NSCLC Stage IV

ROS1 rearrangements are rare, accounting for only 1-2% of NSCLC cases, but have been associated with response to ROS1 inhibitors, such as crizotinib and entrectinib. However, many patients develop resistance to the tyrosine-kinase inhibitors (TKIs), creating a need for new treatments. Repotrectinib is a new-generation TKI designed against ROS1 or NTRK rearranged malignancies (Drilon 2018). Early phase clinical data support activity of repotrectinib in patients with NSCLC harboring such gene rearrangements (TRIDENT-1 study), but there are limited evidence in frail populations, such as poor performance status patients and/or elderly patients, who are classically excluded from clinical trials or underrepresented. The present study aims to assess the activity and tolerability of repotrectinib in frail (PS ≥2) and/or elderly patients with ROS1-rearranged advanced NSCLC.

This is a phase 1/phase 2, multicenter, open-label study to evaluate the safety, tolerability, PK, PD, immunogenicity and preliminary efficacy of M701 in patients with treatment of malignant pleural effusions caused by NSCLC.

The purpose of this study is to see whether adding liver stereotactic ablative radiotherapy/L-SABR to standard drug therapy is better than standard drug therapy alone for people with metastatic non-small cell lung cancer/NSCLC.

This is a randomized, two-cohort, open-label, phase 3, clinical trial to compare the efficacy and safety of N-803 plus tislelizumab and docetaxel (cohort A) or prior failed Health Authority-approved antiprogrammed death-1 (PD-1) or anti-programmed death-ligand 1 (PD-L1) CPI and docetaxel (cohort B) versus docetaxel monotherapy (cohorts A and B). For each cohort, enrolled participants will be randomized 2:1 to treatment in the experimental arm or the control arm. For cohort A, the randomization will be stratified by geographical region (North America vs Europe vs Asia vs Other), NSCLC histology (squamous vs nonsquamous), and actionable genomic alteration (AGA) (epidermal growth factor receptor \[EGFR\]/anaplastic lymphoma kinase \[ALK\]/ROS proto-oncogene 1, receptor tyrosine kinase \[ROS1\] vs Other AGA vs No AGA). For cohort B, the randomization will be stratified by geographical region (Americas vs Asia Pacific \[PAC\] vs Other), NSCLC histology (squamous vs nonsquamous), and actionable genomic alteration (AGA) (Yes vs No).

This prospective, multicenter, real-world observational study aims to evaluate the clinical outcomes of first-line atezolizumab monotherapy in patients with stage IV non-small cell lung cancer (NSCLC) with PD-L1 tumor cell expression ≥50% and no targetable mutations. The study aim to determine how atezolizumab performs in routine clinical practice with respect to survival, treatment response, and safety outcomes in this patient population in Türkiye.

Efficacy and Safety of Sacituzumab Tirumotecan Combined with Furmonertinib in Patients with Locally Advanced or Metastatic Non-squamous Non-Small Cell Lung Cancer Who Have Progressed After EGFR-TKI and Platinum-Based Chemotherapy.

The purpose of this study is to see if adding pirfenidone to atezolizumab will increase anti tumor activity and reduce treatment resistance in stage 4 and recurrent non- small cell lung cancer participants.

This study evaluates the efficacy and safety of Firmonertinib 160 mg once daily in patients with EGFR-mutant, advanced NSCLC who achieve stable disease after first-line Firmonertinib 80 mg for 8 weeks.

This study evaluates the safety, tolerability, maximum tolerated dose (MTD), dose-limiting toxicities (DLTs), and recommended phase II dose (RP2D) of Glecirasib in combination with Ivonescimab in patients with previously untreated, KRAS G12C-mutated, locally advanced or metastatic non-small cell lung cancer (NSCLC) with PD-L1 TPS ≥1%. The study includes a Phase I 3+3 dose-escalation stage followed by a Phase II Simon two-stage design to assess preliminary antitumor efficacy.

The purpose of this study is to evaluate the safety of a cancer peptide vaccine to prevent or delay acquired resistance in advanced ALK+ lung cancer patients currently on ALK targeted therapy.

Androgen Deprivation Therapy (ADT) triggers thymic revitalization and increases thymic output, enhancing baseline anti-tumor immunity and responses to immunotherapies. Anti-tumor synergism has been identified by combining ADT with anti-PD-1 immunotherapy for androgen-independent tumors. This study is to investigate the combination of Leuprorelin ADT and Sintilimab (anti-PD-1) therapy in patients with advanced lung cancer.

Evaluate the efficacy and safety of Anlotinib Hydrochloride in combination with Pemetrexed and Carboplatin versus Pemetrexed and Carboplatin for advanced or locally-advanced Osimertinib-resistant non-squamous non-small cell lung cancer.

The aim of this prospective study is to evaluate the effects of an outpatient pulmonary rehabilitation program on the quality of life, performance and tumor growth of metastatic lung cancer patients receiving ongoing immunotherapy. The main questions it aims to answer are: The primary objective of the study is to assess the effects of outpatient pulmonary rehabilitation (OPR) on exercise capacity measured by difference in the 6-minute walking test (6MWT) in patients with advanced stage lung cancer receiving immunotherapy measured by difference in the 6-minute walking test (6MWT). Secondary endpoints in this study include progression free survival (PFS) and the effect of OPR on long term exercise capacity measured by 6MWT (difference in 6MWT after week 15 and 24). Researchers will compare two groups of patients: one group of patients receives 6 weeks of outpatient pulmonary rehabilitation (intervention group), while the other patient group serves as control since this is standard of care to evaluate the effects of outpatient pulmonary rehabilitation.

Lung cancer is the most common primary cancer of the lung and is responsible for the ever increasing number of cancer-related deaths worldwide. Especially in China, the burden of lung cancer has been rising rapidly due to its large and growing population. Histologically, approximately 85% of lung cancers are non-small-cell lung cancer (NSCLC). Molecular targeted therapy has been shown to dramatically improve the quality of life and survival outcomes of NSCLC patients. One of the most important targeted drugs in NSCLC has been the epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), while there exists some other rare targetable mutation in NSCLC. Emerging evidence underlines that, rather than a single point mutation, some rare mutations present with a wide array of mutations, essentially in NSCLC. Different rare mutations with NSCLC have divergent clinical and therapeutic implications with a particular distinction. Therefore, there is an unmet need for more effective therapies for NSCLC with rare mutations. In summary, identification of genetic alterations in NSCLC with rare mutations is increasingly essential to perform molecular diagnostics and individualized treatments. This project aims to create a registry of patients with NSCLC with rare mutations to further the characterization of molecular alterations and develop (novel) treatments based on the detection.

This study will evaluate whether the combination of sacituzumab govitecan (SG) and bevacizumab will result in shrinkage of brain metastases from patients with non-squamous non-small cell lung cancer (NSCLC), with disease progression on chemotherapy and immunotherapy.

Lung cancer is the second most common cancer in Austria with 2.868 men and 2.009 women diagnosed in 2016. Reflecting the high mortality of this disease, 2.415 men and 1.534 women died from lung cancer. Therefore, lung cancer is the most common reason for cancer associated death in men and second most common reason in women. This malignant disease can be divided into two main groups: small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). NSCLC is a paradigm for personalized medicine, with an increasing number of targetable gene alterations. Despite this growing diversity of molecular subtypes, in most patients no targetable mutation can be detected. For these patients check-point inhibitors with or without chemotherapy is the mainstay of the initial tumor therapy. Until recently, little progress has been made in the treatment of SCLC in last decades. Recently, an overall survival benefit by the addition of an immune-checkpoint inhibitor to first-line chemotherapy for advanced SCLC has been reported. Despite the progress in the treatment of NSCLC, the performance of predictive biomarkers is weak. Therefore, the development of more precise prediction models is of great importance for the progress of personalized treatment strategies.

PACE is a prospective multicenter single-arm investigator-initiated phase II trial that examines the value of a treatment escalation strategy by the addition of platinum-based doublet chemotherapy to osimertinib in patients with treatment-naïve NSCLC harboring L858R or del19 EGFR mutation who are suspected to have poor response upon single-agent TKI treatment.

The goal of our project is building a predictive response algorithm for patients with metastatic lung cancer, exploiting an artificial intelligence platform. It will collect patient information from all areas (clinical, laboratory, radiological, pathological) and analyse them, understanding connections and correlations, both at baseline and at pre-specified timepoints. It would lead to the development of a reliable and constantly evolving predictive score, able to continuously re-weight the importance of each variable as new data come in. Since the greatest clinical need is identifying non-responders to immunotherapy and chemo-immunotherapy combination (30% of all treated patients), these two populations are defined as the starting cohorts (Cohort A, immunotherapy alone, Cohort B, chemo-immunotherapy combinations). For each cohort, three main questions are to be answered: Q1) Early progressors (defined as progressive disease or death within three months of treatment or at first radiological restaging) Q2) Toxicity (with a special focus on severe toxicities G≥3) Q3) Long survivors (defined as patients reaching an overall survival of at least 1.5x median overall survival in registrative trials) The early identification of non-responders, high-risk patients (or on the other hand, long survivors) would help their healthcare planning, providing individualised follow-up strategies or prompting their inclusion in alternative treatments (eg clinical trials). For all cohorts, first data entry will be retrospective and second data entry will be prospective (as validation set).

The study is designed as a prospective, single-arm observational, mixed-method study. Patients with stage IV NSCLC or inoperable mesothelioma will be included and will be treated with immunotherapy according to current guidelines and standard of care. Patients may receive either a PD1/L1 inhibitor monotherapy or, if indicated, together with a CTLA4 inhibitor. Immunotherapy may be administered alone or together with chemotherapy as per site standard/physician's choice. Patients will be given access to a mobile app. Patients will receive daily questions via the app to assess immune-related adverse events between clinic visits and their well-being.

The goal of this clinical trial is to learn if Stereotactic Body Radiotherapy (SBRT) can treat the oligo-progressive metastatic non-small cell lung cancer (NSCLC) after first-line chemotherapy. The main questions it aims to answer are: Does SBRT improve progression-free survival in oligo-progressive metastatic non-small cell lung cancer after first-line chemotherapy? Does SBRT improve overall survival and quality of life in oligo-progressive metastatic non-small cell lung cancer after first-line chemotherapy? Researchers will compare SBRT in combination with standard of care (SOC) and SOC only to see if SBRT works to treat oligo-progressive metastatic non-small cell lung cancer after first-line chemotherapy. Participants will: Take SBRT in combination with SOC or SOC only. Visit the clinic for checkups and tests as required by the study. Keep a diary of their symptoms and complete the quality of life assessment questionnaire.

Non-small cell lung cancer (NSCLC), the most prevalent form of lung cancer, has a significant risk of brain metastasis (BM). Historically, the median overall survival for advanced NSCLC patients with BM was under six months with traditional chemotherapy. However, recent advancements with immune checkpoint inhibitors (ICIs) have shown promise, with some studies reporting improved intracranial objective response rates, progression-free survival, and overall survival when combined with chemotherapy. Despite these improvements, challenges remain, such as treatment resistance, recurrence, and the need for better therapeutic strategies. Local interventions like stereotactic radiotherapy (SRT) and whole brain radiation therapy (WBRT) have been crucial for treating BM, with SRT being particularly effective. The combination of immunotherapy and radiotherapy is emerging as a synergistic approach, with studies suggesting it may enhance local control and survival rates while maintaining safety. Guidelines recommend SRT for patients with limited BMs, and clinical data support the safety and efficacy of combining brain radiotherapy with immunotherapy. A meta-analysis and other studies have shown promising results with this combination, including local control rates and overall survival benefits, with manageable toxicities. However, there is still a need for more prospective clinical trials to verify the safety and efficacy of combining cranial radiotherapy with immunotherapy in NSCLC patients with BM, especially those without driver gene mutations. Therefore, we plan to conduct a phase 2 prospective study, focusing on combining brain radiotherapy with PD-1/PD-L1 inhibitors. We will stratify eligible patients based on the status of BMs (active BM vs stable BM) .

Non-small cell lung cancer (NSCLC), the most prevalent form of lung cancer, has a significant risk of brain metastasis (BM). Historically, the median overall survival for advanced NSCLC patients with BM was under six months with traditional chemotherapy. However, recent advancements with immune checkpoint inhibitors (ICIs) have shown promise, with some studies reporting improved intracranial objective response rates, progression-free survival, and overall survival when combined with chemotherapy. Despite these improvements, challenges remain, such as treatment resistance, recurrence, and the need for better therapeutic strategies. Local interventions like stereotactic radiotherapy (SRT) and whole brain radiation therapy (WBRT) have been crucial for treating BM, with SRT being particularly effective. The combination of immunotherapy and radiotherapy is emerging as a synergistic approach, with studies suggesting it may enhance local control and survival rates while maintaining safety. Guidelines recommend SRT for patients with limited BMs, and clinical data support the safety and efficacy of combining brain radiotherapy with immunotherapy. A meta-analysis and other studies have shown promising results with this combination, including local control rates and overall survival benefits, with manageable toxicities. However, there is still a need for more prospective clinical trials to verify the safety and efficacy of combining cranial radiotherapy with immunotherapy in NSCLC patients with BM, especially those without driver gene mutations. Therefore, we plan to conduct a phase 2 prospective study, focusing on combining brain radiotherapy with PD-1/PD-L1 inhibitors. Though most of the current studies excluded patients with active BM, we believe that these patients need more attention. In this trial, we focus on patients with active BM and treat them with PD-1/PD-L1 inhibitor, chemotherapy and SRT/WBRT.

Although many phase III clinical trials evaluate the quality of life as a secondary endpoint, male sexuality remains a neglected topic in oncology research. In light of the long-term efficacy of new-generation anticancer treatments for ANSCLC (i.e. targeted therapies and immunotherapy), there is a paucity of data about any detrimental effect on fertility and sexuality that could complicate the therapy proposal, especially in young patients. The aim of this trial is to assess incidence of endocrine toxicity and sexual dysfuction in male patients receiving active treatment for ANSCLC

The scope of GALILEO project (Genomic ALteratIons and cLonal EvOlution in ALK+ NSCLC) is to explore the feasibility of genomic longitudinal evaluation for ALK+ NSCLC patients in Italian routine practice and provide a detailed overview of resistance mechanisms and clinical outcomes according to current standard treatments.

This study is a multicenter, randomized controlled clinical trial to explore the preliminary efficacy and safety of treatment response adapted hybrid radiotherapy (LDRT and SBRT) in the first-line treatment of immunotherapy combined with chemotherapy for advanced driver-gene negative NSCLC, and to provide new ideas for the comprehensive treatment of advanced NSCLC