New combo for colorectal cancer shows promise but trial halted early

NCT ID NCT05678257

Disease control Sponsor: NuCana plc Source: ClinicalTrials.gov ↗

First seen Jun 25, 2026 · Last updated Jun 26, 2026 · Updated 2 times

Summary

This phase 2 trial tested a new drug combination (NUFIRI-bev) against the standard treatment (FOLFIRI-bev) in 171 people with metastatic colorectal cancer that had already been treated. The goal was to see if the new combo could delay cancer growth better than the standard. However, the study was terminated early, so we have less information than planned.

What this could mean

Our plain-language read of the trial. This is informational only, not medical advice or a prediction.

Active substance: Fosifloxuridine Nafalbenamide (NUC-3373) plus leucovorin, irinotecan, and bevacizumab
What this could lead to: If successful, this could offer a new treatment option for people with metastatic colorectal cancer that has stopped responding to first-line therapy.
What could go wrong: The trial was terminated early, so results are limited. It is a phase 2 study, meaning it is still early-stage and may not lead to a proven treatment.

This is an AI summary of the original study and may miss details. Read our disclaimer.

Study facts

What this study's own registry entry says, in plain language.

Phase

Phase 2

Tests whether the treatment actually works, and watches for side effects, in a larger group.

Participants

180 people

The number who actually took part.

Started

Apr 2023

Finished

Aug 2024

Lead sponsor

Other sponsor

The registry's catch-all category, for sponsors it does not file as a company, a government agency, or a research network.

Who can take part

This study's own entry requirements. Only the study team can say for certain whether you qualify.

Ages

18 years and older

Sex

Anyone

Healthy volunteers

Not accepted

This study is not open to healthy volunteers. The entry requirements below say who it is open to.

Show the full entry requirements

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

Inclusion Criteria: 1. Provision of written informed consent. 2. Histological or cytological confirmation of colorectal adenocarcinoma (excluding appendiceal and anal canal cancers, as well as signet-ring cell carcinoma) that is unresectable and metastatic. 3. Measurable disease (as defined by RECIST v1.1). 4. Received ≥2 months of a first-line fluoropyrimidine and oxaliplatin-containing regimen for metastatic disease or relapsed within 6 months of completing a fluoropyrimidine and oxaliplatin-containing neoadjuvant/adjuvant therapy. Previous treatment with standard of care chemotherapy regimens in combination with molecular targeted therapies (e.g., VEGF and EGFR pathway inhibitors and immuno-oncology agents) is permitted. Previous treatment with maintenance therapy (e.g., capecitabine) is also allowed. Patients who started on a fluoropyrimidine and oxaliplatin-containing regimen in any setting but must discontinue the oxaliplatin due to.toxicity or allergy (and are now unable to receive oxaliplatin) are considered eligible regardless of the number of cycles of oxaliplatin they received. 5. Known RAS and BRAF status. Patients with wild-type RAS tumours must have received prior treatment with an EGFR inhibitor, unless this was not standard of care according to relevant region-specific treatment recommendations. 6. Known UGT1A1 status, or patient consents to UGT1A1 status testing if unknown. 7. Known DPD activity status, or patient consents to DPD status testing if unknown. See exclusion criterion 1. 8. Age ≥18 years. 9. Minimum life expectancy of ≥12 weeks. 10. Eastern Cooperative Oncology Group (ECOG) Performance status 0 or 1. 11. Adequate bone marrow function as defined by: absolute neutrophil count (ANC) ≥1.5 × 109/L, platelet count ≥100 × 109/L, and haemoglobin ≥9 g/dL. Patients with benign neutropenia may be discussed on a case-by-case basis with the medical monitor. 12. Adequate liver function, as defined by: serum total bilirubin ≤1.5 × ULN), AST and ALT ≤2.5 × ULN (or ≤5 × ULN if liver metastases are present). 13. Adequate renal function assessed as serum creatinine \<1.5 × ULN and glomerular filtration rate ≥50 mL/min (calculated by the Cockcroft-Gault method). 14. Serum albumin ≥3 g/dL. 15. Ability to comply with protocol requirements. 16. Female patients of child-bearing potential must have a negative serum pregnancy test within 7 days prior to the first study drug administration. This criterion does not apply to patients who have had a previous hysterectomy or bilateral oophorectomy. Male patients and female patients of child-bearing potential must agree to practice true abstinence (defined in Section 10.3.1) or to use two forms of contraception, one of which must be highly effective. These forms of contraception must be used from the time of signing consent, throughout the treatment period, and for 6 months following the last dose of any study medication. Oral or injectable contraceptive agents cannot be the sole method of contraception 17. Patients must have been advised to take measures to avoid or minimize exposure of the skin and eyes to UV light, including avoiding sunbathing and solarium use, for the duration of study participation and for a period of 4 weeks following the last dose of study medication Exclusion Criteria: 1. History of hypersensitivity or current contra-indications to 5-FU, FUDR, or capecitabine. 2. History of hypersensitivity or current contra-indication to any of the combination agents required for the study. 3. History of allergic reactions attributed to components of the NUC-3373 drug product formulation. 4. History of hypersensitivity to Chinese Hamster Ovary (CHO) cell products or other recombinant human or humanised antibodies. 5. History of or known central nervous system or leptomeningeal metastases. 6. Symptomatic ascites, ascites currently requiring drainage procedures or ascites requiring drainage over the prior 3 months. 7. Mutant BRAF V600E status. 8. MSI high or dMMR. 9. Prior treatment with irinotecan. 10. Chemotherapy, hormonal therapy, radiotherapy (other than a short cycle of palliative radiotherapy \[e.g., for bone pain\]\*), immunotherapy, biological agents, or exposure to another investigational agent within 21 days (or four times the half-life for molecular targeted agents, whichever is shorter) of first administration of study treatment: 11. Residual toxicities from prior chemotherapy or radiotherapy which have not regressed to Grade ≤1 severity (CTCAE v5.0), except for alopecia and residual Grade 2 neuropathy. 12. History of other malignancies, except adequately treated non-melanoma skin cancer, curatively treated in situ cancer of the cervix, surgically excised or potentially curatively treated ductal carcinoma in situ of the breast, or low-grade prostate cancer or patients after prostatectomy. Patients with previous invasive cancers are eligible if treatment was completed \>3 years prior to initiating the current study treatment, and the patient has had no evidence or recurrence since then. 13. Presence of an active bacterial or viral infection (including SARS-CoV-2, Herpes Zoster, Varicella Zoster or chickenpox), known Human Immunodeficiency Virus (HIV) positive or known active hepatitis B or C. 14. Presence of any uncontrolled concurrent serious illness, medical condition or other medical history, including laboratory results, which, in the Investigator's opinion, would be likely to interfere with the patient's ability to participate in the study or with the interpretation of the results (refer to protocol for further details). 15. Any condition that, in the judgment of the Investigator, may affect the patient's ability to provide informed consent and undergo study procedures. 16. Patients with a history of haemoptysis (1/2 teaspoon or more of red blood) within 6 months prior to enrolment. 17. Wound healing complications or surgery within 28 days of starting bevacizumab (wound healing must have been fully completed before starting bevacizumab). Investigators may allow patients to initiate treatment with the other study drugs (i.e., NUC-3373/5-FU, LV and irinotecan) on C1D1 but withhold bevacizumab for at least 15 days, but no longer than 28 days, to allow completion of wound healing in patients who would otherwise be eligible for the study, in line with standard local practice and after discussion with the Medical Monitor. Patients who have not received bevacizumab by C2D1 must be replaced. 18. Unhealed wound, active gastric or duodenal ulcer, or bone fracture. 19. Serious thromboembolic event in the 6 months before inclusion. 20. Patients with a history of haemorrhage within 6 months prior to enrolment. 21. Known inherited or acquired bleeding disorders. 22. Red blood cell (RBC) transfusion dependence, defined as requiring more than 2 units of packed RBC transfusions during the 4-week period prior to screening. 23. Uncontrolled hypertension. 24. Severe proteinuria or nephrotic syndrome. 25. Acute intestinal obstruction or sub-obstruction, history of inflammatory intestinal disease or extended resection of the small intestine. Presence of a colic prosthesis. 26. History of abdominal fistulas, trachea-oesophageal fistulas, any other Grade 4 gastrointestinal perforations, non-gastrointestinal fistulas, or intra-abdominal abscesses 6 months prior to screening. 27. Currently pregnant, lactating or breastfeeding. 28. Required concomitant use of brivudine, sorivudine and analogues. 29. Required concomitant use of St John's Wort. 30. Required concomitant use of drugs known to prolong QT/QTc interval. 31. Required concomitant use of strong CYP3A4 inducers or strong CYP3A4 inhibitors. The use of strong CYP3A4 inducers within 2 weeks of first receipt of study drug or the use of strong CYP3A4 inhibitors within 1 week of first receipt of study drug is also excluded.

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Conditions

The condition(s) this trial relates to.

colonic neoplasm colorectal adenocarcinoma colorectal cancer colorectal neoplasm neoplasm Neoplasm Metastasis

As listed by the trial registrant

The condition terms exactly as the trial's registrant entered them.

Colorectal adenocarcinoma Colorectal cancer Colorectal cancer metastatic Colorectal neoplasms Neoplasm, colorectal

Contacts and locations

Locations

Azienda Ospedaliera Regionale San Carlo

Potenza, 85100, Italy
Azienda Ospedaliera Universitaria - Università degli Studi della Campania Luigi Vanvitelli

Naples, Campania, 80131, Italy
Azienda Ospedaliero Universitaria Careggi

Florence, Tuscany, 50134, Italy
Azienda Ospedaliero Universitaria Ospedali Riuniti di Ancona

Ancona, 60126, Italy
Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda

Milan, 20162, Italy
Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, 48201, United States
Boston Medical Center

Boston, Massachusetts, 02118, United States
Cancer Center of Kansas

Wichita, Kansas, 67214, United States
Centre Georges-François Leclerc

Dijon, Bourgogne-Franche-Comté, 21079, France
Centre Hospitalier Régional et Universitaire de Besançon - Hôpital Jean-Minjoz

Besançon, Doubs, 25000, France
Centre Hospitalier Universitaire de Poitiers

Poitiers, Vienne, 86000, France
Centre Hospitalier UniversitaireNantes - Hôtel Dieu

Nantes, 44000, France
Charité Campus Virchow-Klinikum

Berlin, 13353, Germany
Complejo Hospitalario Universitario de Santiago (CHUS)

Santiago de Compostela, La Coruña, 15706, Spain
Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, Lombardy, 20133, Italy
Fred Hutchinson Cancer Center at Evergreen Health

Kirkland, Washington, 98034, United States
Georgetown University Medical Center

Washington D.C., District of Columbia, 20007, United States
Guy's and Saint Thomas' NHS Foundation Trust

London, Greater London, SE1 9RT, United Kingdom
Helen F. Graham Cancer Center

Newark, Delaware, 19713, United States
Hospital Duran i Reynals

Barcelona, 8908, Spain
Hospital General Universitario Gregorio Marañón

Madrid, 28007, Spain
Hospital Universitari Arnau de Vilanova

Lleida, 25198, Spain
Hospital Universitari Vall d'Hebrón

Barcelona, 8035, Spain
Hospital Universitario 12 de Octubre

Madrid, 28041, Spain
Hospital Universitario Fundación Alcorcón

Alcorcón, Madrid, 28922, Spain
Hospital Universitario Puerta de Hierro

Majadahonda, Madrid, 28222, Spain
Hospital Universitario Virgen de la Victoria

Málaga, 29010, Spain
Hospital Universitario Virgen del Rocío

Seville, 41013, Spain
Hospital de León

León, 24008, Spain
Hospital de la Santa Creu i Sant Pau

Barcelona, 08041, Spain
Hôpital Européen Georges-Pompidou

Paris, Île-de-France Region, 75015, France
Hôpital Européen Marseille

Marseille, Bouches-du-Rhône, 13003, France
Hôpital Foch

Suresnes, Île-de-France Region, 92150, France
Institut Bergonié

Bordeaux, Gironde, 33076, France
Institut Català d'Oncologia - ICO Badalona - Hospital Universitari Germans Trias i Pujol

Badalona, Barcelona, 08916, Spain
Istituto Oncologico Veneto - IRCCS

Padova, Veneto, 35128, Italy
Krankenhaus Nordwest

Frankfurt am Main, Hesse, 60488, Germany
MD Anderson Cancer Center Madrid

Madrid, 28033, Spain
Morristown Medical Center

Morristown, New Jersey, 07960, United States
Mount Vernon Cancer Centre - East and North Hertfordshire NHS Trust

Northwood, Middlesex, HA6 2RN, United Kingdom
München Klinik Neuperlach

München, Bavaria, 81737, Germany
NHS Greater Glasgow and Clyde

Glasgow, G51 4TF, United Kingdom
Northwest Cancer Specialists, P.C. dba Compass Oncology - Vancouver Cancer Center

Vancouver, Washington, 98684, United States
Norton Cancer Institute

Louisville, Kentucky, 40202, United States
Ospedale Santa Maria delle Croci di Ravenna

Faenza, Ravenna, 48121, Italy
Queen's Hospital

Romford, Essex, RM7 OAG, United Kingdom
Royal Free London NHS Foundation Trust

London, Greater London, NW3 2QG, United Kingdom
Strasbourg Oncology Liberale - Clinique Sainte-Anne

Strasbourg, Alsace, 67000, France
Texas Oncology - Baylor Charles A. Sammons Cancer Center

Dallas, Texas, 75246, United States
The Christ Hospital Cancer Center

Cincinnati, Ohio, 45219, United States
The Christie NHS Foundation Trust

Manchester, Lancashire, M20 4BX, United Kingdom
USOR - Texas Oncology Northeast Texas

Tyler, Texas, 75702, United States
University College London Hospitals NHS Foundation Trust

London, Greater London, NW1 2PG, United Kingdom
University of Florida Health Medical Oncology - Davis Cancer Pavilion

Gainesville, Florida, 32610, United States
University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242, United States
University of Massachusetts Worcester

Worcester, Massachusetts, 01655, United States
University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States
Universitätsklinik Ulm - Oberen Eselsberg

Ulm, Tübingen, 89081, Germany
Velindre University NHS Trust

Cardiff, CF14 2TL, United Kingdom

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