Study of denikitug alone or in drug combination in adults with advanced microsatellite stable colorectal cancer

2 1 1 1

What is this study about?

The study examines adults with advanced microsatellite stable colorectal cancer, a type of tumor in the colon or rectum that lacks a specific genetic instability. The experimental medicine being tested is denikitug, which is given by intravenous infusion. It will be evaluated alone, together with nivolumab (an intravenous drug that helps the immune system attack cancer), or combined with an oral tablet containing trifluridine and tipiracil plus an intravenous infusion of bevacizumab (a drug that blocks blood‑vessel growth to tumors).

The purpose is to determine how well these treatments shrink or control the tumors, using the objective response rate measured by RECIST criteria, which are standard rules doctors use to judge changes in tumor size on scans. Participants are randomly assigned to one of the treatment groups, receive the assigned medicines in repeating cycles of a few weeks, and attend regular clinic visits for safety checks, blood tests, and imaging scans.

Safety is monitored throughout the study, with any side effects recorded and graded, and blood samples taken to measure drug levels. The study continues until a set number of participants have completed treatment or the disease progresses, and follow‑up visits occur after the last dose to assess long‑term outcomes.

1 enrollment and baseline assessments

after joining the study, baseline medical information is recorded, including a physical examination, laboratory tests, and imaging studies to document the current status of the cancer.

the participant provides written informed consent confirming understanding of the study procedures.

2 randomization to treatment group

the participant is assigned by the study system to one of three possible groups:

denikitug monotherapy,

denikitug combined with nivolumab,

or denikitug combined with trifluridine‑tipiracil and bevacizumab.

3 initial treatment administration

if assigned to denikitug monotherapy, a single intravenous infusion of denikitug 30 mg is given.

if assigned to the combination with nivolumab, an intravenous infusion of denikitug 30 mg is given together with an infusion of nivolumab 480 mg.

if assigned to the combination with chemotherapy, an intravenous infusion of denikitug 30 mg is given together with an infusion of bevacizumab 5 mg per kilogram of body weight, and the participant takes oral tablets of trifluridine‑tipiracil at a dose of 70 mg per square meter of body‑surface area.

4 repeated treatment cycles

the same set of medications is administered in each subsequent cycle according to the schedule defined in the study protocol.

intravenous infusions are performed in the clinic, and oral tablets are taken at home as directed.

the participant attends regular clinic visits for the administration of the infusions and for collection of safety information.

5 monitoring and assessments

at defined intervals, imaging studies are performed to evaluate tumor response according to standard criteria (recist version 1.1).

laboratory tests are repeated to monitor organ function and to detect any treatment‑emergent adverse events.

the participant reports any new symptoms or side effects to the study staff during each visit.

6 treatment continuation or discontinuation

treatment continues until disease progression is documented, unacceptable toxicity occurs, or the predefined end of the study period is reached.

if the study ends while the participant is still receiving therapy, the participant stops study medication and receives standard follow‑up care as determined by the treating physician.

Who Can Join the Study?

Have a confirmed diagnosis of advanced colorectal cancer that cannot be removed by surgery, has come back, or has spread, and it must be the MSS (microsatellite stable) type or have pMMR (proficient mismatch repair), which are determined by special lab tests called PCR (polymerase chain reaction) or IHC (immunohistochemistry).
The cancer must be an adenocarcinoma (the most common type of colon cancer) and not cancer of the appendix.
Have received no more than two previous lines of systemic therapy (treatments that affect the whole body) for advanced disease, and those treatments must have included standard chemotherapy drugs such as fluoropyrimidine, oxaliplatin, or irinotecan, possibly combined with targeted medicines like anti‑VEGF or anti‑EGFR agents when appropriate.
Show documented progressive disease (cancer getting worse) on a recent CT (computed tomography) scan or MRI (magnetic resonance imaging) using the standard measurement rules called RECIST (Response Evaluation Criteria in Solid Tumors).
Have an ECOG performance status score of 0 or 1, meaning they are fully active or able to do light work but not bedridden.
Be an adult (generally age 18 or older) of any gender.
Have adequate blood counts: ANC (absolute neutrophil count) ≥ 1.5 × 10⁹/L, platelets ≥ 100 × 10⁹/L, hemoglobin ≥ 9 g/dL, and not need a blood transfusion or growth‑factor medication in the past two weeks.
Have adequate liver function: total bilirubin ≤ 1.5 × the upper normal limit (or ≤ 3 × if liver metastases are present) and liver enzymes AST and ALT ≤ 2.5 × normal (or ≤ 5 × if liver metastases are present).
Have adequate kidney function: creatinine clearance ≥ 50 mL/min and urine protein low (≤ 1+ on a dipstick, or < 1000 mg in a 24‑hour collection if higher).
Have acceptable blood‑clotting numbers: INR or PT ≤ 1.5 × normal (unless taking anticoagulants) and aPTT ≤ 1.5 × normal (unless taking anticoagulants).

Who Cannot Join the Study?

Having recent serious heart or blood‑vessel problems, such as a heart attack (myocardial infarction), stroke, unstable chest pain (angina), blood clots, dangerous irregular heartbeats (like ventricular tachycardia or ventricular fibrillation), moderate to severe heart failure, or a weak heart pump (ejection fraction < 40%).
Having an immune‑system disease that needed strong whole‑body medicines (such as disease‑modifying drugs, steroids, or immunosuppressive drugs) within the past two years, or a history of gut inflammation conditions like non‑infectious enteritis/colitis, inflammatory bowel disease (Crohn’s disease or ulcerative colitis), or celiac disease.
Having a history of lung inflammation that is not caused by infection (called pneumonitis or interstitial lung disease), or currently having this condition, especially if it required steroid treatment.
Having recent serious gastrointestinal problems, such as a hole in the gut (GI perforation), a permanent ileostomy, an abdominal abscess or fistula within the last six months, active or uncontrolled gut bleeding within the last four weeks, or any condition that greatly increases the risk of bleeding or perforation (for example, untreated varices, tumor erosion, or recent gut surgery).
Having previously been treated with specific cancer drugs such as trifluridine‑tipiracil, regorafenib, fruquitinib, or any immunotherapy that targets the immune system (including PD‑1/PD‑L1 inhibitors, CTLA‑4 inhibitors, T‑reg modifying agents, or other checkpoint inhibitors), or having received any anticancer biologic, chemotherapy, targeted therapy, or radiation within the two weeks before the study and not fully recovered from side effects.
Having received an organ or stem‑cell transplant from another person (allogeneic transplantation), except for a corneal (eye) transplant that does not require ongoing immune‑suppressing medication.

Where you can join this trial?

Verified and Recommended Sites

No sites found in this category

Verified Sites

Site Name	City	Country
Centre Hospitalier Universitaire De Lille	Lille	France
Institut Gustave Roussy	Villejuif	France
Oncopole Claudius Regaud	Toulouse	France
Centr Georges Francois Leclerc	Dijon	France
Fondazione Policlinico Universitario Agostino Gemelli IRCCS	Rome	Italy
Hospital Universitario Hm Sanchinarro	Madrid	Spain
Azienda Ospedaliera Universitaria Universita’ Degli Studi Della Campania Luigi Vanvitelli	Naples	Italy

Other Sites

Site Name	City	Country
Istituto Oncologico Veneto	Padua	Italy
Istituto Europeo Di Oncologia S.r.l.	Milan	Italy
Hospital General Universitario Gregorio Maranon	Madrid	Spain
Hopital Beaujon	Clichy	France
Hospital Universitario 12 De Octubre	Madrid	Spain
Fondazione I.R.C.C.S. Istituto Neurologico Besta	Milan	Italy
Azienda Ospedaliero Universitaria Pisana	Pisa	Italy
Inuhcibp Rvyirsit Du Culdvs Dj Mdxvuqrktpz	Montpellier	France
Itnxpkmw Pvewyaowmjhxgle Cpucee Cdzbdt	Marseille	France
Hmuydqrx Vtsu dxpxqsak	Barcelona	Spain
Ivqcndjy Cbgbfu Dwweaszdizilwvync	L'hospitalet De Llobregat	Spain

Trial status

Country	Status	Recruitment Start
France	Not yet recruiting	01.06.2026
Italy	Not yet recruiting	01.06.2026
Spain	Not yet recruiting	01.06.2026

Trial locations

Investigated drugs:

Denikitug is a laboratory‑made antibody designed to attach to a protein called CCR8 on certain immune cells. By binding to CCR8, it may help the immune system recognize and fight colorectal cancer cells. In this study, denikitug is tested by itself (monotherapy) and also together with other medicines to see how well it works.

Nivolumab is an immunotherapy that blocks a protein called PD‑1 on immune cells. This blockage can release the brakes on the immune system, allowing it to attack cancer more effectively. In the trial, nivolumab is combined with denikitug to explore whether the two drugs together improve the response against advanced colorectal cancer.

Trifluridine‑tipiracil (often known by the brand name Lonsurf) is a combination of two chemotherapy agents taken by mouth. Trifluridine interferes with the DNA of cancer cells, while tipiracil helps keep trifluridine active longer in the body. This oral therapy is used in the study together with denikitug and bevacizumab to assess a multi‑drug approach.

Bevacizumab is a medication that stops new blood vessels from growing to feed tumors. By blocking a protein called VEGF, it can slow tumor growth and make other treatments work better. In the trial, bevacizumab is given along with denikitug and trifluridine‑tipiracil to test whether this combination can increase tumor shrinkage in patients with advanced colorectal cancer.

Investigated diseases:

Colorectal cancer

Advanced microsatellite stable colorectal cancer – This is a type of cancer that begins in the lining of the colon or rectum and does not show the DNA changes called microsatellite instability. The tumor starts as a small growth and can enlarge to involve deeper layers of the bowel wall. Over time it may spread to nearby lymph nodes and can travel through the bloodstream to other parts of the body such as the liver or lungs. The disease usually advances step by step, moving from a localized area to more widespread involvement.

Trial ID:

2025-523984-39-00

Protocol code:

GS-US-741-7756

Trial Phase:

Therapeutic exploratory (Phase II)

Other Trials to Consider

#1 Clinical Trials Search in Europe

Study of denikitug alone or in drug combination in adults with advanced microsatellite stable colorectal cancer

What is this study about?

Who Can Join the Study?

Who Cannot Join the Study?