Table of contents
- Clinical trials overview
- Colorectal cancer studies
- Other gastrointestinal cancer studies
- Special patient groups and biomarker-based studies
- Main study endpoints
- Trial phases and study design
Clinical trials overview
These studies investigate Trifluridine mainly in cancer treatment plans for people with advanced, metastatic, or hard-to-treat disease.[1] Most trials are in colorectal cancer, but there are also studies in gastric, gastroesophageal junction, oesophageal, cholangiocarcinoma, gallbladder, and breast cancer.[2][3]
Many trials test Trifluridine as part of a combination treatment, meaning it is given together with other cancer medicines such as bevacizumab, irinotecan, oxaliplatin, panitumumab, or fruquintinib.[4][5] Some studies compare a Trifluridine-based plan with another standard treatment, while others compare two Trifluridine-based schedules or add Trifluridine after another treatment step.[6][7]
Colorectal cancer studies
Colorectal cancer is the main area of research for Trifluridine in the trial data.[1][8] Several studies look at metastatic colorectal cancer, which means cancer that has spread beyond the colon or rectum.[9]
One Phase 2 study in metastatic colorectal cancer is testing a biomarker-driven cetuximab-based treatment plan over three treatment lines in patients with RAS/BRAF wild-type tumors at the start of first-line therapy, with response rate as the main outcome.[1] Another Phase 2 trial is comparing bevacizumab plus bi-weekly Trifluridine/tipiracil with a conventional schedule, and it focuses on grade 3-4 neutropenia, which is a serious drop in infection-fighting white blood cells.[2]
Other colorectal studies include a randomized Phase 2 trial in refractory metastatic colorectal cancer with liver-dominant disease, where Trifluridine/tipiracil plus bevacizumab is compared with melphalan/HDS followed by the same combination.[4] A Phase 2 study also examines Trifluridine/tipiracil plus panitumumab versus Trifluridine/tipiracil plus bevacizumab as first-line treatment for patients who are not candidates for intensive therapy.[10]
In later-line metastatic colorectal cancer, a Phase 3 study compared relatlimab-nivolumab fixed-dose combination with regorafenib or TAS-102, and another Phase 3 study compared sotorasib plus panitumumab against investigator’s choice, which could include Trifluridine/tipiracil or regorafenib.[7][8] These studies help show how Trifluridine is used as part of standard options in difficult-to-treat disease.
There is also a Phase 3 study in first-line metastatic colorectal cancer for people not fit for intensive therapy, comparing S 95005 plus bevacizumab with capecitabine plus bevacizumab, where Trifluridine appears in the treatment list as part of the study background.[11] Another Phase 3 study looked at MK-4280A versus standard care, where standard care included regorafenib or TAS-102, in colorectal cancer that had spread after previous treatment.[12]
Other gastrointestinal cancer studies
Several trials study Trifluridine in cancers of the stomach and nearby organs.[2][3] One Phase 2 study in HER2-negative advanced, recurrent, or metastatic gastric, oesophageal, or gastroesophageal junction adenocarcinoma compares trifluridine/tipiracil plus oxaliplatin, with or without nivolumab, against FOLFOX-based treatment, with progression-free survival as the main endpoint.[3]
A Phase 3 trial in metastatic oeso-gastric adenocarcinoma compares trifluridine/tipiracil plus fruquintinib with trifluridine/tipiracil alone, and its main endpoint is overall survival.[5] Another Phase 3 study in advanced or metastatic gastric, gastroesophageal junction, or esophageal adenocarcinoma compares MK-2870 with Trifluridine-containing standard treatment, again using overall survival as the key outcome.[13]
In cholangiocarcinoma and gallbladder cancer, a Phase 2 study is testing trifluridine/tipiracil with nanoliposomal irinotecan in patients whose disease did not respond to earlier gemcitabine treatment.[14] The study measures median progression-free survival, which is the time before the cancer grows or the patient dies from any cause.[14]
Another Phase 2 study in FGFR2b-positive advanced or metastatic stomach or gastroesophageal junction adenocarcinoma tests bemarituzumab with different standard treatments, including a cohort with Trifluridine/tipiracil, and it measures objective response rate in each group.[15]
Special patient groups and biomarker-based studies
Some trials focus on very specific patient groups, not just on the cancer type.[16] One Phase 2 study includes people with pMMR/MSS metastatic colorectal or gastroesophageal cancer who have known DPD deficiency, a condition defined in the trial by high plasma uracil, and it evaluates whether Trifluridine/tipiracil can replace fluoropyrimidine-based chemotherapy in first-line treatment.[16]
A Phase 2 study in metastatic colorectal cancer without active liver metastases looks at Fruquintinib plus Tislelizumab, and Trifluridine appears in the intervention list as part of the study design.[6] Another study in metastatic colorectal cancer with positive ctDNA after surgery tests whether post-operative treatment with Trifluridine/tipiracil plus bevacizumab can improve ctDNA clearance compared with observation or other adjuvant strategies.[17]
There is also a suspended Phase 2 study in stage III and high-risk stage II resected colon cancer that uses ctDNA testing to guide post-operative treatment, and Trifluridine is one of the study medicines listed for the treatment arms.[17] In another study, Trifluridine/tipiracil is used after pembrolizumab plus a dendritic cell vaccine in refractory pMMR/MSS metastatic colorectal cancer, with the main goal of measuring overall response rate.[18]
Main study endpoints
The studies use several common endpoints, which are the main results researchers want to measure.[1][2] Overall survival means how long patients live after starting the study treatment, and progression-free survival means how long the cancer does not get worse.[5][12]
Other important endpoints include objective response rate, time to recurrence, disease control rate, ctDNA clearance, and the rate of severe neutropenia.[4][17] Some trials also measure safety through adverse events, laboratory changes, vital signs, and ECG findings.[19]
In many studies, the tumor response is checked with RECIST 1.1, a standard scan-based system that tells researchers whether the cancer has shrunk, stayed stable, or grown.[10][8] This makes the results easier to compare across different trials.
Trial phases and study design
Most Trifluridine trials in the source data are Phase 2 or Phase 3 studies.[1][5] Phase 2 studies usually look more closely at early signs of benefit and safety, while Phase 3 studies compare treatments in larger groups and are often designed to confirm whether one option is better than another.[7][13]
One study is Phase 1/2 and focuses on dose escalation and dose expansion, which means researchers first check safety and then look for early signs of activity in selected cancer groups.[19] Enrollment sizes vary widely, from small studies with fewer than 40 patients to large Phase 3 trials with several hundred participants.[14][7]
Across the trial list, Trifluridine is being studied in adults with advanced cancer, often after earlier treatment has failed or when standard treatment options are limited.[4][12] Some studies also narrow the group by tumor markers, such as RAS/BRAF status, HER2 status, FGFR2b positivity, CLDN18.2 expression, PD-L1 score, MSS/pMMR status, or ctDNA positivity.[1][15][7]
