Metastatic Non Small Cell Lung Cancer

Global, Phase 3, randomized, multicenter, open-label study evaluating the efficacy and safety of firmonertinib at a dose level of 240 mg QD compared to investigator's choice of osimertinib (80 mg QD) or afatinib (40 mg QD) in participants who have locally advanced or metastatic NSCLC with EGFR PACC mutations, and who have not received any prior therapy for advanced disease. Participants will be randomized in a 1:1 ratio to treatment with firmonertinib or osimertinib or afatinib and will take the assigned dose daily.

This study, known as LUNAR-2, aims to investigate the effectiveness and safety of using TTFields, delivered by the NovoTTF-200T device, concomitantly administered with pembrolizumab and platinum-based chemotherapy for patients with advanced non-small cell lung cancer that has spread to other parts of the body. The primary goals of the study are to assess overall survival and progression-free survival. Secondary objectives include analyzing outcomes based on the specific histology (subtype) of the lung cancer.

This is a study to investigate the safety and efficacy of an investigational OBX-115 regimen in adult participants with advanced solid tumors.

This is a prospective, open-label, multi-cohort, non-randomized, multicenter phase 2 study evaluating LN-145 in patients with metastatic non-small-cell lung cancer

This is a Phase I open-label clinical trial to assess the safety, feasibility, and preliminary efficacy of intrapleural administration of MOv19-BBz CAR T cells in patients with FRa+ cancers. This study will be initiated in patients with metastatic or recurrent non-small cell lung cancer (NSCLC) only. Subjects will receive a single dose of MOv19-BBz CAR T cells via intrapleural infusion following lymphodepleting chemotherapy. Subjects without an existing intra-pleural catheter will have a temporary pleural catheter placed for the study. Subjects may initiate treatment with commercial checkpoint inhibitors per routine care beginning at least 28 days after receiving MOv19-BBz CAR T cells.

The Phase 2 portion of this study evaluates the efficacy and safety of MRTX849 monotherapy and in combination with pembrolizumab in cohorts of patients with advanced NSCLC with KRAS G12C mutation and any PD-L1 TPS and who are candidates for first-line treatment. The Phase 3 portion of the study compares the efficacy of adagrasib in combination with pembrolizumab versus pembrolizumab in patients with unresectable, locally advanced or metastatic squamous or nonsquamous NSCLC with KRAS G12C mutation and PD-L1 TPS \>=50% and who are candidates for first line treatment.

This study is being done to find out if a new medicine called PF-08634404, when given with chemotherapy, works better than the present standard treatment (pembrolizumab with chemotherapy) for adults with a type of lung cancer called non-small cell lung cancer (NSCLC) that is either locally advanced (spread to nearby tissues) or has spread to other parts of the body. To join the study, participants must meet the following conditions: * Be 18 years or older. * Have locally advanced (Stage IIIB/IIIC) or metastatic (Stage IV) squamous or non-squamous NSCLC. * Is not a candidate for complete surgical resection or curative chemoradiotherapy. * Do not have known actionable genomic alterations * Be treatment naïve for advanced or metastatic disease Participants in this study will be assigned to two different parts of the study depending on their type of tumor: participants with squamous NSCLC will be assigned to Part 1, while participants with non-squamous NSCLC will be assigned to Part 2. Each participant will be randomly assigned (like a flip of the coin) to one of two treatment groups in a blinded fashion: * Part 1 - Arm A or Part 2 - Arm C (Experimental Group): Will receive a new study medicine called PF-08634404 along with a kind of chemotherapy specific to the type of tumor. * Part 1 - Arm B or Part 2 - Arm D (Control Group): Will receive an approved medicine called pembrolizumab along with a kind of chemotherapy specific to the type of tumor. Participants will receive their assigned treatment through intravenous (IV) infusions, which means the medicine is given directly into a vein. The treatment will be given in cycles, participants will receive PF-08634404 or Pembrolizumab in combination with chemotherapy followed by maintenance with either PF-08634404 or Pembrolizumab monotherapy (Part 1) or PF-08634404 or Pembrolizumab in combination with a chemotherapeutic drug (Part 2). Participants will continue receiving treatment if it is helping and not experiencing serious side effects. The study will include regular visits for: * Treatment and health checks: while participant continues receiving treatment. * Tests to monitor how cancer responds: every 6 weeks during the first 48 weeks, then every 12 weeks thereafter.

Background: A type of drug called monoclonal antibody immune checkpoint inhibitors are often used in cancer treatment. These drugs help the body s immune system fight cancer by blocking proteins that cause cancer cells to grow. One of these drugs (atezolizumab) is approved to treat certain cancers. Researchers want to find out if lower doses of this drug might provide the same benefit with fewer adverse effects. Objective: To test different doses and timing of atezolizumab for people with cancer. Eligibility: People aged 18 years and older with cancer that has spread locally or to other organs. They must be eligible for treatment with the study drug. Design: Participants will be screened. They will have blood tests and imaging scans. They will provide a sample of tissue from their tumor. Atezolizumab is administered through a tube attached to a needle inserted into a vein in the arm. Participants will take this drug alone or combined with other drugs prescribed for their care. The first 2 treatments will be done per the FDA recommended dose and schedule. Before administering the second dose of the study drug, researchers will check the level of the drug in the participant s blood. Depending on those results, their 3rd dose will be scheduled 2 to 6 weeks later. For the 3rd dose of the study drug, participants will switch to the FDA minimum dosage. Dosages of any other drugs will not change. Researchers will continue to test the levels of the drug in participants blood before each treatment for 16 weeks. After that, these levels will be tested every 3 months. Study treatment may last up to 2 years.

This study will compare the effectiveness of osimertinib alone with the combination of osimertinib and chemotherapy (carboplatin and pemetrexed) in people with metastatic lung cancer that has a change (mutation) in the gene EGFR. Osimertinib alone is the usual treatment for metastatic EGFR-mutant lung cancer. Researchers think adding chemotherapy to osimertinib could possibly add to the anticancer effects of the usual treatment and help stop cancer from growing or spreading.

Evaluate frequency of adverse events that lead to chemotherapy discontinuation in vulnerable older adults with recurrent/metastatic PD-L1 TPS\<50% NSCLC patients who receive reduced dose chemotherapy in combination with immunotherapy.

This study will assess the effect of Dato-DXd in combination with osimertinib or Dato-DXd monotherapy versus platinum-based doublet chemotherapy in terms of progression-free survival (PFS).

A first in human study to evaluate the safety and preliminary antitumor activity of BBO-8520, a KRAS G12C (ON and OFF) inhibitor, as a single agent and in combination with pembrolizumab and BBO-10203 in subjects with locally advanced and unresectable or metastatic non-small cell lung cancer with a KRAS (Kirsten rat sarcoma) G12C mutation.

The purpose of this study is to evaluate the safety, tolerability, and preliminary efficacy of EDB-102 Injection in patients with advanced non-small cell lung cancer (NSCLC) who have liver metastases. The study specifically targets patients harboring the EGFR-L858R mutation who have disease progression after treatment with third-generation EGFR tyrosine kinase inhibitors (TKIs, e.g., osimertinib). EDB-102 is a novel in vivo gene-editing therapy. It consists of CRISPR-Cas9 mRNA and a single-guide RNA (sgRNA) encapsulated in lipid nanoparticles (LNPs). The drug is designed to specifically identify and disrupt the mutant EGFR-L858R gene in tumor cells, thereby inhibiting tumor growth. Due to the liver-targeting properties of the LNP carrier, this therapy is particularly aimed at patients with liver metastases. This is a Phase I, open-label, dose-escalation study. Participants will receive a single intravenous (IV) infusion of EDB-102. The study will follow a "3+3" design to determine the maximum tolerated dose (MTD) and the recommended Phase II dose (RP2D). Participants will be monitored for adverse events, and tumor biopsies will be collected to assess the gene-editing efficiency of the drug.

This clinical trial is comparing morning infusions of the study drug (pembrolizumab) to random infusion scheduling for patients with non-small cell lung cancer. Participants will be randomized to either the Intervention (Morning Group) where Infusion start times are restricted between 0800 AM and 1000 AM or to the Control (Standard of Care) group where scheduling will occur as standard of care scheduling, in which infusions are scheduled without respect to a specific time of day. There are past studies that suggest the timing of treatment may influence immune response and outcomes. This idea is called chronotherapy. Chronotherapy explores the notion that the timing of drug administration in relation to the body's internal clock can optimize treatment effectiveness. The timing of the infusions for the morning group was therefore, chosen based on data from these past studies that looked at circadian variation in immune system function with the intent to focus on similar infusion windows. The aim of this study is to provide confirmation that the intervention is possible to achieve and use these results to design a larger study. Circadian timing of drug administration, if effective, would represent an intervention that could improve survival outcomes at no additional cost or apparent increase in toxicity, which is truly rare in oncology. Participants are asked to participate in the study intervention for 18 weeks (6 cycles of pembrolizumab), after which participants would continue with ad hoc scheduling as per standard of care.

Standard Maintenance Therapy versus Local Consolidative Radiation Therapy and standard maintenance therapy in 1-5 sites of OligoMetastatic Non-small cell lung cancer (NSCLC): A Phase III Randomized Controlled Trial

The purpose of this study to learn whether PET/CT (positron emission tomography/computed tomography) scans using an imaging agent (radiotracer) called zirconium Zr 89 crefmirlimab berdoxam is a safe and effective way to identify CD8+ T cells

Based on the use of the patient's natural defences, immunotherapy mobilizes the immune system to recognize and destroy cancer cells, and it has revolutionized the treatment of lung cancer. However, the effectiveness of immunotherapy varies from patient to patient. At present, we have no weak markers to predict with certainty the efficacy of immunotherapy treatment in a given individual. Current scientific data identifies a number of molecules produced by the cancer cells and their environment which can be detected by various means (blood tests, breath analysis, etc.). The aim of this study is to understand whether the amount of nitric oxide (NO) present in the breath is a more accurate predictor of response to immunotherapy. Participation in this study involves breath testing (to measure FeNO (Fractional exhaled Nitric Oxide)) before receiving the first infusion of immunotherapy, and at the follow-up visit after the 4th course of immunotherapy.

This study aims to determine if it is feasible to collect samples of blood and viable lung cancer tissue in patients with either: * Stage IV mutation-driven NSCLC * Stage II-III NSCLC undergoing neoadjuvant immunotherapy prior to surgery Viable tissue has been defined by the collaborating pathology department as the presence of viable tumour cells, in accordance with recommendations from the International Association or the Study of Lung Cancer. In patients with stage IV NSCLC, obtaining adequate samples of viable tissue for advanced testing can be challenging, as sites of cancer that are accessible by biopsy are often small, and contain few viable cancer cells. If obtained, however, viable blood and tissue specimens can be utilised for genetic and other analyses aimed at identifying cancer markers that may offer prognostic information, or that may potentially lead to development of therapies that target these markers in the future. In patients with stage II-III NSCLC, the use of immunotherapy prior to surgery has been shown to affect the proportion of viable tumour tissue at the time of surgery, although this needs to be further studied. There is a need to better understand the genetic basis of these tumours to improve response rates to immunotherapy prior to surgery. The study will be open for four years in total. The first three years will consist of recruitment and participant follow up, and the fourth year will consist of follow up only. Data analysis will occur in the fifth year when the study is closed.

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.

The aim of this study is to evaluate the effect of a probiotic supplement containing Bifidobacterium animalis lactis BL-04 on the clinical effectiveness of immunotherapy in patients diagnosed with metastatic non-small cell lung cancer who are receiving immunotherapy.