Colorectal Cancer (CRC)

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary antitumor activity of RAS(ON) inhibitors in combination with ivonescimab in adults with advanced or metastatic solid tumors with a RAS mutation.

The purpose of Part 1 of this study is to evaluate the imaging characteristics, safety, biodistribution and pharmacokinetics of \[68Ga\]Ga-DFC413, and in Part 2 compare to \[68Ga\]Ga-NNS309 in patients with locally advanced or metastatic pancreatic ductal adenocarcinoma (PDAC), non-small cell lung cancer (NSCLC), HR+/HER2- ductal and lobular breast cancer (BC), triple negative breast cancer (TNBC), colorectal cancer (CRC), and soft tissue sarcoma (STS). In Part 2 of this study (comparison of \[68Ga\]Ga-DFC413 and \[68Ga\]Ga-NNS309), not all indications might be explored.

The study aims to evaluate the effectiveness of artificial intelligence-assisted colonoscopy in increasing adenoma detection rate and the accuracy in the characterization of colorectal lesions, compared to standard colonoscopy, in a randomized controlled clinical trial setting.

This is a multicenter Phase 1b, open label, dose-escalation and cohort-expansion study, evaluating the safety, tolerability, pharmacokinetics (PK), preliminary antitumor activity, and effect of biomarkers of zanzalintinib administered alone, and in combination with nivolumab (doublet), nivolumab + ipilimumab (triplet) and nivolumab + relatlimab (triplet) in participants with advanced solid tumors. In the Expansion Stage, the safety and efficacy of zanzalintinib as monotherapy and in combination therapy will be further evaluated in tumor-specific Expansion Cohorts.

This study is to evaluate the safety and tolerability to determine (i) the recommended Phase 2 dose (RP2D) of VMD-102 (Phase 1), and (ii) preliminary anti-tumor efficacy (Phase 2), in participants with advanced HCC, metastatic uveal melanoma (MUM), renal cell carcinoma (RCC), non-small cell lung cancer (NSCLC), and colorectal cancer (CRC). The pharmacokinetics (PK), preliminary anti-tumor activity, and potential biomarkers of VMD-102 will also be assessed. VMD-102 will be the first selective PKC epsilon (PKCε or PKCe) kinase inhibitor to enter human clinical testing. Preclinical VMD-102 anti-tumor activities in mouse liver/HCC tumor models and preclinical toxicology and pharmacology studies support this study.

This study aims to evaluate the safety, tolerability, and efficacy of pirfenidone and PD-1 monoclonal antibody combined with or without hypofractionated radiotherapy in the treatment of advanced refractory pMMR/MSS colorectal cancer patients.

This is an open-label multicenter, single-arm Phase II study of Fruquintinib in combination with FOLFIRI (leucovorin calcium (folinic acid), fluorouracil, and irinotecan) in participants with metastatic colorectal cancer (mCRC). The main goals of this study are to: * Evaluate the efficacy of the combination of fruquintinib + FOLFIRI in the 2nd-line mCRC setting * Evaluate the safety of the combination of fruquintinib + FOLFIRI

This study will investigate the safety, tolerability, pharmacokinetics, and anti-tumor activity of CBI-1214 in participants with advanced or metastatic Microsatellite Stable (MSS)/Microsatellite Instability Low (MSI-L) Colorectal Cancer

The purpose of this study is to investigate the study drug, OKN4395, administered alone and in combination with pembrolizumab. The overall objectives of this study are to determine the safety and tolerability (degree to which side effects of a drug can be tolerated) of OKN4395 alone and in combination with pembrolizumab, OKN4395 and metabolites (broken-down substances) of OKN4395 levels in the blood, and antitumor activity of OKN4395 alone and in combination with pembrolizumab. This study will be split into 2 parts. Part 1a will look at multiple doses of OKN4395 either alone (monotherapy) or with pembrolizumab (combination therapy) administered on day 1 of each 21-day cycle in patients with solid tumors until the participant has disease progression or discontinues for any reason. The dose of OKN4395 will be increased, after each group of 3 or more participants completes their first 3 weeks of treatment and their data is evaluated for safety, with a planned dose range from 10 mg twice a day to 450 mg twice a day through 13 dose levels. Part 1a also includes a parallel substudy (Substudy 1) consisting of at least 12 participants, aiming to test the effect of food and stomach acid on the levels of OKN4395 in the blood as well as its tolerability. Part 1b will evaluate OKN4395 alone and in combination with pembrolizumab administered on day 1 of each 21-day cycle in patients with selected cancer types. Part 1b will comprise 4 cohorts: Cohort 1 in sarcoma (OKN4395 alone), Cohort 2 in non-small cell lung cancer (NSCLC), Cohort 3 in colorectal cancer, and Cohort 4 in gastric cancer (GC), with cohorts 2 to 4 in combination with pembrolizumab. The overall study will enrol approximately 146 participants with up to 54 participants to receive OKN4395 alone and 12 participants to receive OKN4395 in combination with pembrolizumab in Part 1a, and 80 participants in Part 1b split: 20 on monotherapy and 60 on combination therapy. The study will be conducted in the US, Australia, UK and in the EU.

Colorectal cancer (CRC) is one of the most common malignant tumors. With the rapid development of China's economy, people's living standards have been significantly improved, and lifestyles and dietary structures have changed. Smoking, drinking, high-fat, high-energy diets, etc. have led to an increase in the incidence of colorectal cancer year by year. Data show that in 2022, there will be 510,000 new cases of colorectal cancer in China, and about 240,000 deaths related to colorectal cancer. Radical surgery is the main initial treatment for early and middle-stage colorectal cancer and some metastatic colorectal cancer. Although the level of surgical treatment of colorectal cancer has been greatly improved and can achieve cure for some patients, its 5-year overall survival rate is only about 60%, and the main cause of death is distant metastasis and recurrence. In recent years, with the in-depth understanding of the treatment mechanism of metastatic colorectal cancer (mCRC), a variety of new treatment options have been proposed and applied in clinical practice in order to improve the quality of life of patients and prolong their survival. Trifluridine/tipivirine (TAS-102) is a new type of cytotoxic drug that exerts anti-tumor effects by directly incorporating into DNA chains to destroy DNA function. Its mechanism of action is different from that of fluorouracil drugs, and it can resist 5-fluorouracil (5-FU) resistance, providing a new treatment option for mCRC patients. TAS-102 has been approved in China for mCRC patients who have previously received fluoropyrimidine, oxaliplatin, and irinotecan-based chemotherapy, as well as those who have previously received or are not suitable for anti-vascular endothelial growth factor (VEGF) therapy and anti-epidermal growth factor receptor (EGFR) therapy (RAS wild type). Bevacizumab, as a monoclonal antibody targeting VEGF, exerts its anti-tumor effect by inhibiting tumor angiogenesis. Putlimumab, as an immune checkpoint inhibitor, enhances the body's immune response to tumors by blocking the PD-1/PD-L1 signaling pathway. Combination therapy has attracted much attention due to its possible synergistic effect. Studies have shown that TAS-102 combined with bevacizumab can achieve longer overall survival (OS) than TAS-102 monotherapy. In addition, TAS-102 combined with bevacizumab for refractory mCRC has also been approved by the FDA, showing its potential and importance in the treatment of mCRC. Therefore, this study aims to explore the efficacy and safety of TAS-102 combined with bevacizumab and putelimab in patients with mCRC after cytoreductive surgery, in order to provide a more effective treatment for mCRC patients. Through the design of a single-arm, single-center clinical study, we can have a deeper understanding of the efficacy and safety of this combined treatment in a specific patient population, providing a scientific basis for future clinical applications.

This first-in-human (FIH) dose-escalation and dose-validation/expansion study will assess KO-2806, a farnesyltransferase inhibitor (FTI), as a monotherapy and in combination, in adult patients with advanced solid tumors.

The goal of this clinical trial is to evaluate an AI-integrated Emotional Granularity Growth intervention (AI-EGG) designed to enhance resilience and improve quality of life in young and middle-aged colorectal cancer (CRC) survivors. Emotional granularity refers to the ability to clearly identify and differentiate subtle emotional experiences, which may help individuals regulate emotions more effectively and build resilience after cancer treatment. The main questions it aims to answer are: * Does the AI-EGG intervention improve resilience in CRC survivors compared with routine psychological care? * Does the intervention improve emotional granularity, emotion regulation ability, and quality of life? * Is the AI-EGG intervention feasible and acceptable for young and middle-aged CRC survivors? Researchers will compare the AI-EGG intervention group to a control group receiving routine psychological care and standard educational materials to see whether the intervention leads to better psychological outcomes. Participants will: * Complete baseline assessments measuring emotional granularity, emotion regulation, resilience, and quality of life * Be randomly assigned to either the intervention group or the control group * In the intervention group, engage in a 4-week AI chatbot-based program focusing on emotional identification, differentiation, regulation, and reflective practice (at least two sessions per week) * In the control group, receive routine psychological care and standard educational materials * Complete post-intervention assessments immediately after the 4-week program and again at a 1-month follow-up * Some participants in the intervention group will be invited to complete interviews about their experience of the program

This study is to evaluate the safety and tolerability of RMC-9805 as monotherapy and in combination with RMC-6236 in adults with KRAS G12D-mutant solid tumors.

This study is to evaluate the safety and tolerability of of LT-010391 as monotherapy in participants with KRAS G12D mutant advanced 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.

The purpose of this study is to evaluate the safety, tolerability, and efficacy of BMS-986523 alone and in combination with anti-cancer agents in participants with advanced solid malignancies

The goal of this clinical trial is to clarify the efficacy and safety of transcutaneous electrical acustimulation (TEA) in elderly patients with colorectal cancer, and to evaluate its clinical value in promoting postoperative intestinal function recovery and reducing the incidence of intestinal complications. The main questions it aims to answer are: Can TEA promote the recovery of intestinal function in elderly patients with colon cancer after surgery? What medical problems might occur to the participants when using TEA? The researchers will compare TEA with the control group (non-acupoint sham stimulation) to see if TEA is effective in promoting the recovery of intestinal function after surgery. Participants will: Starting from the first day after the surgery, they received TEA or sham stimulation twice a day for a total of 3 days. Record the time of the first defecation, defecation, and eating. Record their symptoms and adverse events.

This is an expanded access program (EAP) designed to provide access to Botensilimab and Balstilimab prior to drug registration by the applicable local regulatory agency. A medical doctor must decide whether the potential benefit outweighs the risk of receiving an investigational therapy based on the individual patient's medical history and program eligibility criteria.

Evaluate the safety and tolerability of RMC-6236 in adults with specific RAS mutant advanced solid tumors.

Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths globally, with increasing incidence rates. While predominantly affecting older adults, CRC cases among individuals under 50 (early-onset CRC, or EoCRC) are rising. This age group rarely undergoes routine screening, resulting in delayed diagnoses and more advanced disease at presentation. In the USA, EoCRC accounts for 10% of CRC cases and is the leading cause of cancer-related deaths in men under 50. Despite the increase in EoCRC incidence, the causes remain unclear. Only 25% of cases have a CRC family history, suggesting environmental factors. Diets low in fibre and rich in fat and red meat, obesity, alcohol consumption, sedentary lifestyle, stress, and chronic inflammation of the GI tract are estimated to account for 70-90% of CRC risk. According to the World Cancer Research Fund, 47% of all CRC cases could be prevented through lifestyle changes, particularly in diet and physical activity. These lifestyle factors are also strongly linked to changes in the gut microbiome, which differs markedly between CRC patients and healthy individuals. The microbiome may influence tumour development by producing metabolites that regulate immune responses or create anti-tumour environments. Thus, the gut microbiome is a promising target for early CRC detection and prevention. This study aims to develop a non-invasive, microbiome-based diagnostic tool for CRC, identifying biomarkers to improve early detection, personalise treatment, and reduce healthcare costs.

Colorectal cancer (CRC) is a major public health problem, responsible for 2 million new cases and almost 1 million deaths annually worldwide. In Portugal, as of 2022, CRC is the most common cancer, with 10,575 new cases reported, and the second leading cause of cancer-related mortality, accounting for 4,809 deaths (approximately 14% of all cancer-related deaths). In recent years, there has been an alarming increase in the incidence and mortality of CRC in people \<50 years of age. Early detection is crucial, as survival rates decline sharply from 90% when detected early to just 10% in advanced stages. Non-invasive diagnostic tests, such as the Faecal Immunochemical Test (FIT), have a low sensitivity for early-stage lesions and a high rate of false positives. Therefore, there is an urgent need to improve non-invasive diagnostic methods for the early detection of CRC, as effective screening can prevent it by detecting and removing premalignant lesions. Recent studies suggest that an altered gut microbiota may confer susceptibility to certain types of cancer. Interestingly, the gut microbiota of patients with adenomas or CRC differs from that of healthy individuals. This study aims to identify gut microbiome biomarkers in faecal samples associated with CRC and/or high-risk adenomas to improve early detection.

This study focuses exclusively on American Indian individuals within their communities to enhance health equity and address a critical tribal health priority. American Indian populations experience some of the highest colorectal cancer (CRC) mortality rates in the nation. By conducting research within these communities, this study aims to improve early detection, prevention, and treatment strategies tailored to their specific needs. The findings will help develop targeted interventions to reduce CRC disparities and improve health outcomes for American Indian individuals.

This is a prospective, open-label, randomized, parallel-group phase II trial evaluating the efficacy and safety of a low-dose radiotherapy sensitization strategy combined with a PD-1 antibody (pucotenlimab) and CAPEOX as neoadjuvant therapy in patients with pMMR/MSS locally advanced rectal adenocarcinoma. Participants will be randomized 1:1 to receive either 2 Gy or 5 Gy low-dose radiotherapy. Low-dose radiotherapy is delivered as a single fraction of 2 Gy (Arm A) or 5 Gy (Arm B). On the day after radiotherapy, participants will start pucotenlimab 200 mg IV Q3W (administered on Day 2 of each 21-day cycle) plus CAPEOX chemotherapy. Early response will be assessed after 2 cycles using endoscopy and pelvic MRI to guide subsequent treatment: participants with partial response may discontinue radiotherapy and continue neoadjuvant systemic therapy; participants with stable disease may switch to standard chemoradiotherapy; participants with progressive disease will receive multidisciplinary-team-guided salvage therapy. After 4 cycles, participants with clinical complete response may adopt a watch-and-wait strategy; otherwise, they will undergo radical surgery 2-4 weeks after completion of neoadjuvant therapy. Long-term follow-up will include recurrence and survival outcomes and quality of life.

This study will utilize ctDNA methylation detection to evaluate patients with stage I or low-risk stage II colorectal cancer who are ctDNA-positive one month after surgery. It aims to investigate the impact of different adjuvant chemotherapy regimens on ctDNA clearance rates and their prognostic significance. By using postoperative ctDNA status to identify patients at high risk of recurrence, the study seeks to implement intensified chemotherapy strategies (treatment escalation) at an early stage, thereby improving ctDNA clearance and ultimately enhancing patient outcomes.

The goal of this study is to learn if KQB368 works to treat advanced solid malignancies in adults. The study will also learn about the safety of KQB368. The main questions the study aims to answer are: * What is the safe dose of KQB368 as a monotherapy? * Does KQB368 decrease the size of the tumor? * What happens to KQB368 in the body? Participants will: * Take KQB368 orally daily in 21-day cycles * Return to the study site about 7 times in the first 5 weeks, and then once at the beginning of every 21-day cycle after that