PD-L1

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.

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 evaluating the safety and effectiveness of a combination treatment using adebrelimab and XELOX chemotherapy around the time of surgery for patients with surgically removable gastric cancer or adenocarcinoma of the gastroesophageal junction. This Phase II trial aims to improve outcomes for patients with locally advanced stages of this cancer, as current treatments still face challenges like high recurrence rates despite surgery and chemotherapy. The study focuses on how well this combination approach works before and after surgery to reduce cancer recurrence and improve survival. Participants receive neoadjuvant therapy consisting of three cycles of adebrelimab (1200 mg intravenously every 3 weeks) combined with XELOX chemotherapy (oxaliplatin 130 mg/m2 IV on day 1, and capecitabine 1000 mg/m2 orally twice daily from days 1 to 14, every 3 weeks). Surgery is scheduled within 3 to 6 weeks after this treatment. Following surgery, participants receive five cycles of adjuvant therapy with the same doses of adebrelimab and XELOX chemotherapy. Additionally, adebrelimab maintenance therapy continues for up to one year, with a total of no more than eight cycles of the perioperative combination treatment. During the study, participants will undergo assessments including pathological response evaluation after surgery, imaging, and follow-up visits for up to one year to measure outcomes such as pathological complete response, major pathological response, objective response rate, and survival rates. Researchers will monitor safety through adverse events and serious adverse events. The total study duration includes treatment and follow-up periods, with long-term survival tracked up to three years. This comprehensive monitoring aims to assess the treatment's impact on cancer control and patient well-being.

Researchers are evaluating a blood-based test called Episwitch CiRT4 to see if it can predict how patients with stage III or IV cancer will respond to immune checkpoint inhibitor (ICI) treatments, specifically PD-(L)-1 inhibitors. This observational study aims to compare test predictions with actual patient responses across different types of cancer. The study also explores how social factors might relate to treatment responses and outcomes. Patients who are candidates for or currently receiving ICI therapy will undergo the Episwitch CiRT4 test before starting or during treatment. If the test indicates a high likelihood of response, repeat testing will occur every three months. Participants will be followed for six months to collect data on treatment administered, disease progression, survival, and patient-reported outcomes, along with social determinants of health. Throughout the study, researchers will gather clinical information, including physician questionnaires and patient feedback, to assess outcomes such as disease-free survival and time to recurrence. The study will also analyze health economics related to the test's potential to reduce unnecessary ICI treatments. Monitoring will continue for 24 weeks, with comprehensive data collection to evaluate the correlation between test results, social factors, and patient outcomes.

Researchers are investigating the use of ablation combined with lenvatinib and a PD-1 inhibitor for advanced hepatocellular carcinoma (HCC) with oligometastasis. This study explores a subtype of metastatic HCC where there are limited metastases, aiming to evaluate whether removing these metastases can improve survival. The trial is a multicenter, prospective, phase II study focused on the safety and effectiveness of this combined approach. Participants receive a treatment combining ablation of oligometastases using microwave ablation, radiofrequency ablation, or cryoablation, along with systemic therapy using lenvatinib and PD-1 inhibitors. Ablation targets metastases limited to five sites in no more than two organs, each measuring up to 5 cm. Patients must have already received at least 3 months of lenvatinib and PD-1 inhibitor therapy with controlled intrahepatic tumors before ablation. Throughout the study, participants will be monitored for progression-free survival over 24 months as the primary outcome. Additional assessments include overall survival, objective response rate, and adverse events within 12 to 24 months. Researchers will perform regular evaluations to track treatment response and safety, with the total study duration extending to August 2027.

This research aims to evaluate the effectiveness and safety of combining two drugs, Anlotinib and Toripalimab, as a first treatment option for patients with advanced gastric cancer who have an ECOG performance status of 2. This is a Phase II trial designed to assess this new approach in a group of frail patients with this type of cancer. Anlotinib is a new oral drug targeting multiple growth factor receptors, while Toripalimab is an antibody that may help the immune system fight cancer cells. Participants will receive Anlotinib orally at a dose of 12 mg daily for 14 days out of every 21-day cycle, along with Toripalimab given intravenously at 240 mg on day 1 of each 21-day cycle. This treatment combination will be given as the first-line therapy for their advanced gastric cancer. The trial is a single-arm, open-label study conducted at one center. Throughout the study, researchers will monitor changes in tumor size using standard criteria every eight weeks to evaluate response. They will also track progression-free survival, overall survival, disease control rate, depth of tumor response, and any side effects. Safety assessments will occur regularly, with an average four-week monitoring period for adverse events. Participants' involvement will continue until disease progression, unacceptable toxicity, or withdrawal from the study.

Researchers are evaluating biomarkers from the gastrointestinal microbiome (including bacteria and viruses) and exosomal mRNA expression of PD-L1 and IFNb3 to predict how patients with metastatic melanoma respond to immune checkpoint inhibitor treatments. This study focuses on patients receiving first-line immunotherapy for advanced melanoma, aiming to better understand factors influencing treatment response and immune-related side effects. It is led by the Institute of Oncology Ljubljana and follows patients treated with PD-1 and CTLA-4 inhibitors. Participants provide stool samples before treatment begins, then again around 12 and 28 weeks after starting immunotherapy, as well as at any significant events such as disease progression or immune-related adverse effects. Blood samples are collected at the same times for additional molecular and cytologic testing. Tumor tissue samples are obtained before treatment to analyze relevant biomarkers. The study tracks changes over time in these biological markers to correlate with radiological responses assessed by imaging according to irRECIST criteria. During the study, participants undergo regular imaging scans to evaluate tumor response and provide samples for laboratory analysis. Researchers monitor the composition of the microbiome and expression of specific genes in exosomes to see how they relate to treatment outcomes and side effects. The primary outcome is to assess whether these biomarkers can predict response to immune checkpoint inhibitors over a three-year period. The total participation time depends on treatment and follow-up schedules, with ongoing assessments of safety and disease status.

Researchers are evaluating the clinical efficacy of the Tumour Treatment Vaccine (TTV) combined with PD-1/PD-L1 inhibitors in treating relapsed and refractory advanced solid tumors. Previous studies showed that TTV can enhance the anti-tumor effect of immune checkpoint inhibitor therapy, reaching a tumor suppression rate of 75.96% when combined with PD-1 inhibitors. This study aims to assess this combination treatment from a clinical perspective in patients with advanced solid tumors. The treatment involves administering the tumor treatment vaccine (TTV) by deep subcutaneous injection into the arm or near the tumor. PD-1/L1 inhibitors are used according to their approved indications. The initial TTV dose is 1 ml per injection, which may be increased to 2.5-4.0 ml depending on patient response. The timing between injections can be adjusted based on the patient's condition and reaction. This is an interventional study with an experimental group receiving the combined treatment. Participants will be monitored for tumor relief immediately after the last treatment. The study includes evaluations of measurable lesions using standard criteria and assessments of overall health and treatment response. Participants must comply with follow-up visits and provide informed consent. The study runs from May 2024 to December 2027 and includes safety monitoring and tumor response measurements throughout the treatment period.

Researchers are investigating whether combining surufatinib with immunotherapy and chemoradiotherapy can improve survival for patients with limited-stage small cell lung cancer (LS-SCLC). This single-arm Phase II study explores the safety and effectiveness of adding surufatinib to the standard ADRIATIC regimen, which includes toripalimab and chemoradiotherapy, aiming to enhance treatment outcomes for LS-SCLC patients. Participants will receive four cycles of chemotherapy with etoposide combined with either cisplatin or carboplatin, alongside toripalimab and oral surufatinib taken on days 1 to 14 of each cycle. Radiotherapy to the chest begins no later than the third chemotherapy cycle. After completing chemoradiotherapy, patients who show complete response, partial response, or stable disease will continue with consolidation therapy using toripalimab and surufatinib. Prophylactic cranial irradiation is recommended before starting consolidation treatment. During the study, patients will undergo various assessments to monitor their response and safety, including tracking progression-free survival over two years as the primary outcome. Researchers will also evaluate overall survival, treatment-related side effects, and patient-reported outcomes up to one year after treatment. The total study period involves close monitoring and follow-up to assess both effectiveness and safety of the combined treatment approach.

Researchers are evaluating the combination of Envafolimab with chemoradiotherapy for patients diagnosed with locally advanced nasopharyngeal carcinoma. This prospective, single-arm phase II trial aims to assess the three-year progression-free survival of these patients. Envafolimab is a PD-L1 antibody administered by hypodermic injection, studied here alongside curative chemoradiotherapy to better understand its potential impact on this condition. Participants will first receive three cycles of induction chemotherapy combining GP (gemcitabine plus cisplatin) with Envafolimab. Following this, they will undergo concurrent chemoradiotherapy using intensity-modulated radiotherapy (IMRT) delivering a dose of 68-70 Gy over 30-33 fractions, five days a week for six to seven weeks. During radiotherapy, patients receive two cycles of cisplatin and Envafolimab concurrently. Afterwards, they continue receiving Envafolimab every three weeks for maintenance treatment for up to one year or until disease progression or intolerance. During the study, participants will be closely monitored with regular assessments to track disease progression and treatment tolerance. The main outcome measured is the three-year progression-free survival, reflecting the length of time patients remain free from disease progression. The entire course of treatment and follow-up will span up to one year of maintenance therapy, with ongoing safety and response evaluations throughout the trial period.