NALIRIFOX plus targeted therapy versus FOLFOX plus targeted therapy for first-line metastatic colorectal cancer

NALIRIFOX Plus Targeted Therapy Versus FOLFOX Plus Targeted Therapy as First-line Treatment for Metastatic Colorectal Cancer: a Multicentre, Open-label, Randomised Trial

Phase 3 Interventional Shanghai Zhongshan Hospital · NCT07309289

This study tests whether NALIRIFOX combined with a targeted drug works better and is safe compared with FOLFOX plus targeted therapy as the first treatment for adults with inoperable metastatic colorectal cancer.

Quick facts

PhasePhase 3
Study typeInterventional
Enrollment144 (estimated)
Ages18 Years and up
SexAll
SponsorShanghai Zhongshan Hospital Academic / other
Locations1 site (Shanghai)
Trial IDNCT07309289 on ClinicalTrials.gov

What this trial studies

This is a multicenter, open-label, randomized Phase 3 trial comparing NALIRIFOX plus targeted therapy to FOLFOX plus targeted therapy as first-line treatment for metastatic colorectal adenocarcinoma. Eligible adults have histologically confirmed unresectable metastatic disease, at least one measurable lesion by RECIST v1.1, ECOG 0-1, and adequate organ and bone marrow function. Patients who received prior neoadjuvant or adjuvant therapy are eligible only if progression occurred at least 12 months after last treatment, and those with MSI-H/dMMR deemed suitable for immunotherapy are excluded. The study focuses on safety and efficacy with scheduled radiographic assessments and treatment delivered in an open-label fashion.

Who should consider this trial

Good fit: Adults (≥18) with histologically confirmed, unresectable metastatic colorectal adenocarcinoma, no prior systemic therapy for metastatic disease, ECOG 0-1, measurable disease, and adequate organ function are ideal candidates.

Not a fit: Patients with MSI-H/dMMR who are suitable for immune checkpoint inhibitors, those allergic to the investigational agents, or those with recent progression within 12 months of adjuvant therapy are unlikely to benefit from enrollment.

Why it matters

Potential benefit: If successful, this regimen could improve response or disease control compared with current FOLFOX-based first-line therapy and offer an alternative option for patients.

How similar studies have performed: FOLFOX plus targeted therapy is an established first-line approach, while nal-IRI (liposomal irinotecan) combinations have shown promise in earlier-phase studies but are less established as first-line options.

Eligibility criteria

Show full inclusion / exclusion criteria
Inclusion Criteria:

* ≥18 years old
* Histopathologically confirmed patient with an inoperable metastatic colorectal adenocarcinoma
* The unresectable stage of metastatic disease has not received any systemic antitumor therapy
* For subjects previously receiving neoadjuvant or adjuvant therapy, the date of first discovery of disease progression must be at least 12 months removed from the date of last administration of neoadjuvant or adjuvant therapy
* The presence of at least 1 measurable lesion that can be evaluated according to the RECIST v1.1 criteria
* ECOG 0\~1
* Normal bone marrow and organ function
* Understand the situation of this study, patients and/or legal representatives voluntarily agree to participate in this study and sign informed consent form

Exclusion Criteria:

* Patients with known MSI-H or dMMR who were evaluated by investigators as suitable for treatment with immune checkpoint inhibitors.
* Patients allergic to the investigational drug and its excipients
* Underweight (body mass index \[BMI\]\<18.5 kg/m\^2
* Known or suspected central nervous system metastasis
* Received irinotecan before enrollment
* Had undergone surgery and other oncologic treatments within the first 4 weeks of enrollment
* Previous treatment-related toxicity didn't return to NCI-CTCAE v5.0 class I or below.
* The use of CYP3A, CYP2C8, and UGT1A1 inhibitors or inducers couldn't be discontinued or were not discontinued within 2 weeks prior to enrollment
* Serious gastrointestinal disorders
* Interstitial lung disease
* Tendency of arterial embolism and massive bleeding within 6 months before enrollment (except surgical bleeding)
* Patients with fluid accumulation that couldn't reach a stable state and small amount of pleural effusion or ascites on imaging without clinical symptoms could be enrolled
* Intestinal obstruction, or a risk of intestinal obstruction in the short term
* Gastrointestinal perforation, intraperitoneal abscess, and fistula
* Any serious or uncontrolled systemic disease, including uncontrolled high blood pressure, heart disease, active bleeding, active viral infection, etc
* Have had other malignancies within the past 5 years or currently, except cured cervical carcinoma in situ, uterine carcinoma in situ, and non-melanoma skin cancer
* Patients of childbearing age who refuse to take contraceptives, women who are pregnant or breastfeeding
* The researchers didn't consider it appropriate to participate in this study

Where this trial is running

Shanghai

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
Conditions Metastatic Colorectal Cancer
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.