Lynch Syndrome

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 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 studying the effects of naproxen and aspirin on the immune system in people with Lynch Syndrome, a condition that increases the risk of colorectal cancer. This Phase IIa clinical trial aims to understand how these drugs affect the number and types of immune cells, especially T cells, in the normal colon tissue. The study also evaluates impacts on gene expression, immune cell distribution, polyp burden, and the safety of these treatments in participants with Lynch Syndrome. Participants are randomly assigned to take either naproxen or aspirin capsules once daily, at about the same time each day, for an average of one year. The trial includes two treatment groups: one receiving naproxen and the other aspirin. Participants undergo two lower gastrointestinal endoscopies with biopsies, spaced 12 months apart, to assess changes in the colon tissue. The study also monitors the microbiome in normal mucosa, stool, and periodontal areas. During the trial, participants will have regular assessments including tissue biopsies, blood tests, and symptom evaluations. Researchers will measure the abundance of immune cells and gene activity in the colon and endometrium. The study tracks safety and side effects throughout. Participants must agree to follow study rules, including avoiding aspirin or similar drugs outside the study and undergoing yearly colonoscopies. The total involvement lasts about one year, with close monitoring by the research team.

Researchers are evaluating a new, low-cost imaging tool that captures pictures of the lower gastrointestinal (GI) tract without the need for sedation. This device is a capsule about the size of a fish oil or multi-vitamin supplement, attached to a string and connected to a motor. The study includes healthy adults and adults diagnosed with Lynch Syndrome, Crohn's Disease, or Inflammatory Bowel Disease, aiming to assess the device's ability to capture quality images of the lower GI tract. The tool, called the Retrograde Tethered Capsule Endomicroscope (R-TCE) device, is inserted into the participant's lower GI tract and moves upward through a slow spiral motion controlled by the motor. The capsule is connected to an imaging system that saves and displays images in real time. The study will enroll 30 participants who will all receive this same intervention. Participants are grouped into healthy adults and adults with specific gastrointestinal conditions. During the study, the device's image quality and tolerability will be assessed, including participants' experiences without sedation. Imaging data will be collected during the procedure and analyzed within one year. Participants will follow bowel preparation instructions before the procedure. The study will monitor for any adverse effects and evaluate how well the capsule is tolerated on the day of the procedure. Total participation time varies with individual schedules.

Researchers are evaluating oral Alintegimod (7HP349) alone and in combination with ipilimumab, followed by nivolumab monotherapy, in patients with locally advanced or metastatic cancers who have received one or more prior therapies. This open-label Phase Ib dose escalation study is followed by a blinded, randomized multi-cohort Phase 2a comparison of combination versus reference regimens, aiming to assess safety, tolerability, and preliminary efficacy. Participants will receive Alintegimod monotherapy in escalating doses for one cycle, then Alintegimod combined with ipilimumab for four cycles, followed by nivolumab monotherapy for eleven cycles. Alintegimod is given orally as softgel capsules, while ipilimumab and nivolumab are administered intravenously. The treatment continues until the end of the study period, lasting 12 months, unless disease progression or toxicity requires early termination. Throughout the study, participants will undergo assessments including adverse event monitoring, pharmacokinetic testing, and tumor response evaluations using RECIST criteria. Researchers will measure treatment-related side effects, drug levels in the blood, progression-free survival, and overall response rates. Safety will be closely monitored over 18 months, with participants expected to attend regular visits for clinical evaluations and laboratory tests during the study duration.

Researchers are evaluating the safety, tolerability, and effects of NDI-219216 in patients with advanced solid tumors, including those with or without microsatellite instability and deficient mismatch repair. This early phase 1/2 study aims to understand how NDI-219216 affects tumor size, its side effects, and its impact on the body. The trial is sponsored by Nimbus Wadjet, Inc. and includes patients whose tumors are advanced and have not responded to standard treatments or for whom no standard options exist. The study involves three parts: Part A focuses on dose escalation where patients receive increasing doses of NDI-219216 daily in 28-day cycles to find the best dose. Part B randomizes patients into up to three dose groups determined from Part A to further evaluate the treatment daily in 28-day cycles. Part C enrolls patients with specific tumor biomarkers (dMMR/MSI-H) using the optimal dose from Part B. Participants take NDI-219216 orally every day throughout these cycles. Participants visit the clinic six times during the first 28-day cycle, twice in the second cycle, and then monthly for checkups and tests while on treatment. After finishing treatment, there is an end-of-treatment visit and a follow-up that can be done by phone. Patients keep a diary to track their tablet intake and any symptoms. Researchers assess safety by monitoring side effects, tumor response using imaging criteria, and measure drug levels in the blood at scheduled times during the first treatment cycle. The study may last up to 17-18 months depending on the part of the trial.

Researchers are evaluating AMXI-5001, an oral drug that blocks PARP and microtubule polymerization, in adults with advanced cancers that have not responded to other treatments. This Phase I/II trial aims first to find the best dose and then to study the drug's safety and effects in more detail. The study includes participants with several types of advanced cancers, including breast, ovarian, prostate, pancreatic, and other malignant tumors. The trial has two parts: Phase I involves dose escalation, where up to 70 participants receive AMXI-5001 orally twice a day with food on a weekly continuous 7-day schedule, with each treatment cycle lasting 28 days. After determining the recommended dose, Phase II will enroll up to 52 participants to further assess safety, drug levels in the blood, and anti-tumor activity using the chosen dose. All participants receive the study drug as monotherapy. Participants will be monitored for safety, drug concentration in plasma, and tumor response using standard imaging and laboratory tests over approximately 24 months. The primary goals include finding the maximum tolerated dose and recommended dose for Phase II, as well as characterizing the safety profile. Participants must consent and meet eligibility criteria related to their cancer status and overall health. The trial will continue until about October 2026.

Researchers are comparing two bowel cleansing agents, Plenvu and Picoprep, used before colonoscopy to check for colon disease, mainly to exclude cancer. This phase 4 trial investigates whether the newer, low-volume Plenvu is at least as effective as the established Picoprep in cleaning the bowel, while also examining patient tolerability and compliance. The study is conducted at a single center in North Jutland with 400 patients referred for colonoscopy. Participants are randomly assigned to receive either Picoprep or Plenvu. Picoprep involves taking two doses dissolved in water before the procedure, with fluid intake totaling approximately 2.3 liters. Plenvu is taken in a two-day regimen with two separate doses dissolved in 500 ml water each, accompanied by additional fluids for a total of 2 liters. Both agents require dietary restrictions before colonoscopy, including avoiding seed-containing foods five days prior and following a fluid diet the day before. During the study, participants complete a questionnaire about side effects and their experience with the bowel preparation before the colonoscopy. The colonoscopist, who does not know which agent was used, assesses bowel cleansing quality using the Harefield Cleansing Scale. Data on efficacy and tolerability are collected and analyzed. Participants are followed for about 30 hours after the last dose. The trial will end once 400 patients have completed participation.

Researchers are evaluating the use of two cycles of PD-1 blockade with Tislelizumab as adjuvant therapy compared to standard of care in patients with high-risk stage-II dMMR/MSI-H colorectal cancer. This phase III open-label trial aims to see if this approach can improve disease-free survival and overall survival, based on evidence that neoadjuvant immunotherapy reduces tumor recurrence and that short-course treatment may balance benefits with fewer side effects. Participants are randomly assigned to one of two groups. The experimental group receives Tislelizumab 200mg intravenously on day 1 and day 22, with or without adjuvant chemotherapy, while the control group receives standard of care, which may include surveillance alone or chemotherapy options like Capecitabine or CapeOx/FOLFOX. Routine follow-up visits occur every 3 months for the first 3 years and every 6 months during years 4 and 5. Throughout the study, participants undergo evaluations to measure disease-free survival over 3 years and overall survival over 5 years, along with monitoring adverse events up to 30 days after treatment ends. The study involves regular clinical assessments, imaging tests, and safety monitoring to track treatment effects. Enrollment is planned for 180 patients and follow-up extends over several years to assess long-term outcomes.

Researchers are evaluating new approaches to cancer genetic counseling to improve patient engagement with genetics teams. This study includes two trials: the EfFORT Trial focuses on cascade genetic testing, where healthcare providers reach out directly to family members at risk to recommend testing, comparing it to the usual method where patients inform their relatives. The STRIVE Trial studies an online portal intervention to help patients with uncertain genetic test results and their primary care providers stay updated on new information about those results. The EfFORT Trial compares a control group where patients share a family letter with relatives against an intervention group where providers contact relatives directly, offering telegenetics counseling and at-home saliva testing. The STRIVE Trial compares standard care with a digital portal called MyGene Portal, which offers ongoing access to educational materials, communication tools, medical history updates, notifications about result reclassification, and reminders for follow-up visits. Both trials include standard post-test genetic counseling and follow-up recommendations. Participants will be involved through genetic counseling sessions, use of the online portal, and study surveys. Assessments include measuring how often genetic testing occurs in relatives and participant-perceived quality of care over 12 months. Researchers monitor engagement with the interventions, update family medical histories, and provide support for uncertain genetic results. The study is randomized and open-label, with participants actively involved in education, counseling, and communication activities throughout the study period.