (TKI) with central nervous system (CNS) penetration. Here we report the CNS response to furmonertinib versus gefitinib as first-line therapy in EGFR-mutated non-small cell lung cancer (NSCLC) patients in the FURLONG study. Methods: FURLONG was a randomized, double-blind, multi-center phase III study. Patients were randomized 1:1 to receive first-line furmonertinib 80mg/d or gefitinib 250mg/d. Brain scan was mandatory at screening. Patients with asymptomatic CNS metastases who did not require steroid treatment for 28 days or more were enrolled. A pre-planned CNS efficacy analysis was done using RECIST v1.1 in patients with measurable or non-measurable CNS lesions (cFAS) and patients with only measurable CNS lesions (cEFR). Results: Of 358 enrolled patients in the FURLONG study, 133 (37%) patients were defined as cFAS and 60 (17%) were defined as cEFR according to baseline brain scan judged by a blinded independent review committee (IRC). At the cut-off date of Sep 15, 2021, CNS progression-free survival (PFS) assessed by IRC in the cFAS population was significantly longer in the furmonertinib group than in the gefitinib group (20.8 vs 9.8 months, HR 0.40 [95% 0.23-0.71]; p = 0.0011). CNS PFS rate at 6, 12, 18 months were 91%, 77%, 63% in the furmonertinib group, and 76%, 46%, 34% in the gefitinib group. In the cEFR set, confirmed CNS objective response rate was 91% in patients with furmonertinib and 65% in patients with gefitinib (p = 0.0277), and CNS disease control rate were 100% vs 84% (p = 0.9420), respectively. The mean best percentage change in the sum of target CNS lesion size from baseline in cEFR was -61.8% in the furmonertinib group versus -38.7% in the gefitinib group (p = 0.0011). Conclusions: Furmonertinib showed CNS efficacy as first-line therapy in EGFR-mutated NSCLC patients with CNS lesions. Patients treated with furmonertinib had a reduced risk of CNS progression or death, a higher CNS ORR and a deeper CNS response compared with gefitinib. Clinical trial information: NCT03787992.

9027 Background: GEMSTONE-302, a randomized, double-blind, phase 3 study, previously met its primary endpoint and demonstrated statistically significant and clinically meaningful prolongation of progression-free survival (PFS) with suge+chemo vs placebo+chemo as a 1L treatment in pts with metastatic NSCLC. PFS benefit was observed in both squamous (sq) and non-squamous (nsq) NSCLC, regardless of PD-L1 expression levels. Here we report the data from a protocol pre-specified interim OS analysis. Methods: Pts with systemic treatment-naïve stage IV NSCLC, measurable disease per RECIST v1.1, ECOG PS 0-1, and no known EGFR, ALK, ROS1 and RET alterations were randomized 2:1 to receive suge (1200 mg, IV) or placebo plus chemo (sq-NSCLC: carboplatin+paclitaxel; nsq-NSCLC: carboplatin+pemetrexed) every 3 weeks for up to 4 cycles, followed by maintenance therapy (sq-NSCLC: suge/placebo; nsq-NSCLC: suge/placebo+pemetrexed) for up to 35 cycles. The primary endpoint was investigator assessed PFS (INV-PFS). Key secondary endpoints included OS, INV-PFS in pts with tumor PD-L1 expression ≥1%, and ORR. Pts in the placebo group could cross over to receive suge monotherapy upon disease progression. Results: As of 22 Nov 2021, among all 479 enrolled pts, 51 (15.9%) and 7 (4.4%), respectively, remained on treatment with suge+chemo or placebo+chemo. The median follow-up was 25.4 and 24.9 months, respectively. Following treatment discontinuation, 17.8% and 43.4% of the pts, respectively, received cross-over suge or other non-study anti-PD-(L)1-containing therapies. Median OS was 25.4 months in suge+chemo group vs 16.9 months in placebo+chemo group (HR = 0.65 [95%CI, 0.50-0.84], p = 0.0008), and 2-year OS rate was 51.7% vs 35.6%. OS benefits were observed across all subgroups including different tumor histologies (sq: HR = 0.56; nsq: HR = 0.72) and PD-L1 expression levels (≥1%: HR = 0.64; < 1%: HR = 0.66). In the intent-to-treat population, median PFS was 9.0 months with suge+chemo vs 4.9 months with placebo+chemo (HR = 0.49 [0.40-0.61]), and 2-year PFS rate was 20.8% vs 7.3%. In pts with PD-L1≥1%, the median PFS was 10.9 vs 4.9 months (HR = 0.48 [0.36-0.63], p < 0.0001). ORR was 63.4% vs 40.3% (p < 0.0001). Among pts with baseline brain metastases, suge+chemo improved their OS (HR = 0.45) and intracranial INV-PFS (post-hoc analysis, HR = 0.33) vs placebo+chemo. Safety profile was consistent with previously reported results. Conclusions: Suge plus chemo demonstrated statistically significant and clinically meaningful OS improvement compared with placebo plus chemo, irrespective of tumor histology or PD-L1 expression levels, in pts with newly diagnosed metastatic NSCLC, offering a new 1L treatment option for this group of pts. Clinical trial information: NCT03789604.

Introduction: Extensive-stage small cell lung cancer (ES-SCLC) is associated with limited treatment options and poor prognosis. Immunotherapy has recently showed robust clinical activity in ES-SCLC. In this double-blind, phase 3 trial, we evaluated adebrelimab (SHR-1316), a novel anti-PD-L1 antibody, in combination with standard chemotherapy (chemo) as first-line treatment for ES-SCLC. Methods: Patients naïve to systemic treatment for ES-SCLC were randomized 1:1 to receive 4-6 cycles of adebrelimab (20 mg/kg, iv, d1, q3w) or placebo with carboplatin (AUC 5, d1, q3w) plus etoposide (100 mg/m2, d1, d2, d3, q3w), followed by maintenance therapy with adebrelimab or placebo. The primary endpoint was overall survival (OS). Results: 462 patients were randomized and treated (adebrelimab+chemo, n=230; placebo+chemo, n=232). As of Oct 08, 2021, with an median follow-up of 13.5 mo (all patients; 22.5 mo for patients alive), OS was significantly prolonged with adebrelimab+chemo vs placebo+chemo (median, 15.3 mo [95% CI 13.2-17.5] vs 12.8 mo [95% CI 11.3-13.7]; hazard ratio [HR], 0.72 [95% CI 0.58-0.90], 1-sided p=0.0017); OS rate was 62.9% vs 52.0% at 12 mo and 31.3% vs 17.2% at 24 mo. Progression-free survival (PFS) per independent review committee (IRC) was 5.8 mo (95% CI 5.6-6.9) with adebrelimab+chemo vs 5.6 mo (95% CI 5.5-5.7) with placebo+chemo (HR 0.67, 95% CI 0.54-0.83); PFS rate was 49.4% vs 37.3% at 6 mo and 19.7% vs 5.9% at 12 mo. Objective response rate (ORR) and duration of response (DoR) also favored the adebrelimab+chemo group (Table 1). Grade ≥3 treatment-related adverse events occurred in 85.7% vs 84.9% of patients with adebrelimab+chemo vs placebo+chemo, with the most common (frequency ≥5%) being hematological toxicities in both groups. Conclusions: The addition of adebrelimab to chemotherapy significantly improved OS with an acceptable safety profile, supporting this combination as a new first-line treatment option for ES-SCLC. Efficacy outcomes Adebrelimab+Chemo (n=230) Placebo+Chemo (n=232) Median OS (95% CI), mo 15.3 (13.2-17.5) 12.8 (11.3-13.7) HR (95% CI)*, 1-sided log-rank p 0.72 (0.58-0.90); p=0.0017 12-mo OS rate (95% CI), % 62.9 (56.3-68.8) 52.0 (45.4-58.2) 24-mo OS rate (95% CI), % 31.3 (24.9-37.9) 17.2 (12.1-23.0) Median PFS (95% CI), mo 5.8 (5.6-6.9) 5.6 (5.5-5.7) HR (95% CI)*, 1-sided log-rank p 0.67 (0.54-0.83); p &lt;0.0001 6-mo PFS rate (95% CI), % 49.4 (42.4-56.0) 37.3 (30.7-43.9) 12-mo PFS rate (95% CI), % 19.7 (14.5-25.5) 5.9 (3.1-10.1) IRC-assessed ORR (95% CI), % 70.4 (64.1-76.3) 65.9 (59.5-72.0) Median DoR (95% CI), mo 5.6 (4.6-6.7) 4.6 (4.3-5.5) *Stratified Cox proportional-hazards model Citation Format: Ying Cheng, Jie Wang, Caicun Zhou, Wenxiu Yao, Qiming Wang, Xuhong Min, Gongyan Chen, Xingxiang Xu, Xingya Li, Fei Xu, Yong Fang, Runxiang Yang, Guohua Yu, Youling Gong, Jun Zhao, Yun Fan, Quan Liu, Lejie Cao, Yu Yao, Yunpeng Liu, Xiaoling Li, Jingxun Wu, Zhiyong He, Kaihua Lu, Liyan Jiang, Huiqing Yu, Chengping Hu, Wenhua Zhao, Jian Zhao, Gang Wu, Dingzhi Huang, Chengshui Chen, Cuimin Ding, Baihong Zhang, Xiuwen Wang, Hui Luo, Baolan Li, Ben Zhang, Haowen Li, Ke Ma. Adebrelimab or placebo plus carboplatin and etoposide as first-line treatment for extensive-stage SCLC: A phase 3 trial [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 CT038.

BackgroundAcute respiratory distress syndrome (ARDS) is a serious respiratory disease, caused by severe infection, trauma, shock, inhalation of harmful gases and poisons and presented with acute-onset and high mortality. Timely and accurate identification will be helpful to the treatment and prognosis of ARDS cases. Herein, we report a case of ARDS caused by occupational exposure to waterproofing spray. To our knowledge, inhalation of waterproofing spray is an uncommon cause of ARDS, and what makes our case special is that we ruled out concurrent infections with some pathogens by using metagenomic next-generation sequencing (mNGS) as an auxiliary diagnosis, which presents the most comprehensive etiological examination of similar reports.Case PresentationA previously healthy 25 years old delivery man developed hyperpyrexia, chest tightness, cough and expectoration. The symptoms occurred and gradually exacerbated after exposure to a waterproofing spray. The chest computed tomography (CT) finding showed diffuse ground glass and infiltrative shadows in both lungs. The diagnosis of ARDS related to waterproofing spray was established on the basis of comprehensive differential diagnosis and etiological examination. The patient achieved good curative effect after proper systemic glucocorticoid therapy.ConclusionsThe diagnosis and differential diagnosis of acute respiratory failure for outdoor workers, such as delivery drivers or hikers, should be considered whether toxic aerosol exposure exists from daily contacts. The case can educate the public that more attention should be paid to avoid exposure to these chemicals by aerosols/ingestion mode and some preventive strategies should be taken in occupational environment. The treatment effect of glucocorticoids is significant in ARDS patients with general chemical damage caused by inhaling toxic gases and substances.