Clinical Research Directory

KO-2806 Monotherapy and Combination Therapies in Advanced Solid Tumors

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.

GEN1042 Safety Trial and Anti-tumor Activity in Participants With Malignant Solid Tumors

The goal of this trial is to learn about the antibody GEN1042 when it is used alone and when it is used together with another antibody cancer drug, pembrolizumab (with or without chemotherapy), for treatment of participants with certain types of cancer.

Dose Escalation and Dose Expansion Study of RMC-6291 Monotherapy in Subjects With Advanced KRASG12C Mutant Solid Tumors

The purpose of this study is to evaluate the safety, tolerability, and pharmacokinetics (PK) of escalating doses of RMC-6291 (KRAS G12C(ON) inhibitor) monotherapy in adult subjects with advanced solid tumors and to identify the maximum tolerated dose (MTD), and the recommended Phase 2 dose.

Raising Awareness of Colorectal Screening in American Indian Communities

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.

Advanced Therapies for Liver Metastases

Liver metastases (MTS) are the main cause of death for patients affected by colorectal carcinoma (CRC) and pancreatic ductal adenocarcinoma (PDAC), thus representing the major unmet clinical need for these malignancies. Based on preliminary and published data, the investigators hypothesize that innovative immune, gene, and cell therapy approaches might overcome the tolerogenic liver microenvironment and represent powerful therapeutic tools for liver MTS of PDAC and CRC. The investigators have therefore planned an observational clinical study to enroll distinct cohorts of patients (i.e., metastatic CRC, preneoplastic, metastatic, and non-metastatic PDAC) and finely characterize, through integrated state-of-the-art -omics, the immune and non-immune microenvironment of their primary tumor and/or liver metastases as well as correlate changes in the activation status and phenotype of peripheral blood leukocytes. Healthy volunteers will be enrolled as negative controls. The investigators aim at identifying: i) actionable tumor-associated antigens (TAAs) and local immune suppressive and regulatory pathways; ii) biological parameters for early diagnosis of relapse; iii) the effect of therapies on the shaping of anti-tumor immune responses. Data collected will be instrumental for the generation of novel advanced therapy medicinal products (ATMPs). Indeed, this protocol is part of a multi-partner translational program, supported by the AIRC 5 per Mille 2019 grant, focused on the development, validation, and implementation of clinical testing for ATMPs to ameliorate the cure of CRC and PDAC, and possibly to help the study of other solid tumors. Moreover, the systematic and long-term follow-up of enrolled patients will possibly point to early predictors of differential prognosis and patients' categories eligible for tailored therapies, including those with the novel ATMPs. In this regard, two additional substudies were incorporated into the main LiMeT protocol in July 2024 and January 2026, respectively, supported by supplementary funding: 1) the TREATLIVMETS (Treating Liver Metastasis) project, funded by the European Research Council (ERC) under the Horizon Europe research and innovation program; 2) the "Deciphering and targeting the immunological niche in PDAC" project, funded by the Fondazione Regionale per la Ricerca Biomedica (FRRB) under the "From Bed to Bench 2024" call. In the latter substudy, machine learning will be integrated with the spatial multi-omic profiling of the immune landscape in preneoplastic and neoplastic lesions in a subset of IPMN and PDAC patients, supporting the discovery of new therapeutic targets and enabling the early detection of preneoplastic lesion progression.

Study of RAS(ON) Inhibitors in Combination With Ivonescimab in Patients With Solid Tumors

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.

A Study of Fruquintinib Plus FOLFIRI as Second-Line Treatment for Participants With Metastatic Colorectal Cancer (mCRC)

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

A Study 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 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

Study of Zanzalintinib in Combination With Immuno-Oncology Agents in Participants With Solid Tumors

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.

Study of BPI-572270 in Patients With Advanced Solid Tumors Harboring Specific Mutations in RAS

Evaluate the safety and tolerability of BPI-572270 in adult patients with specific RAS mutant advanced solid tumors.

Safety and Efficacy of Tegavivint in Patients With Metastatic Colorectal Carcinoma

This trial will evaluate the safety, tolerability, and preliminary efficacy of tegavivint as monotherapy (single) and in combination with standard therapies in patients with metastatic colorectal carcinoma (mCRC).

Study of JYP0015 in Patients With Advanced Solid Tumors Harboring Specific Mutations in RAS

Evaluate the safety and antitumor activity of JYP0015 in adults with specific RAS mutant advanced solid tumors.

Low-Dose Radiotherapy to Sensitize Pucotenlimab Plus CAPEOX for pMMR Locally Advanced Rectal Cancer

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.

A Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Anti-tumor Activity of CBI-1214 T Cell Engager in Participants With Advanced or Metastatic MSS/MSI-L Colorectal Cancer

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

Lubiprostone Combined With Maintenance Therapy for Prevention of Postoperative Recurrence in Peritoneal Metastatic Colorectal Cancer

The goal of this phase II randomized controlled clinical trial is to evaluate whether adding lubiprostone to standard postoperative maintenance therapy can delay disease progression and recurrence in adult patients with colorectal cancer and peritoneal metastases (PM-CRC) who have undergone cytoreductive surgery with or without HIPEC after systemic treatment. The main questions it aims to answer are: Does lubiprostone plus maintenance therapy improve the 1-year progression-free survival (PFS) rate compared with maintenance therapy alone? Is lubiprostone safe and feasible for long-term use during the maintenance period in this PM-CRC population? Researchers will compare lubiprostone + maintenance therapy versus maintenance therapy alone to see if the addition of lubiprostone prolongs PFS, reduces the risk of distant metastasis, improves overall survival, and maintains or improves quality of life. Participants will: Be randomly assigned to receive maintenance therapy with lubiprostone or maintenance therapy alone after surgery (CRS ± HIPEC) and prior systemic therapy, according to the study protocol. Undergo scheduled follow-up assessments for disease status (progression/recurrence), survival outcomes, treatment-related toxicity, and quality of life using the EORTC QLQ-C30 (v3.0) questionnaire.

Sotorasib and Panitumumab Versus Investigator's Choice for Participants With Kirsten Rat Sarcoma (KRAS) p.G12C Mutation

The aim of the study is to compare progression-free survival (PFS) in previously treated participants with Kirsten rat sarcoma (KRAS) p.G12C mutated colorectal cancer (CRC) receiving sotorasib 240 mg once daily (QD) and panitumumab vs investigator's choice (trifluridine and tipiracil, or regorafenib), and sotorasib 960 mg QD and panitumumab vs investigator's choice (trifluridine and tipiracil, or regorafenib).

Study of RMC-5127 in Patients With Advanced KRAS G12V-Mutant 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.

Reduce Sedentary Behavior During Cancer Treatment - the RedSedCan Study

Summary Reducing sedentary behavior during treatment is important to reduce the risk of future health problems in individuals undergoing cancer treatment. Therefore, the goal of this project is with a multicenter randomised controlled design investigate whether a digital support intervention during ongoing neo- or adjuvant cancer treatment for breast, prostate or colon cancer is effective in reducing sedentary lifestyle and improving well-being in the short and long term.

Phase 1/2 Study to Evaluate TH9619 in the Treatment of Advanced Solid Tumors

This is a first in human, multi-center, open-label, dosage escalation study to determine the recommended dose range of TH9619 in subjects with advanced cancer.

Faecal Immunochemical Tests (FIT) for Surveillance After Colorectal Cancer (CRC) Study

In the United Kingdom, over 25,000 patients have an operation for bowel cancer each year. After their operation, patients are monitored with a colonoscopy (camera test of the bowel) approximately 3 years after their operation, to look for any possible return of the cancer. Colonoscopies, and the bowel-cleaning medications needed, can be unpleasant for patients. The Faecal Immunochemical Test (FIT) is a test to look for blood hidden in the poo. Blood in the poo can be a sign of bowel cancer, or a growth that can turn in to a cancer if left untreated (polyps). We currently use this test for bowel cancer screening, and to assess the risk of cancer in patients with bowel symptoms. You may have had a FIT when having tests for bowel cancer. We know this test is effective in picking up bowel cancer in these cases, but its use has not been assessed in following-up patients who have had treatment for bowel cancer previously. For this study, we aim to see if a FIT stool sample test is accurate at diagnosing a return of bowel cancer for patients who have had a previous operation for bowel cancer. We want to see if using FIT could 'rule-out' cancer for some patients and be a potential alternative to colonoscopy for some patients in the future, allowing them to avoid this sometimes unpleasant test, which patient groups have told us is important for them. Patients taking part in this study will have their usual treatment, including their colonoscopy (or sometimes a scan of the bowel), but will be asked to also provide a single FIT sample to assess how accurate this test is. The FIT sample is a quick and easy test of the poo that you can take at home and send to Nottingham University Hospitals NHS Trust (NUH) for testing. It should take no more than 5 to 10 minutes to take the sample, and a prepaid envelope is included to send the sample back to NUH for testing. We aim to include at least 1,000 patients across 7 hospital trusts in the East Midlands.

Exploring the Effects of Magnesium Ions on Peripheral Neuropathy, Serum Magnesium Ion Concentration,Sleep Quality, and Quality of Life in Patients With Colorectal Cancer Receiving Chemotherapy.

Chemotherapy for colorectal cancer (CRC) is frequently complicated by chemotherapy-induced peripheral neuropathy (CIPN) and impaired sleep quality, significantly impacting patient quality of life. Low magnesium levels have been implicated in peripheral nerve dysfunction. This interventional study aims to investigate the effects of magnesium supplementation on serum magnesium concentration, CIPN severity, and sleep quality in CRC patients undergoing chemotherapy. Study Design and Methods This is a prospective, parallel-group, randomized controlled trial (RCT) utilizing a longitudinal design. Participants (CRC patients undergoing chemotherapy) will be randomly allocated to one of three groups: * Experimental Group 1: Oral magnesium (400mg) supplementation. * Experimental Group 2: Oral magnesium (400mg}) supplementation and magnesium solution foot baths. * Control Group: Standard care. Measurements will be collected using structured questionnaires and blood samples during each chemotherapy cycle. The primary outcomes will be assessed using: * Serum Magnesium Concentration * CIPN Severity: Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-neurotoxicity (FACT/GOG-Ntx) scale. * Sleep Quality: Verran and Snyder-Halpern Sleep Scale (VSH). Primary Research Questions (Hypotheses) 1. Can the magnesium intervention (oral and/or foot baths) effectively increase the serum magnesium concentration in CRC patients? 2. Can the magnesium intervention alleviate or improve the severity of CIPN? 3. Can the magnesium intervention improve the sleep quality of CRC patients during chemotherapy? The intervention groups will be compared against the control group to determine if the magnesium interventions lead to superior improvement in the measured outcomes.

Injection of IP-001 Into Thermally Ablated Hepatic Tumors in Patients With Colorectal Liver Metastases

The goal of this clinical trial is to learn if a new injectable drug (IP-001), administered after standard liver tumor ablation, can help prevent cancer from returning in people (males/females, ≥18 years old) with colorectal cancer that has spread only to the liver. The study will determine if injecting IP-001 into a liver tumor(s) after ablation will reduce the risk of cancer coming back in the liver and from spreading elsewhere in the body, will stimulate the immune system, will have any side effects, and will help improve a patient's response to other cancer therapies. Researchers will compare a standard of care liver ablation alone (microwave ablation \[MWA\], a technique that destroys tumors using heat), with MWA plus a high-dose IP-001 or MWA with a low-dose IP-001. During the treatment procedures, the doctor first performs the standard microwave ablation to destroy the tumor. Then, in the experimental-drug arms, IP-001 is injected in and around the treated tumor area to activate the immune system locally so that the body is more likely to find and eliminate any remaining cancer cells.

mFOLFOX6 + Bevacizumab + PD-1 Monoclonal Antibody Vs. mFOLFOX6 in Locally Advanced pMMR/MSS CRC

Neoadjuvant immunotherapy has shown promising therapeutic effects in mismatch repair-deficient or microsatellite instability-high (dMMR/MSI-H) colorectal cancer (CRC). However, for patients with mismatch repair-proficient or microsatellite stable (pMMR/MSS) CRC, the efficacy of PD-1 monoclonal antibody remains limited. Enhancing the efficacy of immunotherapy in pMMR/MSS CRC has become a key area of exploration. Additionally, for locally advanced (cT4NxM0) CRC patients, achieving R0 resection poses a significant challenge. Failure to achieve R0 resection often results in recurrence, severely impacting patient survival outcomes. Our previous phase II clinical study (BASKET Ⅱ) demonstrated that the neoadjuvant regimen of mFOLFOX6 combined with Bevacizumab and PD-1 monoclonal antibody significantly enhanced the immunotherapy sensitivity of locally advanced pMMR/MSS CRC, leading to improved pathological complete response (pCR) rates and higher R0 resection rates. This prospective, multicenter, randomized phase III trial aims to evaluate whether the neoadjuvant regimen of mFOLFOX6 + Bevacizumab + PD-1 monoclonal antibody can further improve pCR rate, enhance survival outcomes, and maintain an acceptable safety profile compared to mFOLFOX6 alone in pMMR/MSS locally advanced CRC patients.

An Open-Label Study to Enable Continued Treatment Access for Subjects Previously Enrolled in Studies of Ruxolitinib

The purpose of this study is to provide continued supply of ruxolitinib alone, ruxolitinib plus background cancer therapy, or background cancer therapy alone to subjects from an Incyte-sponsored study of ruxolitinib that has reached its study objectives or has been terminated. This study will also provide another mechanism for reporting adverse events related to study drug safety.