Clinical Research Directory

Preliminary Evaluation of a Large Language Model-Based Tool for Complex Surgical Decision Support in Lung Cancer

This study is an exploratory effect-size estimation study, with the following specific objectives: ① to estimate the point estimate and 95% confidence interval of the Win Ratio for the experimental group (GAPS-Agent) versus the control group (large language model) in blinded pairwise preference judgments by thoracic surgery expert adjudicators, to serve as a sample size planning parameter for subsequent multicenter confirmatory clinical trials; ② to preliminarily evaluate the value of GAPS-Agent within clinical workflows.The hypothesis of this study is as follows: compared with a general-purpose large language model without medical enhancement (control group), a structured agentic workflow optimized on the basis of the GAPS evaluation framework (GAPS-Agent, experimental group) can help junior resident physicians generate clinical decision plans for complex lung cancer cases that are more strongly preferred by senior thoracic surgery expert adjudicators.

Impact of Smoking Cessation Duration on Postoperative Complications in Lung Cancer Surgery

This study aims to investigate the relationship between the duration of smoking cessation before surgery and postoperative complications in lung cancer patients undergoing surgery. Lung cancer surgery patients who have recently quit smoking or are long-term nonsmokers will be evaluated to determine if the timing of smoking cessation impacts the risk of complications after surgery. By analyzing these factors, the study seeks to provide guidance on optimal smoking cessation timing to reduce postoperative risks.

Furmonertinib Plus Radiotherapy for EGFR+ NSCLC With Pleural Effusion

This study is designed as a prospective, multi-center investigation to explore the efficacy and safety of furmonertinib combined with upfront thoracic radiotherapy with or without metastatic lesion radiotherapy in subjects with EGFR-mutant NSCLC and malignant pleural effusion (MPE), aiming to provide additional evidence-based medical support for optimizing the management of NSCLC-MPE subjects. In addition, peripheral blood ctDNA next-generation sequencing (NGS) will be performed at two time points-before the first furmonertinib treatment and one month after the completion of thoracic radiotherapy-to identify subpopulations most likely to benefit from this therapeutic approach and to elucidate resistance mechanisms specific to the radiotherapy-plus-furmonertinib combination, ultimately facilitating more personalized care for these subjects.

Ivonescimab Alone And With Carboplatin/Pemetrexed For NSCLC

The goal of this clinical trial is to assess the efficacy of ivonescimab monotherapy in patients with advanced non-small cell lung cancer harboring actionable genomic alterations who have received prior targeted therapies and chemotherapy. This clinical trial also aims to assess the efficacy of ivonescimab plus carboplatin/pemetrexed chemotherapy in patients with advanced non-small cell lung cancer harboring actionable genomic alterations other than epidermal growth factor receptor mutations who have received prior targeted therapies but no chemotherapy. The main questions it aims to answer are: * Will ivonescimab alone or together with carboplatin/pemetrexed chemotherapy shrink tumors in the clinical trial's patients? * Will ivonescimab alone or together with carboplatin/pemetrexed chemotherapy effectively influence if the patients' cancer grows, how long the treatment takes to start working, how long the treatment keeps working after it first starts to help, how long the treatment keeps the cancer from getting worse, and overall survival of patients? * How many patients receiving ivonescimab alone or together with carboplatin/pemetrexed chemotherapy will experience treatment-emergent, treatment-related, immune-related, and especially interesting side effects? Patients receiving ivonescimab alone will receive an intravenous infusion of ivonescimab every 3 weeks for up to 24 months. Patients receiving ivonescimab together with carboplatin/pemetrexed chemotherapy will receive separate intravenous infusions of ivonescimab, pemetrexed, and carboplatin every 3 weeks for 4 cycles (each cycle is 21 days). These patients will continue to receive infusions of ivonescimab and pemetrexed every 3 weeks for up to 24 total months.

Perioperative Cemiplimab for Resectable Non-Small Cell Lung Cancer With High PD-L1

This is a single arm phase II trial enrolling patients with stage II-IIIA non-small cell lung cancer whose disease is deemed amenable for surgical resection and has a PD-L1 level of ≥50%. Patients will receive cemiplimab for 3 cycles followed by surgical resection. The primary endpoint evaluated by the study is the amount of residual tumor in the resected tissue after 3 cycles of cemiplimab. After surgery, all patients will receive additional 10 cycles of cemiplimab and the treating oncologist will decide on the need of administering chemotherapy prior to that.

Study of RMC-5127 in Patients With Advanced KRAS G12V-Mutant Solid Tumors

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary antitumor activity of RMC-5127 as a monotherapy and in combination with either daraxonrasib or cetuximab in adults with KRAS G12V-mutant solid tumors.

SL-28 for Advanced Solid Tumours

Second Life Therapeutics is developing SL-28, an allogeneic, non-genetically modified cell-based therapy for the treatment of advanced solid tumours. The company has recently demonstrated a novel, non-genetic approach to modulate immune cell activity through targeted manipulation of the Universal Receptive System. The purpose of this open label, multi-center clinical trial is to evaluate the anti-tumor activity, safety, and pharmacokinetics, single-agent SL-28 in patients with a diverse array of solid tumors. The study includes an initial Phase 1 dose escalation to determine recommended dose(s) for expansion of SL-28 as a monotherapy and Phase 2 expansion cohorts. The study will enroll patients with advanced solid tumours, including those who failed previous lines of chemo- and immunotherapies.

Olomorasib + Pembrolizumab KRAS G12C Mutant, PD-L1 TPS 1-49% Locally Advanced or Metastatic NSCLC

This clinical trial evaluates the combination of olomorasib and pembrolizumab as a first-line treatment for patients with advanced or metastatic non-small cell lung cancer (NSCLC) that has a Kirsten Rat Sarcoma Virus (KRAS) G12C mutation and a programmed death-ligand (PD-L1) score between 1% and 49%. The main goal of the study is to determine how long patients live without their cancer worsening after starting treatment, also known as progression-free survival (PFS). Additional goals include evaluating how many patients experience tumor shrinkage or disappearance, how long responses to treatment last, overall survival, and the safety and side effects of the treatment combination. Furthermore, how well the treatment works in patients whose cancer has spread to the brain, outcomes in patients with a lower Eastern Cooperative Oncology Group performance status (ECOG), and whether certain tumor or blood-based biomarkers are associated with treatment response or side effects, if enough patient data is available for analysis.

GCC 2545- Improving Post-Radiotherapy Respiratory Function Through Sparing Serial and Parallel Components in the Lung

Decreased respiratory function is a common side effect experienced by non-small cell lung cancer (NSCLC) patients who receive radiation therapy. In current clinical practice when treating cancerous lesions in the lung, it is not standard to explicitly try and avoid excessive radiation dose and therefore radiation injury to smaller airways. However, because of this patients may obtain damage to an airway segment can cause downstream regions in the lung to lose their "supply line" and, therefore, cause patients to lose the ability to exchange oxygen with the blood. The purpose of this clinical trial is to systematically compare post-treatment lung function of those who receive regular clinical radiation therapy (standard of care \[SoC\]) versus those who receive the airway-sparing radiation therapy regimen. The investigators hope to show that, by preserving airways and connected lung regions, participants will be able to retain a larger amount of their lung function, which will have a direct, positive impact on their post-treatment quality of life.

Observational Basket Trial to Collect Tissue to Develop and Train a Live Tumor Diagnostic Platform (ELEPHAS-02)

The primary objective of this study is to develop and train the Elephas live tumor diagnostic platform and determine the ex-vivo accuracy of the Elephas Score using in-vivo RECIST 1.1 as the reference method

GCC 2546- Motion Management

The purpose of this study is to assess a real time motion tracking of lung tumors and important organs next to the tumor while breathing during a participant's radiation treatment. This will be assessed through a four-dimensional magnetic resonance imaging (MRI) scan before starting your radiation treatment and x-ray fluoroscopy images that are taken during radiation

Practical Geriatric Assessment in Older Adults With Non-Small Cell Lung Cancer Undergoing Stereotactic Body Radiation Therapy

National guidelines recommend that older adults with cancer undergo a special health assessment before starting cancer treatment. This type of assessment evaluates physical function, nutrition, social support, psychological well-being, medical conditions (both cancer-related and non-cancer-related), and cognitive function. The results can help doctors make better treatment decisions and determine whether additional support services-such as nutrition counseling, physical therapy, or social work-would be beneficial. Even though these assessments are recommended, they are not typically used because they need to be performed by a specialist and can take over an hour to complete. Given these challenges, a 10-15-minute assessment called the Practical Geriatric Assessment (PGA) was recently developed. The PGA can be completed by any healthcare provider and helps identify older adults who may need extra support alongside their cancer treatment. While the PGA has the potential to make geriatric assessments more accessible, the investigators do not yet know whether patients will find it useful or easy to complete. Additionally, it is unclear whether using the PGA will lead to more referrals for recommended supportive care services. This study aims to address these questions. The investigators will evaluate whether using the PGA impacts the number of patients referred to recommended supportive care services. Investigators will also evaluate how participants feel about completing the PGA, including how easy or difficult it is, and to assess the feasibility of implementing this survey on a larger scale. Finally, the investigators will use facial photographs and audio-visual data from the PGA to develop and evaluate artificial intelligence algorithm(s) to identify vulnerable patients who might benefit from additional supportive care services; namely, FaceAge, a validated deep learning model capable of estimating biological age from still facial images.

Acute Effects of Visual Feedback-Assisted Inspiratory Muscle Training After Lobectomy

This study aims to evaluate the acute effects of inspiratory muscle training performed with and without a mobile application providing visual feedback on exercise motivation, patient adherence, dyspnea perception, usability, and patient satisfaction in lung cancer patients undergoing lobectomy via video-assisted thoracic surgery. Participants will perform conventional inspiratory muscle training without visual feedback in the morning on postoperative day 1 after transfer to the ward. After at least two hours of rest, the same exercise protocol will be repeated with a smart adaptor connected to a mobile application to provide visual feedback. Inspiratory muscle training will be performed using a threshold-loading device at 40% of maximal inspiratory pressure, with three sets of ten breaths. Outcomes will be assessed before and/or after each session as appropriate.

Symbiotic-Lung-10: A Study to Learn About PF-08634404 Alone or in Combination in Early-stage or Locally Advanced NSCLC

This study is being done to learn more about a new medicine called PF-08634404. The study team wants to understand how well it works when given alone or with chemotherapy. The study is for adults with early stage or locally advanced non-small cell lung cancer (NSCLC) that may or may not be removable with surgery. The study is seeking participants who: * Are aged 18 years or older * Have either: * Early-stage or locally advanced (Stage II or IIIA/B) NSCLC and are a candidate for neoadjuvant therapy, followed by surgical removal of the tumor. Neoadjuvant therapy is a treatment given as a first step to shrink the tumor before surgery. * Early-stage or locally advanced (Stage II or IIIA/B) NSCLC and are a candidate for adjuvant therapy and did not achieve a pathological complete response (pCR) from approved treatment that was administered before surgery. Adjuvant therapy is an additional cancer treatment given after the primary treatment to lower the risk that the cancer will come back. pCR is defined as absence of viable tumor in all surgically removed samples. * Locally advanced (Stage III) NSCLC that may not be removable with surgery, was treated with concurrent chemoradiotherapy (cCRT), and is a candidate for additional treatment, otherwise known as consolidation therapy. cCRT is chemotherapy and radiation given simultaneously. * Be in good physical condition and have healthy organs based on medical tests. * Do not have known actionable changes in DNA The study has 3 parts and each participant will be assigned to one part by their doctor based on their disease diagnosis: * Part A will test PF-08634404 given with chemotherapy in the neoadjuvant setting, followed by surgery. * Part B will test PF-08634404 alone in adults who already were treated with neoadjuvant chemo-immunotherapy, underwent surgery, and did not achieve pCR per tumor tissue pathology analysis. Neoadjuvant chemo-immunotherapy refers to the combination of chemotherapy with immunotherapy per local standard-of-care, given before surgical removal of the tumor. * Part C will test PF-08634404 alone in adults with unresectable disease who received cCRT and did not have progressive disease. Progressive disease refers to a condition that grows, spreads, or worsens. All treatments will be done at clinical study sites, where a trained medical team will monitor adults during and after each visit.

A Study of PHN-012 in Patients With Advanced Solid Tumors

This first-in-human study will evaluate safety, tolerability, anti-tumor activity, immunogenicity, pharmacokinetics and pharmacodynamics of PHN-012, a novel antibody-drug conjugate (ADC), in patients with advanced solid tumors.

Development of New Methodologies and Innovative Tools for the diagnoSi and Therapeutic Treatment of uMAni Epithelial Tumors

The main objective of the SISTEMA project is to develop non-invasive diagnostic tests for the detection and quantification in blood of markers of Mesenchymal Epithelial Transition, a mechanism that characterises certain types of cancer such as breast and lung cancer. Cancer is still one of the leading causes of death in Western countries. In 2014, there were an estimated 1,665,540 new cancer cases and 585,720 deaths in the United States alone. The World Health Organisation (WHO) and Eurostat predict 1,323,600 deaths in Europe, a figure slightly down on previous statistics but still underlining the existence and seriousness of the problem. It is no coincidence that cancer is one of the main areas of investment in the European Horizon 2020 programme. In recent years, the hypothesis that the process of carcinogenesis is driven by the activation of a particular panel of genes/proteins that enable cancer cells to acquire malignant characteristics has become increasingly popular. This process goes by the name Epithelial Mesenchymal Transition (EMT) and characterises all human epithelial tumours. This process allows epithelial tumour cells to acquire mesenchymal characteristics giving them stem, invasive, and chemoresistant properties.

Multimodal CT-Based Risk Stratification for Postoperative Local Recurrence in NSCLC: A Multicenter Study

This multicenter retrospective study is designed to develop and validate a CT-based multimodal risk stratification approach for postoperative local recurrence after curative-intent resection of non-small cell lung cancer (NSCLC). The approach integrates clinicopathologic variables, intratumoral and peritumoral radiomics, tumor-based 2.5D deep learning features, whole-lung deep learning features, and operative text features to capture complementary information related to tumor phenotype, pulmonary background, and surgical findings. Predictive performance and clinical utility will be evaluated in internal and external validation cohorts using the concordance index, time-dependent area under the receiver operating characteristic curve, decision curve analysis, and risk reclassification analyses. The objective of this study is to assess whether multimodal CT-based risk stratification may improve postoperative risk assessment and support individualized surveillance and management strategies.

Phase 1B Trial of Intratumoral Cisplatin for Stage IV Lung Cancer

The addition of intravenous (given through a vein) cisplatin to immunotherapy improves treatment outcomes for lung cancer, but unfortunately results in significantly more side effects since the rest of the body is exposed to significant amounts of the drug. Our clinical trial data indicate that injecting cisplatin directly into the tumor using a bronchoscope (a small flexible tube with a camera in it) has very few side effects, and results in significant cell death and potentially improvement in the immune response. The goal of this proposal is to evaluate a computational approach, that incorporates data from a CT scan, to determine the optimal dose and delivery location within a tumor to maximize tumor cell killing and the immune response.

Osimertinib Plus Capivasertib in NSCLC With PIK3CA/AKT1/PTEN Alterations Following Prior 1L Osimertinib

The goal of this clinical trial is to learn if Osimertinib plus Capivasertib works to treat EGFRm advanced non-small cell lung cancer (NSCLC) in participants with PIK3CA/AKT1/PTEN alterations after progression on first-line Osimertinib (monotherapy or plus chemotherapy). The main questions it aims to answer are: Part A: * Number of Dose-limiting toxicities (DLTs) * Adverse events (AEs)/serious adverse events (SAEs) (graded by CTCAE Version 5.0) * Recommended combined dose (RCD) Part B:Confirmed ORR assessed by the Investigator per RECIST 1.1 criteria. Participants will: Part A:Take Capivasertib twice daily from day 1 to 4 of a 7-day cycle, Osimertinib will be given orally QD(once daily) at 80 mg throughout the study treatment period. Part B: Take Osimertinib (80mg QD, continuously) and Capivasertib(RCD,orally BID from day1-day 4 in 7-day cycle , 4 days on /3 days off) till disease progression (PD) or unacceptable toxicity.

Magnetic Resonance Imaging of the Lung: Oncological Applications

Lung neoplasms are characterized by a complex interaction between tumor cells and a variety of resident and infiltrating host elements, secreted factors, and extracellular matrix proteins, collectively referred to as the microenvironment. Nowadays, in the setting of lung cancer, and in particular non-small cell lung cancer (NSCLC), the evaluation of microenvironment characteristics can only be performed by a pathologist and only on histological material. By combining different MRI parameters, it may be possible to create a specific imaging "signature" for the three different immune phenotypes and thus be able to make a distinction based on MRI examination.

Immune Response to Immunotherapy in Lung Cancer: Study of Sputum and Blood Samples

Lung cancer is the leading cause of cancer-related death worldwide, with nearly 2.48 million cases and 1.8 million deaths in 2022. Despite therapeutic progress, late diagnosis and high mortality make it a major public health issue. Immune checkpoint inhibitors (ICI) such as nivolumab, pembrolizumab, and atezolizumab have improved outcomes for some patients, but only a small proportion benefit, and side effects can be severe. Research is focusing on combining ICIs with chemotherapy, radiotherapy, or other immunotherapies, but reliable biomarkers to predict responders are still lacking. The tumor microenvironment, which promotes resistance, is a promising therapeutic target. The RICEPS study (2021-2023) found specific immune cells and cytokines linked to treatment response, and the ongoing RICEPS-2 trial aims to confirm these findings in a larger group to better understand immune dynamics in lung cancer under ICI therapy.

Phase II Neoadjuvant Study of Garsorasib Followed by Ivonescimab Plus Chemotherapy in Resectable Stage IIA-IIIB KRAS G12C-Mutant NSCLC (GIVEN Study)

This study is a multicenter, prospective, open-label clinical trial. It enrolls previously untreated patients with resectable stage IB-IIIB KRAS G12C mutation-positive NSCLC to evaluate the efficacy and safety of glesorasib sequentially combined with ivonescimab and chemotherapy as perioperative treatment for this patient population.

Tunlametinib Combination Therapy in KRAS-Mutated Unresectable Locally Advanced or Metastatic Non-Small Cell Lung Cancer

This study investigated the efficacy and safety of Tunlametinib Combination Therapy in KRAS-Mutated Unresectable Locally Advanced or Metastatic Non-Small Cell Lung Cancer.

Study to Evaluate the Efficacy and Safety of Adjuvant Tislelizumab in High-Risk Stage I NSCLC

A Randomized, Multicenter, Phase 2 Study to Evaluate the Efficacy and Safety of Adjuvant Tislelizumab in High-Risk Stage I NSCLC