Phase 2
N=25
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)
Colorectal Cancer
Bottom Line
View on ClinicalTrials.gov: NCT04907539 ↗Enrolled (actual)
25
Serious AEs
32.0%
Results posted
Apr 2025
Primary outcome: Primary: RXC004 Monotherapy (Arm A): Disease Control Rate (DCR) Using Each Patient's Best Overall Response (BOR) According to Response Evaluation Criteria in Solid Tumours, Version 1.1 (RECIST 1.1) — 18.2 Percentage of patients
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- RXC004 (Drug); Nivolumab (Biological); Denosumab (Biological)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Redx Pharma Ltd
- Primary completion
- Apr 2024
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY RXC004 Monotherapy (Arm A): Disease Control Rate (DCR) Using Each Patient's Best Overall Response (BOR) According to Response Evaluation Criteria in Solid Tumours, Version 1.1 (RECIST 1.1) |
18.2 | — |
| PRIMARY RXC004+Nivolumab Combination Therapy (Arm B): Objective Response Rate (ORR) Using Each Patient's BOR According to RECIST 1.1 |
14.3 | — |
| SECONDARY Best Percentage Change in Tumor Size |
9.34; 0.00 | — |
| SECONDARY Progression Free Survival (PFS) |
2.0; 3.9 | — |
| SECONDARY Duration of Response (DOR) |
— | — |
| SECONDARY RXC004 Monotherapy (Arm A): Objective Response Rate (ORR) Using Investigator Assessments According to RECIST 1.1 |
— | — |
| SECONDARY RXC004 + Nivolumab Combination Therapy (Arm B): Disease Control Rate Using Investigator Assessments According to RECIST 1.1 |
57.1 | — |
| SECONDARY Overall Survival (OS) |
4.8; NA | — |
| SECONDARY Maximum Observed Plasma Concentration (Cmax) |
65.2; 56.5; 80.0; 79.4 | — |
| SECONDARY Time to Maximum Plasma Concentration (Tmax) |
2.07; 1.95; 1.35; 1.98 | — |
| SECONDARY Minimum Observed Concentration Across the Dosing Interval (Cmin) |
12.8; 17.2 | — |
| SECONDARY Terminal Rate Constant (λz) |
0.0769; 0.0540 | — |
| SECONDARY Terminal Half-life (t½) |
9.02; 12.2 | — |
| SECONDARY Area Under the Plasma Concentration-time Curve From Zero to Infinity (AUC0-∞) |
733; 749 | — |
| SECONDARY Total Plasma Clearance After Oral Administration (CL/F) |
2730; 2000 | — |
| SECONDARY Apparent Volume of Distribution After Oral Administration (Vz/F) |
32300; 35800 | — |
| SECONDARY Number of Patients With Adverse Events (AEs) |
17; 8; 14; 8; 1; 5 | — |
Summary
This is a Phase II, open label, multicentre, multi-arm, study to evaluate the preliminary efficacy and safety of RXC004 as monotherapy and in combination with nivolumab in patients with Ring finger protein 43 (RNF43) or R-spondin (RSPO) aberrated, microsatellite stable (MSS), colorectal cancer (CRC), that have progressed following current standard of care treatment.
Eligibility Criteria
Inclusion Criteria
- Histological documentation of metastatic (Stage IV) Colorectal cancer (CRC) and
- Documented tumour tissue aberration in RNF43 and/or RSPO
- Documented confirmation of microsatellite stable (MSS) status
- Patients must have had documented radiological progression following a minimum of 1 prior SOC treatment regimen for metastatic disease
- Eastern Cooperative Oncology Group performance status 0 or 1
- At least one lesion that is measurable by RECIST 1.1 at baseline
- Patients must have at least one lesion suitable for biopsy at screening and be willing to provide mandatory tumour biopsy samples
- Patients with adequate organ functions
- Female patients of childbearing potential must have a negative pregnancy test prior to start of dosing
- Female patients of childbearing potential and male patients with female partners of childbearing potential must agree to use a highly effective method of contraception during the study and for at least 5 months after the last dose of study drug.
For patients on RXC004 monotherapy treatment (Arm A) the following inclusion criteria will also apply to enter the RXC004 + nivolumab treatment phase:
- Patients must have had documented RECIST1.1 defined radiological progression on RXC004 monotherapy treatment on the first scheduled scan (week 8 +/- 1 week)
- Patients must receive Cycle 1 Day 1 of combination study treatment within 28 days of the first scheduled scan (week 8 +/- 1 week).
Exclusion Criteria
- Prior therapy with a compound of the same mechanism of action as RXC004
- Patients at higher risk of bone fractures
- Any known uncontrolled inter-current illness or persistent clinically significant toxicity related to prior anti-cancer treatment
- Patients who have any history of an active (requiring treatment) other malignancy within 2 years of study entry
- Patients with known or suspected brain metastases
- Use of anti-neoplastic agents, immunosuppressants and other investigational drugs
- Patients with a known hypersensitivity to any RXC004 excipients
- Patients with a contra-indication for denosumab treatment
- Patients who are pregnant or breast-feeding
- Use of any live or live-attenuated vaccines against infectious diseases (e.g., influenza nasal spray, varicella) within 4 weeks (28 days) of initiation of study treatment
- Patients with a mean resting corrected QTcF >470 ms, obtained from triplicate electrocardiograms performed at screening
For patients on RXC004 + nivolumab combination treatment (Arm B or Arm A RXC004 + nivolumab treatment phase):
- Patients with any contraindication to the use of nivolumab
- Patients with active or prior documented autoimmune or inflammatory disorders within the past 5 years
- Patients with active infections, including tuberculosis, hepatitis B, hepatitis C or human immunodeficiency virus
- Patients with a history of allogeneic organ transplant or active primary immunodeficiency
- Patients with a known hypersensitivity to nivolumab or any of the excipients of the product
Data sourced from ClinicalTrials.gov (NCT04907539). 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.