Small Cell Lung Cancer

In conclusion, Bergapten exerts its anti-NSCLC effects through the PI3K/AKT pathway, promoting cell senescence and inhibiting inflammation. These findings suggest that Bergapten has potential as a therapeutic agent for NSCLC.

Atirizumab, duvalizumab, atezolizumab, and serplulimab can significantly improve the clinical outcomes of SCLC. Finally, we clarified that the emerging trend of low-dose radiotherapy help overcome the inhibitory signals that limit T-cell infiltration in the tumor matrix. In summary, considering the rapid development of this field, these combined therapy strategies may have unlimited potential to further improve the efficacy of radiotherapy combined with immunotherapy for patients.

P1/2, N=105, Recruiting, Suzhou Zelgen Biopharmaceuticals Co.,Ltd | Not yet recruiting --> Recruiting | Initiation date: Jun 2024 --> Sep 2024

P1, N=65, Recruiting, Abdera Therapeutics Inc.

P1/2, N=78, Recruiting, Suzhou Zelgen Biopharmaceuticals Co.,Ltd | Not yet recruiting --> Recruiting

P2, N=40, Recruiting, ImmunityBio, Inc. | Active, not recruiting --> Recruiting | N=147 --> 40

P=N/A, N=168, Completed, Peking University Cancer Hospital & Institute | Recruiting --> Completed

P1, N=66, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2024 --> Dec 2025

Nomogram integrating clinical factors and pretreatment DLCT radiomic features can help evaluate the EGFR mutation status of patients with NSCLC in a noninvasive way.

We further discussed the factors determining the efficacy of ICIs in EGFR-mutated NSCLC patients, the mutation subtypes and microenvironment characteristics of potential responders. More importantly, we provided insights into areas worth further investigation in the future.

We conducted a comprehensive analysis of the tumor properties, radiological features, and genomic characteristics that are significantly associated with CTCs in different lung cancer subtypes. This study helps elucidate the formation mechanism and relevant major regulation molecules of CTCs.

Functional assays revealed that silencing these genes significantly suppressed SCLC cell proliferation. This study identifies CE as a potential therapeutic agent for SCLC, acting through the suppression of cholesterol synthesis, and uncovers novel therapeutic targets for the treatment of this aggressive cancer.

P1, N=12, Not yet recruiting, Sichuan University

P=N/A, N=180, Enrolling by invitation, Zealand University Hospital

P3, N=180, Recruiting, Luye Pharma Group Ltd. | Not yet recruiting --> Recruiting

Interestingly, our study shows that lurbinectedin treatment upregulates MHC-I/II genes and CD8 in SCLC clinical samples. We provide mechanistic insights into the effect of lurbinectedin on STING-mediated multimodal immune activation and demonstrate that lurbinectedin treatment represents a promising therapeutic strategy to potentiate the efficacy of immunotherapy in SCLC.

The patient was referred for palliative chemotherapy due to the tumor's aggressive nature. This case highlights the clinical presentation and diagnostic challenges of PB with endobronchial invasion.

P=N/A, N=200, Recruiting, European Institute of Oncology

P1/2, N=125, Active, not recruiting, Eisai Co., Ltd. | Phase classification: P1b/2 --> P1/2 | Trial completion date: Jan 2024 --> Mar 2026 | Trial primary completion date: Jan 2024 --> Mar 2026

In this feasibility study, EBUS-MFB was successful in performing PD-L1 testing in 80% of patients with NSCLC.

P2, N=120, Not yet recruiting, Tasly Biopharmaceuticals Co., Ltd.

P3, N=184, Completed, Chipscreen Biosciences, Ltd. | Recruiting --> Completed | Trial completion date: Dec 2025 --> Apr 2024 | Trial primary completion date: Dec 2024 --> Apr 2024

The radiopharmaceutical development and the preclinical/clinical results support the initiation of a first clinical trial to evaluate the therapeutic potential of [177Lu]Lu-DOTA-MGS5 in PRRT.

The results of this study show that the combination can synergistically induce apoptosis of NSCLC by regulating ROS production. EGFR downregulation and AKT/ERK signaling pathway inhibition are linked to the synergistic effect.

P2, N=4, Completed, National Cancer Institute (NCI) | Recruiting --> Completed | N=25 --> 4 | Trial completion date: Dec 2026 --> Feb 2024

P2, N=47, Recruiting, Sun Yat-sen University

In vitro and in vivo, exosomes with high levels of miR-20b-5p were linked to the progression of NSCLC. Our data suggest that exosomes with high levels of miR-20b-5p can increase development and metastasis of NSCLC cells by downregulating TGFBR2, which would serve as a predictive and diagnostic marker for NSCLC.

P1, N=87, Recruiting, Arcus Biosciences, Inc. | Trial completion date: Aug 2025 --> Mar 2026 | Trial primary completion date: Aug 2025 --> Mar 2026

P=N/A, N=1220, Recruiting, AstraZeneca | N=700 --> 1220

P1, N=17, Terminated, Washington University School of Medicine | Active, not recruiting --> Terminated; Futility

Notably, the most promising compound 23e showed a favorable oral PK profile and effectively suppressed the tumor growth in an AML xenograft model. Overall, our medicinal chemistry efforts provide compound 23e as a lead compound for developing LSD1 inhibitors for the treatment of AML and other advanced malignancies.

Most interestingly, the triplet treatment exhibited a safer toxicological profile than the doublet (vinorelbine plus carboplatin) currently applied in the clinical practice. Altogether, these preclinical data support the possibility of repurposing pirfenidone in combination with vinorelbine or with vinorelbine plus carboplatin for NSCLC perioperative treatment, improving therapeutic efficacy while reducing toxicity.

Finally, the combined treatment significantly enhanced the antitumor efficacy of immunotherapy based on PD-1 blockade. The research thereby afforded a novel strategic approach to forestall tumor recurrence after MWA therapy, while also providing the foundational proof-of-concept for impending clinical investigations.

P=N/A, N=111, Not yet recruiting, Oncology Center of Biochemical Education And Research

[225Ac]Ac-EBTATE is safe and effective against SCLC and pan-NET and therefore warrants clinical investigation.

Patients who tested positive for IC had a significantly longer PFS than those who tested negative. Thus, PD-L1 expression may be a predictive factor of efficacy of chemoimmunotherapy in extensive-stage small cell lung cancer.

The MFI of CD47 on the cells in the 10058-F4 group (60.07±0.21) was significantly lower than cells in the control group (70.27±1.37, P＜0.001), but the MFIs of PD-L1 (13.50±0.61) and CD155 (829.70±41.19) were significantly higher than those on the cells in the control group (9.23±0.94, P＜0.01; 496.00±4.36, P＜0.001, respectively). c-Myc may promote the expression of MICA/B and CD47 in Y subtype SCLC cells by binding and inhibiting HDAC1, while it may also be involved in inhibiting the expression of PD-L1 and CD155 in SCLC cells.

Her tumor strongly expressed DLL3 protein and had clinical response to tarlatamab therapy. This case indicates that this novel therapy may be an efficacious option in other pulmonary neuroendocrine cancers.

Silencing DAXX or GLUT4, or treatment with 2-Deoxy-d-glucose (2-DG, a glycolysis inhibitor) reversed the effects of CALML3-AS1 overexpression on aerobic glycolysis, malignant growth, and stemness of SCLC cells...Knockdown of CALML3-AS1 or DAXX inhibited tumor growth in SCLC in vivo. In conclusion, CALML3-AS1, an oncogene, promotes the malignancy and stemness of SCLC cells by interacting with DAXX to enhance GLUT4-mediated aerobic glycolysis, thereby promoting SCLC progression.

P3, N=180, Recruiting, Chipscreen Biosciences, Ltd. | Trial completion date: Dec 2024 --> Dec 2025

P3, N=439, Not yet recruiting, BioNTech SE

The therapeutic vulnerabilities associated with POU2F3 expression in SCLC suggest that a similar approach might be considered for POU2F3-positive carcinomas of the sinonasal tract. Given their diagnostic and possible therapeutic relevance, nNEM have potential to transform the way we approach the diagnosis and management of sinonasal small round epithelial/neuroepithelial malignancies.