Metastatic Colorectal Cancer (CRC)

A Randomized, Active-Controlled, Double-blind, Multicenter, Phase 3 Clinical Study of Ivonescimab in Combination with mFOLFOX6 (Oxaliplatin, Leucovorin and 5-Fluorouracil) versus Bevacizumab in Combination with FOLFOX for the First-line Treatment of Metastatic Colorectal Cancer(HARMONi-GI3)

This is a prospective, multicenter, randomized controlled, phase II study. It is expected to enroll 229 patients and aims to evaluate the efficacy and safety of FOLFOX8 versus mFOLFOX6 combined with bevacizumab or cetuximab as first-line treatment for unresectable metastatic colorectal cancer. The primary objective is to assess progression-free survival (PFS) of the patients. Secondary objectives include assessment of objective response rate (ORR), overall survival (OS), safety, and other outcomes.

To learn if SAR445877 in combination with FOLFOX6 and bevacizumab can be safely given to patients with advanced MSS CRC.

A first in human study to evaluate the safety and preliminary antitumor activity of BBO-11818, a pan-KRAS inhibitor, in subjects with locally advanced unresectable or metastatic KRAS mutant solid tumors.

This study is a prospective, single-arm, multicenter exploratory clinical study aimed at evaluating the efficacy and safety of Fruquintinib combined With Serplulimab and chemotherapy as first-line treatment for RAS/BRAF-mutated unresectable advanced colorectal cancer. The study plans to enroll 80 patients with RAS/BRAF-mutated unresectable advanced metastatic colorectal cancer. After evaluation and confirmation of meeting enrollment criteria, patients will receive treatment with Fruquintinib combined With Serplulimab and chemotherapy . The primary endpoint of the study is PFS, and secondary endpoints include ORR, DCR, OS, and safety.

The main objective of this study is to identify the prognostic factors (clinico-biological) for the efficacy (overall survival) of fruquintinib in patients with metastatic colorectal cancer.

This is a phase 1, open-label, multicentric study evaluating the safety, feasibility and efficacy of ODI-2001, a personnalized therapeutic cancer vaccine composed of DNA neoantigen vaccine, Modified Vaccinia virus Ankara (MVA) viral adjuvant and anti-CTLA4 (ipilimumab), in patients with metastatic or locally advanced colorectal or pancreatic cancer. The study includes a dose-escalation phase to determine the maximum tolerated dose (MTD) followed by an expansion phase to evaluate efficacy in terms of progression-free survival

Phase II - Treatment Regimen Exploration Stage: 1. Evaluate the safety and efficacy of the following three treatment regimens: Liposomal irinotecan + 5-FU/LV + bevacizumab + Enlonstobart (Group A) Liposomal irinotecan + 5-FU/LV + bevacizumab (Group B) Irinotecan + 5-FU/LV + bevacizumab (Group C) 2. Provide a basis for selecting the treatment regimen for the confirmatory phase. 3. Explore the relationship between tumor tissue, stool, and blood biomarkers and efficacy and adverse reactions in liposomal irinotecan combination regimens versus irinotecan combination regimens. Phase III - Efficacy Confirmation Stage: Compare the efficacy and safety of liposomal irinotecan combination regimens versus irinotecan combination regimens in second-line treatment of metastatic colorectal cancer.

This study is a prospective, single-arm, multicenter exploratory clinical study aimed at evaluating the efficacy and safety of iparomlimab and tuvonralimab combined with bevacizumab and alternating triweekly CAPOX/mCAPIRI regimen as first-line treatment for unresectable advanced colorectal cancer. The study plans to enroll 70 patients with unresectable advanced metastatic colorectal cancer. After evaluation and confirmation of meeting enrollment criteria, patients will receive treatment with iparomlimab and tuvonralimab combined with bevacizumab and alternating triweekly CAPOX/mCAPIRI regimen. The primary endpoint of the study is ORR, and secondary endpoints include PFS, DoR, OS, and safety.

This is an observational, retrospective, international and multicenter study funded by Fondazione Oncologia Niguarda ETS to assess the efficacy of anti-EGFR rechallenge regimens in the largest real-world cohort of MSS mCRC patients screened for RAS/BRAF/PIK3CA ctDNA status on liquid biopsy within the MEN1611-02 C-PRECISE-01 trial. The study will collect molecular, clinical and outcome data of patients already available at participating centers.

This Phase II clinical trial at Houston Methodist Neal Cancer Center is evaluating the safety and efficacy of combining 5-Fluorouracil (5FU) -based chemotherapy (either FOLFIRI: folinic acid, 5FU, irinotecan; or mFOLFOX6: folinic acid, 5FU, oxaliplatin) with fruquintinib as a first-line treatment for patients with locally advanced unresectable or metastatic colorectal cancer. Fifty patients will receive treatment in 28-day cycles, with fruquintinib initially dosed at 4 mg daily and potentially increased to 5 mg if no significant toxicities are observed. After six months, patients showing stable disease or better will transition to a maintenance phase with 5FU and fruquintinib, continuing until disease progression or other discontinuation criteria are met. The primary endpoint is time to progression based on RECIST v1.1 criteria, while secondary endpoints include safety, tolerability, and duration of response. The trial is being conducted across multiple Houston Methodist hospitals and is currently the only first-line CRC trial available in the system. If successful, it could offer a new therapeutic option and inform future treatment guidelines for advanced colorectal cancer.

The primary objective of this study is to evaluate the feasibility, safety, and efficacy of personalized T-cell therapy based on tumor neoantigens in patients with advanced colorectal cancer, so as to provide a novel individualized therapeutic strategy for such patients.

This is a randomized, parallel, open-label, multicenter exploratory clinical study designed to investigate the efficacy and safety of iparomlimab and tuvonralimab in combination with fruquintinib plus heterogeneous radiotherapy, compared with fruquintinib monotherapy, as the third-line and subsequent-line treatment for patients with oligometastatic colorectal cancer.

A single-arm, open-label clinical study of irinotecan liposome combined with capecitabine, bevacizumab and camrelizumab as second-line or above treatment for patients with metastatic colorectal cancer, aiming to evaluate the efficacy and safety of irinotecan liposome combined with capecitabine, bevacizumab and camrelizumab as second-line or above treatment for patients with metastatic colorectal cancer The medication regimen is irinotecan liposome (II) + capecitabine + bevacizumab + camrelizumab until disease progression or intolerable toxicity.

This study is a phase II, open-label, multicenter clinical trial designed to evaluate two different treatment options for patients with metastatic colorectal cancer whose disease has progressed after standard therapies. The study compares a rechallenge treatment using irinotecan plus cetuximab with the current standard of care, trifluridine/tipiracil plus bevacizumab, as third-line therapy. Patients enrolled in the study are selected based on specific molecular characteristics of their cancer, identified through circulating tumor DNA analysis from a blood sample. The main purpose of the study is to determine whether the rechallenge with irinotecan and cetuximab leads to a higher tumor response rate compared with trifluridine/tipiracil plus bevacizumab. Secondary objectives include evaluating progression-free survival, overall survival, safety, and quality of life. Patients will be randomly assigned to one of the two treatment groups and will receive treatment until disease progression, unacceptable side effects, or withdrawal of consent. Tumor response will be assessed using standard imaging techniques according to RECIST criteria.

Fruquintinib, as a standard treatment for refractory metastatic colorectal cancer (mCRC), has attracted increasing research efforts to explore its innovative strategies in combination with chemotherapy. Trifluridine/tipiracil plus bevacizumab is also a standard treatment for mCRC. This study aims to explore the efficacy and safety of fruquintinib combined with trifluridine/tipiracil versus bevacizumab combined with trifluridine/tipiracil in the treatment of patients with advanced metastatic colorectal cancer who failed standard chemotherapy.

To explore the safety and efficacy of NALIRIFOX plus targeted therapy versus FOLFOX plus targeted therapy as first-line treatment for metastatic colorectal cancer.

This study is a multicenter, open-label, phase II clinical trial evaluating the combination of SSGJ-706 with standard therapy for advanced gastrointestinal tumors. Its objective is to assess the safety, tolerability, and antitumor activity of SSGJ-706 in combination with standard treatment.

This is a pilot, prospective, randomized study evaluating the feasibility and acceptability of incorporating hemp-derived cannabidiol (CBD) supplementation to prevent oxaliplatin-induced peripheral neuropathy (OIPN) in patients receiving oxaliplatin-based chemotherapy for colorectal cancer (CRC). Participants will be randomized to receive either CBD capsules in addition to standard therapy or standard therapy alone.

This is a non-inferiority randomized phase II trial investigating the efficacy and safety of 5FU/LV in combination with regorafenib for patients with metastatic colorectal cancer in the third-line setting. Patients will be randomly assigned in a 2:1 ratio between 5FU/LV combined with regorafenib or trifluridine-tipiracil (FTD-TPI) plus bevacizumab. Arm 1 (Treatment Arm) will consist of the 5FU/LV administered to 38 patients as (LV \[400 mg/m² IV over 120 minutes\], followed by 5FU \[400 mg/m² IV bolus then 2400 mg/m² IV infusion over 46 hours\] in 2-week cycles) and regorafenib will be administered dose of 80-120 mg per day with weekly 40 mg per day increases to a maximum of 120 mg per day for 3 weeks on /1 week off until disease progression, up to 12 cycles of treatment. Arm 2 (Control Arm) received by an additional 19 patients, will be given as FTD-TPI, administered orally, BID, at a starting dose of 35 mg/m2 of body-surface area, on days 1 through 5 and on days 8 through 12 every 28 days. Bevacizumab, at a dose of 5 mg per kilogram of body weight, will be administered intravenously on days 1 and 15. The 28-day treatment cycle continued until disease progression or unacceptable toxic effects occurred or consent was withdrawn, up to 12 cycles of treatment.

This study is a randomized, controlled, open-label, phase II clinical study. This study is designed to evaluate the efficacy and safety of second-line standard treatment sequential TAS-102 and bevacizumab combined with local treatment versus continuous treatment of standard second-line therapy in advanced colorectal cancer.

The current standard first-line treatment for metastatic colorectal cancer is chemotherapy combined with targeted therapy, yet the prognosis remains poor. Although combining immunotherapy, anti-angiogenic agents, and chemotherapy has shown some efficacy in MSS/pMMR metastatic patients, progression-free survival (PFS) remains suboptimal. Radiotherapy-particularly high-dose radiotherapy-can enhance tumor antigen release and potentially improve the response of MSS/pMMR colorectal cancer to PD-1 inhibitors. Tumor-draining lymph nodes (TDLNs) are key sites for PD-1-mediated anti-tumor activity, but radiation-induced damage and fibrosis may impair their immune function. Prior studies have reported a remarkable pathologic complete response (pCR) rate of 77.8% using node-sparing radiotherapy in locally advanced rectal cancer. This phase II/III study aims to evaluate whether node-sparing modified short-course radiotherapy combined with chemotherapy, bevacizumab, and PD-1 blockade can improve objective response rate (ORR) in phase II and progression-free survival (PFS) in phase III, together with treatment tolerance, and overall prognosis in patients with pMMR/MSS metastatic colorectal cancer.

The objective of this multi-center, single-group, open-label Phase Ib/II study is to evaluate the safety, pharmacokinetics, and efficacy of nelmastobart in combination with trifluridine/tipiracil and bevacizumab in metastatic or recurrent colorectal cancer patients with resistance or intolerance to oxaliplatin- and irinotecan-based chemotherapy, and to determine the maximum tolerated dose (MTD), recommended Phase 2 dose (RP2D), and the efficacy and safety of the combination therapy in BTN1A1-positive patients.

This is a single-arm, multi-center, exploratory study evaluating the efficacy and safety of iparomlimab and tuvonralimab (QL1706) in combination with bevacizumab for the treatment of patients with microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) unresectable or metastatic colorectal cancer. Eligible participants who meet the inclusion and exclusion criteria will provide written informed consent and receive QL1706 at 5.0 mg/kg and bevacizumab at 7.5 mg/kg on Day 1 of every 3-week cycle (Q3W), until disease progression or completion of 2 years of treatment. The primary endpoint of this study is objective response rate (ORR). Secondary endpoints include disease control rate (DCR), duration of response (DoR), progression-free survival (PFS), overall survival (OS), PFS and OS rates at 6, 12, and 24 months, and safety.

This is a prospective randomized controlled Phase Ⅱ/Ⅲ Clinical study to evaluate the clinical efficacy and safety of Envafolimab combining with Cetuximab -β and mFOLFOX6 in Patients With MSS, RAS/BRAF Wild-Type Metastatic Colorectal Cancer (mCRC)