Lonsurf (trifluridine/tipiracil)

P1/2, N=70, Not yet recruiting, STCube, Inc.

P2, N=33, Not yet recruiting, Sir Run Run Shaw Hospital

P2, N=126, Recruiting, Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest | Not yet recruiting --> Recruiting | Initiation date: Dec 2024 --> Mar 2025

P2, N=140, Not yet recruiting, Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest

P2, N=119, Recruiting, Fudan University

Adult patients at least 18 years old diagnosed with hormone receptor positive, HER2- receptor negative MBC with a performance status of 0 or 1 who have been treated with capecitabine in the metastatic setting and up to two other lines of chemotherapy, including a taxane, were enrolled in this single-arm, multicentre, phase 2 study in the Netherlands. Preparations for a phase 3 trial are underway. Servier, France.

P3, N=228, Not yet recruiting, Shandong Cancer Hospital and Institute

The findings indicated that initiating treatment with regorafenib followed by FTD-TPI had superior clinical outcomes compared with the reverse sequence among mCRC patients. This study offers real-world evidence for clinical decision-making and treatment optimization.

P1, N=520, Active, not recruiting, AbbVie | Recruiting --> Active, not recruiting

P1, N=19, Active, not recruiting, OHSU Knight Cancer Institute | Trial completion date: Dec 2024 --> May 2025

Based on a critical review of the literature aimed to guide clinicians in their daily decision-making, we point out that the combination of FTD/TPI with bevacizumab produces a clinical benefit in unselected mCRC patients. Therefore, the FTD/TPI plus bevacizumab regimen can represent a new standard of care for the treatment of patients with refractory mCRC who have progressed after two lines of therapy.

P2, N=22, Active, not recruiting, Roswell Park Cancer Institute | Trial completion date: Dec 2024 --> Dec 2025

P2, N=36, Recruiting, Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori | Active, not recruiting --> Recruiting

Pembrolizumab may be less effective than FTD/TPI in later-line treatment of MSS-TMB-H mCRC, potentially due to genomic similarities between MSS-TMB-H and MSS-TMB-L CRC, suggesting the need for alternative therapeutic strategies in this subgroup.

P3, N=160, Active, not recruiting, Amgen | Trial completion date: Mar 2025 --> Jun 2025

P4, N=283, ShangHai ChangHai Hospital; ShangHai ChangHai Hospital

P2, N=20, Hebei General Hospital; Hebei General Hospital

P2, N=30, Zhejiang Cancer Hospital; Zhejiang Cancer Hospital

P2, N=52, Mianyang 404 Hospital; Sichuan Mianyang 404 Hospital

XB2001, a fully human monoclonal antibody neutralizing IL-1α, was evaluated for safety and preliminary efficacy with trifluridine/tipiracil (FTD/TPI) and bevacizumab in metastatic colorectal cancer patients previously treated with oxaliplatin- and irinotecan-based chemotherapies. High intratumoral IL-1α expression at baseline and CD8/PD-L1 infiltration are associated with a better progression-free survival. The combination of XB2001 with FTD/TPI and bevacizumab is feasible and safe, and showed encouraging clinical activity in chemotherapy-resistant mCRC.

P1/2, N=48, Active, not recruiting, Gruppo Oncologico del Nord-Ovest | Trial primary completion date: Dec 2024 --> May 2024

P2, N=36, Active, not recruiting, Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori | Not yet recruiting --> Active, not recruiting | Initiation date: Sep 2024 --> Jan 2025

Our data show that treatment with FTD/TPI offers survival benefits in patients with refractory mCRC in Hong Kong consistent with randomized controlled trials and other real-world studies. Furthermore, the prognosis in patients receiving FTD/TPI appears to be significantly better in those who develop neutropenia, with RAS wild-type status, or those without liver metastases, despite a higher rate of dose reduction in the real-world setting.

P2, N=100, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Aug 2024 --> Aug 2026 | Trial primary completion date: Aug 2024 --> Aug 2026

P2, N=57, Not yet recruiting, Sun Yat-sen University

P1/2, N=64, Active, not recruiting, Emory University | Recruiting --> Active, not recruiting | Trial primary completion date: Nov 2024 --> Jun 2025

P1/2, N=75, Active, not recruiting, Yonsei University | Recruiting --> Active, not recruiting

P1/2, N=75, Recruiting, Yonsei University | Not yet recruiting --> Recruiting | Phase classification: P2 --> P1/2

P1/2; Trial completion date: Dec 2027 --> May 2028 | Trial primary completion date: Dec 2027 --> May 2028

P3, N=700, Active, not recruiting, Bristol-Myers Squibb | Trial completion date: May 2028 --> Jul 2025 | Trial primary completion date: Jan 2025 --> Jul 2025

P3, N=856, Active, not recruiting, Institut de Recherches Internationales Servier | Trial completion date: Jun 2024 --> Dec 2025

P1/2, N=480, Recruiting, Parabilis Medicines, Inc. | N=245 --> 480

"The abstract will be released to the public on January 21, 2025 at 10:00 PM UTC"

P2, N=73, Not yet recruiting, UNICANCER | Initiation date: Oct 2024 --> Jan 2025

P=N/A, N=200, Enrolling by invitation, Helsinki University Central Hospital | Trial completion date: Dec 2025 --> Dec 2027 | Trial primary completion date: Dec 2020 --> Dec 2027

P2, N=60, Not yet recruiting, CytoDyn, Inc.

P3, N=460, Recruiting, AbbVie | Not yet recruiting --> Recruiting

Over the past decade, regorafenib and trifluridine-tipiracil were the only available drugs and often provided limited clinical benefit compared to best supportive care. Results from subsequent practice-changing trials opened several novel therapeutic avenues, both for unselected patients (such as trifluridine-tipiracil plus bevacizumab or fruquintinib) and for subgroups defined by the presence of actionable alterations in their tumours (such as HER2-targeted therapies or KRASG12C inhibitors) or with no acquired mechanisms of resistance to the previously received targeted agents in circulating tumour DNA (such as retreatment with anti-EGFR antibodies). In this Review, we provide a comprehensive overview of advances in the field over the past few years and offer a practical perspective on translation of the most relevant results into the daily management of patients with metastatic colorectal cancer using an evidence-based algorithm. Finally, we discuss some of the most appealing ongoing areas of research and highlight approaches with the potential to further expand the therapeutic armamentarium.

P2, N=50, Active, not recruiting, Rutgers, The State University of New Jersey | Trial completion date: Mar 2024 --> Mar 2026

We aim to assess the addition of XB2001 (anti-IL-1 alpha monoclonal antibody) plus trifluridine/tipiracil-bevacizumab in mCRC refractory to standard chemotherapy. This multicenter, randomized, double blind, non-comparative Phase I-II study (ClinicalTrials.gov NCT05201352) will assess the efficacy and safety of trifluridine/tipiracil-bevacizumab and XB2001 in patients with mCRC previously treated for metastatic disease by chemotherapy treatment including oxaliplatin, irinotecan, 5-FU, antiangiogenic and/or anti-EGFR if indicated...Primary end point of Phase II is the efficacy of trifluridine/tipiracil-bevacizumab + XB2001 in term of 6-month overall survival. Ancillary analysis will be performed.

P4, N=200, Not yet recruiting, The First Affiliated Hospital of Wenzhou Medical University; The First Affiliated Hospital of Wenzhou Medical University

P4, N=30, Not yet recruiting, The First Affiliated Hospital of Zhengzhou University; The First Affiliated Hospital of Zhengzhou University