Immunotherapy

Researchers are evaluating 177Lu-RAD204, a radiolabeled antibody targeting PD-L1, in a Phase 0/1 study involving participants with advanced solid tumors that express PD-L1. The study aims to assess the safety, tolerability, biodistribution, radiation dosimetry, and preliminary anti-tumor effects of this treatment. The main goal is to find the maximum tolerated dose and recommended doses for future studies in participants with cancers such as NSCLC, SCLC, triple-negative breast cancer, melanoma, head and neck cancer, endometrial cancer, and others with specific genetic markers. The study includes a pre-screening period for PD-L1 testing if needed, followed by a screening period lasting up to four weeks. Participants undergo a Phase 0 Imaging Period where a low dose of 177Lu-RAD204 is given to assess imaging quality, safety, and dosimetry over two weeks. This may be followed by a Phase 1 Treatment Period with escalating doses of 177Lu-RAD204 administered in cycles lasting six weeks each. Participants may receive multiple treatment cycles based on clinical benefit and safety evaluations. Dose-limiting toxicity is monitored for six weeks after the first treatment dose, and dosing intervals may be adjusted as agreed by the study team. During the study, participants will have imaging scans, safety evaluations, and laboratory tests to track the distribution and effects of 177Lu-RAD204. Researchers will measure pharmacokinetics, radiation dosimetry, and tumor responses up to 30 weeks. Safety and tolerability are closely monitored throughout. Participants must meet specific health and tumor criteria to join and will be observed for any adverse reactions. The total duration of participation varies depending on treatment response and tolerability.

Researchers are studying the use of 3'-deoxy-3'-[18F] fluorothymidine (FLT) positron emission tomography (PET) imaging in patients with cancer. This phase I trial aims to evaluate how well FLT PET imaging measures tumor growth and the activity of the DNA synthetic pathway in various cancers, including solid tumors and blood cancers. The study also seeks to determine how effective this imaging method is at detecting lesions and assessing response to treatment. Participants receive up to four FLT PET imaging procedures. During each procedure, a small amount of the FLT tracer compound is injected into the vein, followed by PET scan data collection for two hours to measure tumor growth. Blood samples may be taken during the scans, and urine samples collected afterward to analyze breakdown products of the tracer. Throughout the study, patients undergo assessments including PET or CT PET scans to measure tracer uptake and retention in tumors and normal organs. Researchers also evaluate changes in key enzymes related to DNA synthesis before and after therapy. These evaluations help monitor tumor activity and treatment response. The total time participants spend in the scanner during imaging is up to two hours per session, with a focus on capturing detailed tumor growth information.

Researchers are evaluating a new preoperative method using three-dimensional CT scans and virtual resection simulation to predict lung function after surgery in patients with non-small cell lung cancer (NSCLC) undergoing Video-Assisted Thoracoscopic Surgery (VATS). This study aims to improve accuracy over traditional methods by accounting for differences in lung ventilation caused by tumors or emphysema. It is a prospective, multi-center, longitudinal cohort study involving 60 patients split evenly between those having lobectomy and segmentectomy. Participants will undergo detailed thin-slice chest CT scans and pulmonary function tests before surgery. Using Synapse 3-D software, doctors will create patient-specific 3-D lung models to simulate the planned lung tissue removal and calculate the fraction of ventilated lung to be resected. After surgery, patients will follow standard VATS procedures. The study includes long-term follow-up with pulmonary function tests at 3, 6, and 12 months and CT scans at 6 and 12 months to observe structural lung changes. During the study, participants will have preoperative assessments, surgery, and several postoperative visits for lung function tests and imaging. Researchers will measure how closely the predicted lung function matches actual results at 3 months, as well as longer-term accuracy at 6 and 12 months. They will also study how well the remaining lung compensates after surgery and the effect of any complications on recovery. The total participation spans about one year after surgery, allowing detailed evaluation of lung function and recovery.

Researchers are evaluating the safety and effectiveness of different courses of pembrolizumab combined with carboplatin and albumin-binding paclitaxel as preoperative (neoadjuvant) therapy in patients with resectable head and neck squamous cell carcinoma (stages T3 or T4, N0). This phase II, prospective, randomized study aims to compare four treatment cycles versus two cycles and assess outcomes such as pathological complete response, adverse events, survival rates, and radiological responses. The study also explores various factors that could influence treatment response and prognosis. Participants are randomly assigned to receive either four cycles or two cycles of pembrolizumab (200 mg IV), carboplatin (300 mg/m2 IV), and albumin-bound paclitaxel (260 mg/m2 IV) every 21 days, followed by surgery. Each treatment cycle occurs on day 1, and continuation depends on absence of disease progression or unacceptable toxicity. The study collects clinical, pathological, imaging, and serological data before and after treatment to evaluate the therapies. During the study, participants undergo assessments including imaging, pathology examination of tumor tissues, and laboratory tests. Researchers monitor adverse events for 90 days post-surgery and measure pathological response six weeks after treatment initiation. Longer-term outcomes such as event-free and overall survival are tracked for up to five years. Data on operation delays and radiographic responses are also gathered to assess treatment safety and efficacy throughout the study duration.

Researchers are developing advanced four-dimensional magnetic resonance imaging (4D-MRI) techniques to create detailed, moving images of the lungs and liver in adults. This imaging method produces three-dimensional movies that capture organ motion during breathing, which is important for improving radiation therapy planning for lung and liver cancer patients. The study aims to overcome challenges in current imaging methods to better target tumors that move with respiration. The study includes two main parts: technical development of ultra-quality 4D-MRI in healthy volunteers and evaluation of the technique in cancer patients. This involves creating a new MRI pulse sequence and image reconstruction process to achieve high spatial and temporal resolution with minimal motion artifacts. Researchers will compare the new 4D-MRI method to existing imaging and registration techniques in both healthy volunteers and patients with lung or liver tumors undergoing radiation therapy. Participants will undergo a single imaging session lasting up to two hours involving 4D-MRI scans. Healthy volunteers and cancer patients will be assessed to measure image quality and accuracy of motion modeling. The study will monitor how well the 4D-MRI technique captures tumor movement compared to current methods. The total participation time is limited to the imaging session, with no long-term follow-up mentioned.

Researchers are evaluating the use of 68Ga-grazytracer PET imaging to help diagnose pseudoprogression in lung cancer patients after immunotherapy. Pseudoprogression is difficult to distinguish with current clinical methods, which often require follow-up observations that may not meet clinical needs. This study aims to assess the effectiveness and feasibility of this novel imaging agent, which targets granzyme B to show the activity of cytotoxic T cells in tumor areas. This observational study uses 68Ga-grazytracer PET/CT scans to visualize and semi-quantitatively measure granzyme B concentration in lung cancer lesions that have enlarged or developed new lesions after immune checkpoint inhibitor treatment. The study follows patients for 4-8 weeks, up to a maximum of 12 weeks, to evaluate the diagnostic performance of this imaging method in detecting pseudoprogression. Participants will undergo PET/CT imaging and be monitored over the follow-up period to assess changes and outcomes. Researchers will collect data on diagnostic accuracy and safety during this time. The study includes adult lung cancer patients aged 18 to 75 years who meet specific clinical criteria and have a life expectancy of at least six months. Total participation duration varies with the follow-up period, and patient compliance with study requirements is monitored throughout.

This research aims to assess how well 68Ga-NK224 positron emission tomography/computed tomography (PET/CT) can measure PD-L1 expression in primary and metastatic tumors in people with cancer. It compares PET/CT imaging results with tissue analysis through histopathology to better understand tumor characteristics. The study focuses on adults diagnosed with malignant tumors and evaluates imaging technology for its diagnostic value. Each participant receives a single intravenous injection of the imaging agent 68Ga-NK224, followed by PET/CT scans to capture images of tumors. Tumor uptake is measured using maximum and mean standardized uptake values (SUVmax and SUVmean). The PD-L1 expression in the tumors is then confirmed by examining tissue samples. This evaluation helps compare the imaging results with actual tissue findings. Participants undergo the PET/CT imaging and tissue analysis, with data collected to assess the agreement between imaging and histopathological results within 30 days. Researchers also evaluate variability in PD-L1 expression within and between tumors. Participants may be followed for up to 30 days to monitor outcomes. The study involves adults aged 18 to 90 years and includes patients with both newly diagnosed and previously treated cancers.

Researchers are studying the stimulator of interferon gene (STING) protein, which plays an important role in the immune system's ability to detect tumors. This trial focuses on evaluating a new imaging agent called [68Ga]Ga-Sa-DABI-4, designed to noninvasively detect STING expression in the tumor environment using positron emission tomography (PET). The study aims to assess the safety, distribution in the body, and potential usefulness of this imaging agent for cancer patients. Participants will receive one intravenous injection of the investigational drug [68Ga]Ga-Sa-DABI-4 during the study. This single administration is followed by PET imaging to monitor how the agent interacts with the tumor. The study is conducted in an early phase 1 design, focusing on initial safety and diagnostic capabilities. During the trial, participants will undergo PET scans to evaluate the diagnostic effectiveness of the imaging agent within 15 days after injection. Researchers will monitor safety and how the drug distributes throughout the body. The study includes patients suspected of having or newly diagnosed with malignant diseases. Participation involves a single dosing and imaging session, with safety and diagnostic data collected during this period.

Researchers are evaluating MDNA11, a long-acting "beta-only" recombinant interleukin-2 designed to activate immune cells that kill cancer while minimizing activation of immunosuppressive cells. This Phase 1/2 study aims to assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and early anti-tumor activity of MDNA11 alone or combined with the checkpoint inhibitor pembrolizumab in patients with advanced solid tumors. The study is conducted at multiple sites with regulatory and ethical approvals and includes about 115 patients. The trial has several parts: dose escalation and expansion for MDNA11 monotherapy and for its combination with pembrolizumab. MDNA11 is given intravenously every two weeks with doses adjusted to find the recommended dose for expansion. Tumor assessments using CT or MRI scans happen every 8 weeks to monitor response until disease progression or other study-end criteria occur. Treatment may continue beyond progression under certain conditions. Participants undergo evaluations including tumor imaging, laboratory tests, and safety monitoring over up to 24 months. Researchers measure recommended dose levels, treatment-related adverse events, pharmacokinetics, immune response, and anti-tumor activity such as response rates and progression-free survival. Patients can withdraw anytime, and safety follow-up continues to understand MDNA11's effects alone and with pembrolizumab.

Researchers are evaluating the effectiveness of combining JMT101, a recombinant humanized anti-EGFR monoclonal antibody, with osimertinib, an EGFR tyrosine kinase inhibitor, compared to osimertinib alone. This Phase 3, randomized, positive-controlled, open-label study focuses on patients with newly diagnosed locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) that has EGFR-sensitive mutations. The aim is to assess whether the combination improves treatment outcomes for this specific lung cancer type. Participants receive either JMT101 intravenously every two weeks along with daily oral osimertinib, or osimertinib alone taken orally daily. Each treatment cycle lasts four weeks. This study is designed to compare these two treatment approaches as first-line therapy for the specified lung cancer patients. Treatment and monitoring continue for up to approximately 44 months after the first participant is enrolled. During the study, participants undergo regular assessments including imaging scans evaluated by an independent review committee using RECIST 1.1 criteria to measure progression-free survival and other response rates. Researchers also monitor overall survival, adverse events, and immune responses to JMT101. Laboratory tests assess blood counts, organ function, and antibody levels. The study includes ongoing safety monitoring and long-term follow-up visits to evaluate treatment effects and tolerability.