Small Cell Lung Cancer

We propose a novel RPM mouse model as a suitable system to mimic MMR-defective SCLC and tumors with high TMB. We provide in vivo evidence that Msh2 deficiency enhances ICI sensitivity. These findings could contribute to stratifying SCLC patients to immunotherapy, thereby improving treatment outcomes.

To evaluate the efficacy and safety of toripalimab plus etoposide and platinum-based chemotherapy (EP) vs placebo plus EP as a first-line treatment for patients with ES-SCLC. The treatment exhibited an acceptable safety profile, supporting this combination regimen as a new treatment option for patients with ES-SCLC. ClinicalTrials.gov Identifier: NCT04012606.

Viability analysis following treatment with pevonedistat and SZL-P1-41 in SCLC cell lines and human SCLC-organoid models indicates that RepID expression determines the sensitivity to CRL-targeting anti-cancer drugs. These findings suggest that RepID represents a novel biomarker for NET and SCLC, and insights from RepID research in these cancers could lead to innovative therapeutic strategies.

Tocilizumab demonstrated significant benefits in survival and various clinical parameters, including body weight, albumin, CRP, mGPS and symptom burden in patients with NSCLC and concurrent IL-6-elevated cachexia. Given the existing unmet medical need for effective interventions for cancer cachexia, tocilizumab may be considered as a potential treatment option.

The CL immunosensor was able to accurately detect the concentration of CYFRA21-1 in serum samples, as evidenced by ELISA results. More importantly, it not only distinguished well between healthy persons and lung cancer patients (90.0% sensitivity and 90.0% specificity), but also effectively distinguished between patients with non-small cell lung cancer and small cell lung cancer (80.0% sensitivity and 86.7% specificity).

Furthermore, it suggests that MYCNOS could serve as a predictor to identify patients who may benefit from NOTCH inhibitors. These findings provide valuable insights for future studies aimed at developing therapeutic strategies targeting these identified pathways.

Consistently, inhibition of PKA also reduced the growth of SCLC cells. These findings offer the initial insight into the role played by sympathetic neurons in the development of SCLC and may open a new therapeutic avenue to treat this deadly malignancy.

These results highlighted the causal effects of chemokines on lung cancer and suggested a mediating role of smoking behavior in the association between chemokines and lung cancer.

Despite the improved outcomes associated with immunotherapy in SCLC, the overall clinical benefit remains modest. Further preclinical and clinical studies are essential to identify optimal treatment regimens and enhance therapeutic efficacy.

P1/2, N=316, Recruiting, Simcha IL-18, Inc. | Active, not recruiting --> Recruiting | Trial completion date: Jan 2025 --> Dec 2025 | Trial primary completion date: Sep 2024 --> Jun 2025

The study found that tarlatamab given every 2 weeks shrank SCLC in participants with SCLC who received previous treatments. Participants given the 10 mg tarlatamab dose had fewer side effects than those given the 100 mg tarlatamab dose.Clinical Trial Registration: NCT05740566 (DeLLphi-304) (ClinicalTrials.gov).

In addition, Gomisin A could also reduce the expression level of the central targets and inhibit the PI3K-Akt signaling pathway. In summary, Gomisin A may be a candidate drug for the treatment of NSCLC, and TNF, AKT1, STAT3, and IL6 are potential targets for Gomisin A in NSCLC treatment, and its therapeutic mechanism may be related to the PI3K-Akt signaling pathway.

NGS, with its capacity for comprehensive genomic analysis, excels in detecting diverse genetic alterations, offering superior resolution compared to CMA. This study supports the use of the PGDx elio tissue complete panel as a compelling alternative to CMA, showcasing its accuracy in assessing the HRD phenotype. The observed high concordance rate further enhances its value in the clinical diagnostic setting.

P1/2, N=250, Recruiting, Daiichi Sankyo | Trial primary completion date: Dec 2024 --> Dec 2025

P1/2, N=39, Completed, Salma Sabbour | Active, not recruiting --> Completed

P=N/A, N=730, Not yet recruiting, Nantes University Hospital | Trial completion date: Sep 2034 --> Dec 2034 | Initiation date: Sep 2024 --> Dec 2024 | Trial primary completion date: Sep 2029 --> Dec 2029

P1/2, N=19, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting | N=12 --> 19

P=N/A, N=206, Recruiting, West China Hospital, Sichuan University; West China Hospital, Sichuan University

P=N/A, N=60, Recruiting, Jilin Cancer Hospital; Jilin Cancer Hospital

P=N/A, N=65, Not yet recruiting, Jilin Cancer Hospital; Jilin Cancer Hospital

P=N/A, N=100, Not yet recruiting, Jilin Cancer Hospital; Jilin Cancer Hospital

P=N/A, N=90, Recruiting, Shanghai Pulmonary Hospital; Shanghai Pulmonary Hospital

P4, N=160, Not yet recruiting, Nanjing Tianyinshan Hospital/Jiangsu Cancer Hospital; Jiangsu Cancer Hospital

P4, N=97, Recruiting, The First Affiliated Hospital of USTC (Anhui Provincial Hospital); The First Affiliated Hospital of USTC (Anhui Provincial Hospital)

P3, N=202, Not yet recruiting, West China Hospital of Sichuan University; West China Hospital of Sichuan University

P3, N=394, Not yet recruiting, Jilin Cancer Hospital; Jilin Cancer Hospital

P3, N=404, Recruiting, Jilin Cancer Hospital; Jilin Cancer Hospital

P2, N=29, Not yet recruiting, Renji Hospital affiliated to Shanghai Jiaotong University School of Medicine; Renji Hospital affiliated to Shanghai Jiaotong University School of Medi

P1, N=48, Not yet recruiting, Taizhou People's Hospital; Taizhou People's Hospital

P1, N=92, Not yet recruiting, Jilin Cancer Hospital; Jilin Cancer Hospital

P2, N=222, Completed, ETOP IBCSG Partners Foundation | Active, not recruiting --> Completed

P2, N=152, Not yet recruiting, VA Office of Research and Development

"This study aimed to predict patient outcomes to immune checkpoint inhibitors (ICI) by developing an integrated DNA/RNA ICI biomarker. A de-identified pan-cancer cohort from the Tempus multimodal real-world database was utilized to develop and validate the Immune Profile Score (IPS) algorithm that leverages Tempus xT (DNA sequencing) and xR (RNA sequencing). The researchers found that IPS status can be used to stratify patient cohorts and prognosticate ICI-treatment response....The team analyzed real-world imaging patterns from a cohort of 4,147 advanced cancer patients treated with immune checkpoint inhibitors (ICI) across five solid tumor types....Incorporating these patterns into a microsimulation model, the team demonstrated that using the molecular biomarker in conjunction with CT imaging provided substantial cost savings and reduced inappropriate therapy compared to imaging alone, with the most benefit observed in small cell lung cancer (SCLC) treated with ICI-chemotherapy."

P=N/A, N=518, Completed, Intergroupe Francophone de Cancerologie Thoracique | Trial completion date: Nov 2021 --> Sep 2024

Maintenance AT improved PFS in patients with SLFN11-positive ES-SCLC that did not progress following initial chemo-immunotherapy. Hematologic toxicity, primarily grade 3 anemia, was increased with AT, as expected. Prospective biomarker-selection was demonstrated, paving the way for future evaluation of novel therapies in molecularly defined SCLC populations.

There is considerable controversy over whether it should be managed as small-cell lung cancer (SCLC) or non-small-cell lung cancer (NSCLC). Therefore, in order to solve the problem of confusion in the selection of treatment regimens for CLCNEC, while also considering the therapeutic effects, this article summarizes and analyzes previous studies, fully seeks evidence, and boldly proposes new therapeutic insights: the etoposide-platinum (EP) regimen serves as the basis for adjuvant therapy; In addition, SCLC/NSCLC-CLCNEC can be distinguished based on presence of RB1 and TP53 co-mutation, and targeted therapy or NSCLC type chemotherapy including platinum + gemcitabine or taxanes (NSCLC-GEM/TAX) can be used in combination or sequentially for NSCLC-CLCNEC.

We characterized the differences between serplulimab with approved PD-1/PD-L1 inhibitors (pembrolizumab and nivolumab) in terms of their binding features and functions in vitro and anti-tumor activity in vivo. Mechanistically, the serplulimab combination effectively reduces tumor microenvironment Treg cell populations, augments effector and memory T cell populations, and more potently modulates genes associated with diverse facets of the immune system, surpassing the effects of the pembrolizumab combination. In summary, our data underscore serplulimab as a differentiated PD-1 monoclonal antibody with best-in-class therapeutic potential.

P1, N=140, Active, not recruiting, Eisai Co., Ltd. | Trial completion date: Aug 2025 --> Mar 2026

P1, N=60, Completed, AstraZeneca | Active, not recruiting --> Completed | Trial completion date: Jan 2025 --> Oct 2024 | Trial primary completion date: Jan 2025 --> Oct 2024

P2, N=28, Recruiting, Jonsson Comprehensive Cancer Center | Trial completion date: Oct 2025 --> Oct 2026 | Trial primary completion date: Oct 2024 --> Oct 2025

SXD had a prophylactic effect in the diarrhea induced by irinotecan, especially for UGT1A1 high-risk population, and this effect from SXD appeared to be maintained the completion of chemotherapy schedule. The mechanism of action of SXD was related to the regulation of inflammatory factors. Trial registration Chinese Clinical Trial Register: ChiCTR1800018490. Registered on 20 September 2018. https://www.chictr.org.cn/showproj.html?proj=25250 . The preliminary protocol of this clinical study has been published in the journal "Trials" in the form of protocol before this paper (Deng et al. in Trials 21:370, 2020).

More trials are needed to prospectively validate the therapeutic heterogeneity among clinicopathological characteristics. https://inplasy.com/inplasy-2023-3-0064/ identifier, INPLASY202330064.