The purpose of this study is to find out whether ZEN003694 is an effective treatment for people with advanced squamous cell lung cancer with a mutation in the NSD3 gene.
ZEN003694 is a type of drug called a BET inhibitor. Researchers think ZEN003694 may help here because the drug works by blocking a group of proteins called bromodomain and extra-terminal (BET) proteins, which may counteract the effect of NSD3 on tumor growth. Blocking these proteins may slow or stop the growth of the cancer.

Start Date01 Nov 2022

Sponsor / Collaborator

Memorial Sloan Kettering Cancer Center

[+1]

JPRN-UMIN000048656

/ CompletedNot ApplicableIIT

Multicenter Retrospective Study to Evaluate Necitumumab plus Cisplatin/Gemcitabine after Immune-check-point inhibitors in Advanced Squamous-Cell Lung Cancer in Japan (NINJA study) - Multicenter Retrospective Study to Evaluate Necitumumab plus Cisplatin/Gemcitabine after Immune-check-point inhibitors in Advanced Squamous-Cell Lung Cancer in Japan (NINJA study)

Start Date12 Aug 2022

Sponsor / Collaborator

Teikyo University

CTR20213369

/ RecruitingPhase 2

一项HLX07（重组抗EGFR人源化单克隆抗体注射液）+ HLX10 (重组抗PD-1人源化单克隆抗体) + 化疗（卡铂-白蛋白紫杉醇）对比HLX10 + 化疗，对比HLX07 + HLX10一线治疗局部晚期/复发或远处转移肺鳞癌（sqNSCLC）患者的随机、开放、多中心、II期临床研究

[Translation] A randomized, open-label, multicenter, phase II clinical study of HLX07 (recombinant anti-EGFR humanized monoclonal antibody injection) + HLX10 (recombinant anti-PD-1 humanized monoclonal antibody) + chemotherapy (carboplatin-nab-paclitaxel) versus HLX10 + chemotherapy, and HLX07 + HLX10 as first-line treatment for patients with locally advanced/recurrent or distantly metastatic squamous cell lung cancer (sqNSCLC)

主要目的：比较HLX07 + HLX10 + 化疗、HLX10 + 化疗、HLX07 + HLX10在一线治疗局部晚期/复发或远处转移肺鳞癌（sqNSCLC）患者中的临床疗效

[Translation]

Primary objective: To compare the clinical efficacy of HLX07 + HLX10 + chemotherapy, HLX10 + chemotherapy, and HLX07 + HLX10 in the first-line treatment of patients with locally advanced/recurrent or distant metastatic squamous cell lung carcinoma (sqNSCLC)

Start Date04 Jan 2022

Sponsor / Collaborator

Shanghai Henlius Biotech, Inc.

100 Clinical Results associated with Recurrent Squamous Cell Lung Carcinoma

100 Translational Medicine associated with Recurrent Squamous Cell Lung Carcinoma

0 Patents (Medical) associated with Recurrent Squamous Cell Lung Carcinoma

104

Literatures (Medical) associated with Recurrent Squamous Cell Lung Carcinoma

01 Sep 2023·Thoracic cancer

Phase II trial of daily S-1 combined with weekly irinotecan in previously treated patients with advanced or recurrent squamous cell lung cancer: North Japan lung cancer group 1101.

Article

Author: Sugawara, Shunichi ; Ishimoto, Osamu ; Miyauchi, Eisaku ; Usui, Kazuhiro ; Harada, Toshiyuki ; Sakakibara, Tomohiro ; Kawashima, Yosuke ; Inoue, Akira

BACKGROUNDThis phase II trial was designed to evaluate the efficacy and safety of S-1 combined with weekly irinotecan as a second- or third-line treatment for patients with advanced or recurrent squamous cell lung cancer.METHODSPatients with a body surface area <1.25, 1.25-1.50, and >1.50 m² received oral S-1 on days 1-14 at 80, 100, and 120 mg/day, respectively, and irinotecan on days 1 and 8 at 70 mg/m² every 3 weeks. The primary endpoint was the overall response rate, and the secondary endpoints were progression-free survival, overall survival, and the incidence and severity of adverse effects.RESULTSBetween September 2011 and December 2014, 30 patients were enrolled in this study. The overall response rate was 6.7% (95% confidence interval [CI]: 0.8%-22.1%), and the disease control rate was 73.3%. The median progression-free survival was 3.0 months (95% CI: 2.5-3.4 months), and the median overall survival was 10.5 months (95% CI: 5.6-13.7 months). Grade 3/4 treatment-related adverse events were reported in ≥10% of the patients, including leukopenia (21%), neutropenia (21%), anemia (17%), anorexia (10%), and hypokalemia (10%).CONCLUSIONSAlthough the treatment-related adverse events were manageable, the combination of weekly irinotecan and S-1 did not have the expected effect.

01 Jan 2023·Translational Oncology

Single-cell RNA sequencing analysis revealed cellular and molecular immune profiles in lung squamous cell carcinoma

Article

Author: Xiong, Juan ; Lu, Zilong ; Yang, Jinfeng ; Li, Donghang ; Lin, Weichen ; Li, Ning ; Luo, Bin ; He, Ruyuan ; Fan, Tao ; Pan, Shize ; Hao, Bo ; Zhang, Ziyao ; Zhang, Lin ; Meng, Heng ; Geng, Qing ; Song, Congkuan

Although breakthroughs have been made in the treatment of non-small cell lung cancer, there are only a few choices for advanced-stage or recurrent lung squamous cell carcinoma (LUSC) patients. In our study, we identified 7 major cell types in thedepicted the immunolandscape of LUSC microenvironment using single-cell RNA sequencing. We found that an immunosuppressive receptor, T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT), was highly expressed by regulatory T cells (Tregs) and exhausted CD8⁺T cells, suggesting that upregulation of TIGIT might promote an immunosuppressive microenvironment and inhibit the cytotoxic ability of CD8⁺T cells. We also identified tumor-associated neutrophil (TAN), characterized by CXCR2, CSF3R and CXCL8, in the tumor region, and TANs upregulated the expression of interleukin 1 receptor antagonist (IL1RN) which suggested that TAN might exert an immunosuppressive role via expressing IL1RN. Furthermore, the number of SPP1+ macrophages(SPP1⁺M) significantly increased in tumor microenvirnment, which was correlated with the poor survival of patients. Additionally, regulatory networks based on SPP1⁺M revealed that the disparities of several ligand-receptor pairs existed between tumor and normal tissues. Among these pairs, SPP1-CD44 showed the most interactions between SPP1⁺M and other cell types. Our results provided deep insight into the immune landscape of LUSC and an essential resource for drug discovery in the future.

01 Dec 2021·BMC Cancer

Decreased sphingomyelin (t34:1) is a candidate predictor for lung squamous cell carcinoma recurrence after radical surgery: a case-control study

Article

Author: Shiiya, Norihiko ; Funai, Kazuhito ; Eto, Fumihiro ; Takanashi, Yusuke ; Sugimura, Haruhiko ; Tao, Hong ; Kahyo, Tomoaki ; Takahashi, Yutaka ; Kitamoto, Takuya ; Kawase, Akikazu ; Setou, Mitsutoshi ; Mizuno, Kiyomichi

AbstractBackgroundTo reduce disease recurrence after radical surgery for lung squamous cell carcinomas (SQCCs), accurate prediction of recurrent high-risk patients is required for efficient patient selection for adjuvant chemotherapy. Because treatment modalities for recurrent lung SQCCs are scarce compared to lung adenocarcinomas (ADCs), accurately selecting lung SQCC patients for adjuvant chemotherapy after radical surgery is highly important. Predicting lung cancer recurrence with high objectivity is difficult with conventional histopathological prognostic factors; therefore, identification of a novel predictor is expected to be highly beneficial. Lipid metabolism alterations in cancers are known to contribute to cancer progression. Previously, we found that increased sphingomyelin (SM)(d35:1) in lung ADCs is a candidate for an objective recurrence predictor. However, no lipid predictors for lung SQCC recurrence have been identified to date. This study aims to identify candidate lipid predictors for lung SQCC recurrence after radical surgery.MethodsRecurrent (n = 5) and non-recurrent (n = 6) cases of lung SQCC patients who underwent radical surgery were assigned to recurrent and non-recurrent groups, respectively. Extracted lipids from frozen tissue samples of primary lung SQCC were analyzed by liquid chromatography-tandem mass spectrometry. Candidate lipid predictors were screened by comparing the relative expression levels between the recurrent and non-recurrent groups. To compare lipidomic characteristics associated with recurrent SQCCs and ADCs, a meta-analysis combining SQCC (n = 11) and ADC (n = 20) cohorts was conducted.ResultsAmong 1745 screened lipid species, five species were decreased (≤ 0.5 fold change; P < 0.05) and one was increased (≥ 2 fold change; P < 0.05) in the recurrent group. Among the six candidates, the top three final candidates (selected by AUC assessment) were all decreased SM(t34:1) species, showing strong performance in recurrence prediction that is equivalent to that of histopathological prognostic factors. Meta-analysis indicated that decreases in a limited number of SM species were observed in the SQCC cohort as a lipidomic characteristic associated with recurrence, in contrast, significant increases in a broad range of lipids (including SM species) were observed in the ADC cohort.ConclusionWe identified decreased SM(t34:1) as a novel candidate predictor for lung SQCC recurrence. Lung SQCCs and ADCs have opposite lipidomic characteristics concerning for recurrence risk.Trial registrationThis retrospective study was registered at the UMIN Clinical Trial Registry (UMIN000039202) on January 21, 2020.

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