New Combination Therapy with Fruquintinib and Tislelizumab for Advanced Colorectal Cancer Without Liver Metastases

Colorectal cancer (bowel cancer) is one of the most common cancers worldwide. It affects the large intestine (colon) or the rectum and, in advanced stages, can form metastases (distant spread of cancer cells) in other organs—most commonly in the liver or lungs. Treatment depends on the stage of the disease and typically involves a combination of surgery, chemotherapy, and, if necessary, targeted therapies or radiation therapy. A subtype that is particularly difficult to treat is the so-called MSS/pMMR colorectal carcinoma (Microsatellite Stable / proficient Mismatch Repair). These tumors do not exhibit specific genetic alterations, which means they rarely respond to immunotherapy. Patients with MSS/pMMR tumors without active liver metastases have a particular need for treatment, as standard therapies often do not provide long-term benefits. Studies such as QUINTIS therefore aim to specifically test innovative combination therapies in this patient group. To this end, two different drug combinations are being compared. The first combination consists of fruquintinib and tislelizumab. Fruquintinib is a so-called tyrosine kinase inhibitor (TKI) that blocks certain proteins (tyrosine kinases) that promote the growth and proliferation of cancer cells. The drug is already approved in the U.S. and Europe for metastatic colorectal cancer. Tislelizumab is a so-called PD-1 inhibitor that activates the immune system and slows tumor growth. To date, the drug has only been approved for the treatment of other types of cancer.

The second combination corresponds to an established standard of care and consists of trifluridine/tipiracil, a specific chemotherapy, and bevacizumab, an antibody that, similar to fruquintinib, slows tumor growth by inhibiting the blood supply. The goal of this Phase 2 study is to investigate the safety and efficacy of this new combination therapy of fruquintinib and tislelizumab and to compare it with the current standard of care. To this end, patients will be randomly assigned to two treatment groups. The randomization takes into account whether patients have already received therapy to inhibit the tumor’s blood supply, whether certain genetic mutations (BRAF or RAS) are present, and whether they have had liver metastases in the past (never detected vs. treated in the past). In Group A (new combination therapy), patients receive fruquintinib as a tablet on days 1–21 of a 28-day cycle. In addition, they receive an infusion of tislelizumab every six weeks. Group B (control group) receives trifluridine/tipiracil in tablet form. They also receive an infusion of bevacizumab every two weeks. Treatment will continue as long as it is effective and well-tolerated—for a maximum of 15 months. The study is open-label, meaning that all patients and the treating physicians know which medication they are receiving. The primary endpoint of the study is progression-free survival (PFS), i.e., the time until the disease progresses. Follow-up will continue for approximately 4 years after completion of treatment.

Eligible participants are patients aged 18 and older who have been diagnosed with metastatic colorectal cancer (MSS/pMMR status) and have no active liver metastases. The disease must no longer be treatable with curative surgery. Another requirement is that patients must have already received at least one prior treatment for the cancer, including chemotherapy with fluoropyrimidine, oxaliplatin, or irinotecan, as well as targeted therapies against VEGF, EGFR, or BRAF. If these therapies were not tolerated or could not be used for medical reasons, participation is still possible. In addition, certain genetic characteristics (RAS or BRAF status) of the tumor must be known. Patients whose previous liver metastases have been successfully treated and who currently show no signs of recurrent liver involvement may also participate.

Study Facts:

1. Disease: colorectal carcinoma (colon cancer)
2. Cancer characteristics: metastatic, previously treated, no active liver metastases, molecularly defined tumor type (MSS/pMMR), curative resection not possible, known RAS or BRAF status
3. What the study investigates: Comparison of the combination of immunotherapy and targeted therapy with current standard therapy (third- or fourth-line treatment)
4. Study objective: To prolong the time to disease progression (progression-free survival)
5. How long the study lasts: Treatment for up to 15 months, follow-up for up to 4.5 years
6. Study characteristics: Phase 2 study, two treatment arms, random assignment (but based on specific criteria), open-label