Trial results for a Phase 2 study (NCT04907539) investigating RXC004 as monotherapy and in combination with nivolumab for metastatic colorectal cancer were posted on ClinicalTrials.gov on 2025-04-16. The combination therapy achieved a median progression-free survival (PFS) of 3.9 months, compared to 2.0 months for RXC004 monotherapy.
Background
The study investigated RXC004 as monotherapy and in combination with nivolumab in patients with Ring finger protein 43 (RNF43) or R-spondin (RSPO) aberrated, metastatic, microsatellite stable (MSS), colorectal cancer (CRC) who had progressed following current standard of care treatment.
Trial design
The study (NCT04907539) was a Phase 2, open-label, multicenter, multi-arm study that enrolled 25 participants. It evaluated RXC004 as monotherapy and in combination with nivolumab in patients with Ring finger protein 43 (RNF43) or R-spondin (RSPO) aberrated, metastatic, microsatellite stable (MSS), colorectal cancer (CRC) who had progressed following standard of care. The study included two main arms: Arm A for RXC004 monotherapy and Arm B for RXC004 in combination with nivolumab.
Key results
Key results from the study included the following:
- For Disease Control Rate (DCR) using RECIST 1.1:
- Arm A (RXC004 Monotherapy) showed a DCR of 18.2%.
- Arm B (RXC004+Nivolumab Combination Therapy) showed a DCR of 57.1%.
- For Objective Response Rate (ORR) using RECIST 1.1:
- Arm A (RXC004 Monotherapy) showed an ORR of 0%.
- Arm B (RXC004+Nivolumab Combination Therapy) showed an ORR of 14.3%.
- For Best Percentage Change in Tumor Size:
- The median change in Arm A (RXC004 Monotherapy) was 9.34%.
- The median change in Arm B (RXC004+Nivolumab Combination Therapy) was 0.00%.
- For Progression Free Survival (PFS):
- The median PFS in Arm A (RXC004 Monotherapy) was 2.0 months.
- The median PFS in Arm B (RXC004+Nivolumab Combination Therapy) was 3.9 months.
- For Overall Survival (OS):
- The median OS in Arm A (RXC004 Monotherapy) was 4.8 months.
- The median OS in Arm B (RXC004+Nivolumab Combination Therapy) was not available.
- For Maximum Observed Plasma Concentration (Cmax):
- The geometric mean Cmax in Arm A (RXC004 Monotherapy) was 65.2 ng/mL (Geometric Coefficient of Variation: 62.0).
- The geometric mean Cmax in Arm B (RXC004+Nivolumab Combination Therapy) was 56.5 ng/mL (Geometric Coefficient of Variation: 56.4).
What this means
The results indicate that the combination of RXC004 with nivolumab demonstrated improved efficacy outcomes compared to RXC004 monotherapy in patients with RNF43 or RSPO aberrated, metastatic, microsatellite stable colorectal cancer. The higher disease control rate and objective response rate, along with a longer median progression-free survival and a median best percentage change in tumor size of 0.00%, suggest a potential clinical benefit for the combination regimen in this difficult-to-treat patient population.
Source
The information regarding these trial results was obtained from ClinicalTrials.gov, a public database of clinical studies. The results for study NCT04907539, titled 'A Study to Assess Efficacy of RXC004 +/- Nivolumab in Ring Finger Protein 43 (RNF43) or R-spondin (RSPO) Aberrated, Metastatic, Microsatellite Stable, Colorectal Cancer After Progression on Standard of Care (SOC),' were posted on 2025-04-16 on clinicaltrials.gov.