Phase 2
Completed N=111
A Safety, Pharmacokinetic and Efficacy Study of NUC-3373 in Combination With Standard Agents Used in Colorectal Cancer Treatment
Colorectal Cancer · Colorectal Tumors · Neoplasms, Colorectal
Source: ClinicalTrials.gov NCT03428958 ↗
Enrolled (actual)
111
Serious AEs
39.6%
Results posted
Apr 2025
Primary outcomePrimary: Percentage Change From Baseline in Tumour Size — 8.3; 2.9; 3.2; 2.3 Percent change
Summary
This is a three-part study of NUC-3373 administered by intravenous (IV) infusion across two administration schedules, either as monotherapy or as part of various combinations with agents commonly used to treat CRC (leucovorin, oxaliplatin, irinotecan, bevacizumab, cetuximab and panitumumab). The primary objective is to identify a recommended dose and schedule for NUC-3373 when combined with these agents.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage Change From Baseline in Tumour Size |
8.3; 2.9; 3.2; 2.3; 7.9; 2.8 | — |
| PRIMARY Disease Control Rate (DCR) |
0; 42.9; 62.5; 50; 46.7; 42.9 | — |
| PRIMARY Duration of Stable Disease (DoSD) |
1.9; 2.6; 1.9; 3.7; 3.2; 2.3 | — |
| PRIMARY Progression Free Survival (PFS) |
1.7; 2.3; 2.9; 1.8; 2.5; 3.6 | — |
| PRIMARY Overall Survival (OS) |
1.9; 3.0; 3.6; 3.6; 3.4; 3.2 | — |
| PRIMARY Best Overall Response |
0; 0; 0; 0; 0; 0 | — |
Eligibility Criteria
Inclusion Criteria
All patients
- Provision of written informed consent
- Have histological confirmation of CRC with evidence of locally advanced/unresectable or metastatic disease
- Age ≥18 years
- Life expectancy of ≥12 weeks
- ECOG Performance status 0 or 1
- Measurable disease as defined by RECIST v1.1
- Known RAS and BRAF status. Patients with wild-type KRAS tumours who are to be enrolled to a cohort that does not contain an EGFR pathway inhibitor (Arms 2a, 2b, 2c, 2d, 3a, 3b, 3c, 3d and 3e) must have received prior treatment with an EGFR inhibitor, unless this was not standard of care according to relevant region-specific treatment recommendations. Patients with BRAF V600E mutant tumours should have received prior treatment with encorafenib in combination with an EGFR inhibitor, unless this was not standard of care according to relevant region-specific treatment recommendations
- Adequate bone marrow function as defined by: ANC ≥1.5×10^9/L, platelet count ≥100×10^9/L (with no evidence of bleeding), and haemoglobin ≥9 g/dL
- Adequate liver function as defined by serum total bilirubin ≤1.5×ULN, AST and ALT ≤2.5×ULN (or ≤5×ULN if liver metastases present)
- Adequate renal function assessed as serum creatinine 3rd-line patients
- Received at least two prior lines of therapy for locally advanced or metastatic CRC, including one fluoropyrimidine plus oxaliplatin and one fluoropyrimidine plus irinotecan containing regimen. Previous treatment with SoC regimens in combination with molecular targeted therapies is permitted and patients who received FOLFOXIRI-based regimens in 1st-/2nd-line settings may be included.
- Patients due to receive NUFOX should be suitable for re-challenge with an oxaliplatin-based regimen
- Patients due to receive NUFIRI should be suitable for re-challenge with an irinotecan-based therapy
2nd-/3rd-line patients
- Received at least one but no more than two prior lines of fluoropyrimidine-containing therapy in combination with oxaliplatin and/or irinotecan for locally advanced or metastatic CRC. Previous treatment with SoC regimens in combination with molecular targeted therapies is permitted and patients who received FOLFOXIRI-based regimens in 1st-/2nd-line settings may be included. 3rd-line patients enrolled to Arms 2c and 2d must have received prior bevacizumab treatment, unless ineligible or unless bevacizumab was not standard of care according to relevant region-specific treatment recommendations
- Patients in Part 2 due to receive NUFOX should be suitable for re-challenge with an oxaliplatin-based regimen
- Patients in Part 2 due to receive NUFIRI should be suitable for re-challenge with an irinotecan-based regimen
Combination chemotherapy ineligible patients
- May have received one prior fluoropyrimidine-containing regimen for locally advanced or metastatic CRC
- Ineligible to receive combination therapy for locally advanced or metastatic CRC
- Creatinine clearance >30mL/min
Rapid progressors
- Received no more than two prior lines of fluoropyrimidine-containing therapy in combination with oxaliplatin and/or irinotecan for locally advanced or metastatic CRC. Previous treatment with SoC regimens in combination with molecular targeted therapies is permitted and patients who received FOLFOXIRI-based regimens in 1st-/2nd-line settings may be included.
- Have had tumour progression ≤3 months of starting the last fluoropyrimidine-containing regimen
- Patients due to receive NUFOX should be suitable for re-challenge with an oxaliplatin-based regimen
- Patients due to receive NUFIRI should be suitable for re-challenge with an irinotecan-based regimen
2nd-line patients
- Received one prior line of fluoropyrimidine-containing therapy in combination with oxaliplatin and/or irinotecan for locally advanced or metastatic CRC. Previous treatment with SoC regimens in combination with molecular targeted therapies is permitted and patients who received triplet chemotherapy based
Data sourced from ClinicalTrials.gov (NCT03428958). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.