In short
Clinical trials are investigating Trifluridine in several cancer settings, especially colorectal and gastric cancers. These studies look at safety, effectiveness, and how Trifluridine works in different treatment plans and patient groups, including people with advanced, metastatic, or hard-to-treat disease.
Key points
- Clinical trials investigating Trifluridine are mostly focused on advanced and metastatic cancers, especially colorectal cancer. The studies also include gastric, gastroesophageal junction, esophageal, cholangiocarcinoma, gallbladder, and breast cancer. Most trials are Phase 2 or Phase 3, with one Phase 1/2 study, and many compare Trifluridine-based treatment with other cancer medicines or with standard care. The main goals are to measure survival, tumor response, time without disease growth, and safety. Several studies target special patient groups, such as people with biomarker-defined tumors, DPD deficiency, or disease that has returned after earlier treatment.
Clinical trials overview
These studies investigate Trifluridine mainly in cancer treatment plans for people with advanced, metastatic, or hard-to-treat disease. Most trials are in colorectal cancer, but there are also studies in gastric, gastroesophageal junction, oesophageal, cholangiocarcinoma, gallbladder, and breast cancer.
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. 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.
Colorectal cancer studies
Colorectal cancer is the main area of research for Trifluridine in the trial data. Several studies look at metastatic colorectal cancer, which means cancer that has spread beyond the colon or rectum.
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. 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.
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. 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.
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. 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. 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.
Other gastrointestinal cancer studies
Several trials study Trifluridine in cancers of the stomach and nearby organs. 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.
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. 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.
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. The study measures median progression-free survival, which is the time before the cancer grows or the patient dies from any cause.
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.
Special patient groups and biomarker-based studies
Some trials focus on very specific patient groups, not just on the cancer type. 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.
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. 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.
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. 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.
Main study endpoints
The studies use several common endpoints, which are the main results researchers want to measure. 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.
Other important endpoints include objective response rate, time to recurrence, disease control rate, ctDNA clearance, and the rate of severe neutropenia. Some trials also measure safety through adverse events, laboratory changes, vital signs, and ECG findings.
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. 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. 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.
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. Enrollment sizes vary widely, from small studies with fewer than 40 patients to large Phase 3 trials with several hundred participants.
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. 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.