Carcinoma, Pancreatic Ductal

This is a 2-part, Phase 2 study to evaluate the safety, tolerability, dosing, pharmacokinetics (PK), and efficacy of relacorilant in combination with nab-paclitaxel and gemcitabine in chemotherapy-naïve patients with metastatic pancreatic adenocarcinoma (PDAC).

The aim of this study is to assess the clinical value of 5 transcriptomic signatures prognostic of chemotherapeutic sensitivity to improve the Objective Response Rate (ORR) of first-line (L1). Chemotherapy regimen (FOLFIRINOX vs Gem-nabP) will be selected based on transcriptomic signatures applied to the pre-therapeutic liver biopsy of newly diagnosed PDAC patients.

The purpose of this study is to learn about the safety and effects of the study medicine alone or when given together with other anti-cancer therapies. This study also aims to find the best dose. This study is seeking participants who have solid tumors (a mass of abnormal cells that forms a lump or growth in the body) that: * are advanced (cancer that doesn't disappear or stay away with treatment) and * have a KRAS gene mutation (a change in the DNA of the KRAS gene that can cause cells to grow in very high numbers). This includes (but limited to) the following cancer types: Non-Small Cell Lung Cancer (NSCLC): It's a type of lung cancer where the cells grow slowly but often spread to other parts of the body. Colorectal Cancer (CRC): This is a disease where cells in the colon (a part of large intestine) or rectum grow out of control. Pancreatic ductal adenocarcinoma (PDAC): This is a cancer that starts in the ducts of the pancreas but can spread quickly to other parts of the body. Pancreas is a long, flat gland that lies in the abdomen behind the stomach. Pancreas creates enzymes that help with digestion. It also makes hormones that can help control your blood sugar levels. All participants in this study will take the study medication (PF-07934040) as pill by mouth twice a day repeating for 21-day or 28-day cycles. Depending on which part of the study participants are enrolled into they will receive the study medication (PF-07934040 alone or in combination with other anti-cancer medications). These anti-cancer medications will be given in the study clinic by intravenous (IV) that is directly injected into the veins at various times (depending on the treatment) during the 21-day or 28-day cycle. Participants can continue to take the study medication (PF-07934040) and the combination anti-cancer therapy until their cancer is no longer responding. The study will look at the experiences of people receiving the study medicines. This will help see if the study medicines are safe and effective. Participants will be involved in this study for up to 4 years. During this time, they will come into the clinic between 1 to 4 times in each 21-day or 28-day cycle. After they have stopped taking the study medication (at about at 2 years) they will be followed for another two years to see how they are doing.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers, with limited therapeutic options and a five-year survival rate below 10 % in advanced stages. Standard treatments, such as multi-agent chemotherapy, provide only marginal survival benefits and are often associated with significant toxicity. Novel approaches are urgently needed. The ResCPa study is a first-in-human, multicenter, phase I/IIa investigator-initiated trial evaluating the safety, feasibility, and preliminary efficacy of autologous CD318-targeted chimeric antigen receptor (CAR) T-cell therapy in patients with metastatic or locally advanced PDAC that has progressed after standard-of-care treatment. CD318 (also known as CDCP1) is highly expressed in primary and metastatic PDAC tissue but rarely found in healthy tissues, making it a promising and potentially safe immunotherapy target. Preclinical studies have shown potent anti-tumor activity of CD318-CAR-T cells in vitro and in PDAC mouse models without target-specific toxicity. Eligible patients will undergo tumor tissue screening for CD318 expression. Those meeting the criteria will proceed to leukapheresis for autologous T-cell collection. The CD318-CAR construct, optimized in preclinical work, will be introduced via a GMP-produced lentiviral vector, and CAR-T cells will be expanded using automated manufacturing (CliniMACS Prodigy). Following lymphodepleting chemotherapy, patients will receive CD318-CAR-T cells in a dose-escalation design to determine the recommended phase II dose, with the option of dual dosing. The primary objectives are to assess safety, tolerability, and feasibility of manufacturing and delivering CD318-CAR-T cells. Secondary objectives include preliminary anti-tumor activity (objective response rate, progression-free survival, overall survival), CAR-T cell expansion and persistence, and immunological correlates of response or resistance. Patients will be followed for at least 12 months post-infusion, with extended safety follow-up per regulatory requirements. In parallel, an extensive translational research program will investigate CAR-T cell phenotypes, tumor microenvironment changes, and mechanisms of treatment resistance using single-cell multi-omics, spatial proteomics and transcriptomics, organoid co-culture models, and microbiome profiling. Insights from these studies aim to guide optimization of next-generation CAR-T therapies for PDAC and other solid tumors. This trial is conducted by a German academic-industrial consortium including the University Hospital Tübingen, Miltenyi Biotec, University Hospital Freiburg, Klinikum rechts der Isar (TUM), Berlin Institute of Health (BIH), and other partners. The study is supported by the German Federal Ministry of Education and Research (BMBF) within the "National Decade Against Cancer" initiative.

This is a prospective, single-center, single-arm, phase II clinical study. The primary purpose of the study was to evaluate the efficacy and safety of radiotherapy with sequential albumin-bound paclitaxel + Gemcitabine chemotherapy + anti-PD-1 monoclonal antibody and Thymalfasin for borderline resectable pancreatic cancer, and to explore clinical indicators related to efficacy, further guiding subsequent individualized precise treatment.

Study objective: The purpose of this study is to establish a prospective follow-up cohort of high-risk groups of pancreatic cancer, screen early pancreatic cancer through EUS and other means according to the existing clinical process, and evaluate each risk factors. And to prospectively collect biological samples to find molecular markers for early diagnosis of pancreatic cancer. Study design: This is a real world, multicenter, prospective, observational cohort study.