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)

NCT04907539 | Completed Phase 2 Results FDA Drug

• 1 other identifier: RXC004/0002
• Study Type: interventional
• Target: 25
• Locations: 4 countries
• Sites: 22

Brief 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.

Conditions

Colorectal Cancer

Keywords

Open label; RXC004; Nivolumab; Ring finger protein 43; R-spondin; Efficacy; Safety; Pharmacokinetics

Outcome Measures

Primary Outcomes (2)

• 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)

  The anti-tumour activity of RXC004 monotherapy was evaluated. DCR is defined as the percentage of patients with a BOR of either complete response (CR), partial response (PR) or stable disease (SD) for at least 16 weeks post baseline.

  Up to 28 months

• RXC004+Nivolumab Combination Therapy (Arm B): Objective Response Rate (ORR) Using Each Patient's BOR According to RECIST 1.1

  The anti-tumour activity as a combination therapy of RXC004 +nivolumab was evaluated. ORR is defined as the percentage of patients with a BOR of CR or PR based on local investigator assessment, as defined in RECIST 1.1.

  Up to 28 months

Secondary Outcomes (15)

• Best Percentage Change in Tumor Size

  Up to 28 months

• Progression Free Survival (PFS)

  Up to 28 months

• Duration of Response (DOR)

  Up to 28 months

• RXC004 Monotherapy (Arm A): Objective Response Rate (ORR) Using Investigator Assessments According to RECIST 1.1

  Up to 28 months

• RXC004 + Nivolumab Combination Therapy (Arm B): Disease Control Rate Using Investigator Assessments According to RECIST 1.1

  Up to 28 months

Study Arms (2)

Arm A: RXC004 monotherapy

EXPERIMENTAL

Patients will receive RXC004 (2 mg once daily \[QD\], orally). Patients in Arm A may crossover to Arm B treatment if they have progressive disease on the first Response Evaluation Criteria in Solid Tumours, (RECIST) scan (if Arm B is open at the time of progression).

Drug: RXC004; Biological: Denosumab

Arm B: RXC004 + nivolumab

EXPERIMENTAL

Patients will receive RXC004 (1.5 mg QD, orally) in combination with nivolumab (480 mg every 4 weeks \[q4w\], intravenous \[IV\] infusion). Arm B will be opened once a RP2D for RXC004 in combination with nivolumab is established in the phase I dose escalation study (NCT03447470). RXC004 dose to be used in combination with nivolumab will be based on data from the phase 1 study (NCT03447470).

Drug: RXC004; Biological: Nivolumab; Biological: Denosumab

Interventions

RXC004 DRUG

RXC004 will be administered orally, 2 mg QD (Monotherapy); and 1.5 mg QD (Combination therapy) Dose Formulation: 0.5 mg or 1 mg capsules.

Arm A: RXC004 monotherapy; Arm B: RXC004 + nivolumab

Nivolumab BIOLOGICAL

Nivolumab will be administered via IV infusion, 480 mg q4w.

Arm B: RXC004 + nivolumab

Denosumab BIOLOGICAL

Denosumab will be administered via subcutaneous (SC) injection, 120 mg once every month. Use: Prophylactic

Arm A: RXC004 monotherapy; Arm B: RXC004 + nivolumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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).

You may not qualify if:

• 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

Sponsors & Collaborators

• Redx Pharma Ltd: lead

Study Sites (22)

Providence Medical Foundation

Santa Rosa, California, 95403, United States

Location

Community Health Network Cancer Center North - Community Hospital Network

Indianapolis, Indiana, 46250, United States

Location

OptumCare Cancer Care

Las Vegas, Nevada, 89102, United States

Location

UT MD Anderson Cancer Center

Houston, Texas, 77030-4000, United States

Location

Lumi Research

Kingswood, Texas, 77339, United States

Location

National Cancer Center

Goyang-si, Gyeonggido [Kyonggi-do], 10408, South Korea

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Severance Hospital, Yonsei University Health System - Medical Oncology

Seoul, 3722, South Korea

Location

Asan Medical Center - Oncology

Seoul, 5505, South Korea

Location

Samsung Medical Center - Hematology-Oncology

Seoul, 6351, South Korea

Location

Hospital del Mar

Barcelona, 08003, Spain

Location

Hospital Universitario Vall d'Hebrón

Barcelona, 08035, Spain

Location

Hospital Clìnic de Barcelona

Barcelona, 08036, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Hospital Universitario Virgen del Rocio

Seville, 41013, Spain

Location

Beatson West of Scotland Cancer Centre - Oncology

Glasgow, Scotland, G12 0YN, United Kingdom

Location

Queen Elizabeth Hospital - Clinical Reasearch

Birmingham, B152TH, United Kingdom

Location

University College of London (UCL)

London, NW1 2PG, United Kingdom

Location

The Royal Marsden NHS Foundation Trust - Royal Marsden Hospital

London, SW3 6JJ, United Kingdom

Location

Christie Hospital

Manchester, CB2 0QQ, United Kingdom

Location

Oxford Cancer Centre

Oxford, OX3 7LJ, United Kingdom

Location

The Royal Marsden Hospital (Surrey)

Surrey Quays, SM25PT, United Kingdom

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Nivolumab; Denosumab

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Craig Tilston
• Organization: Redx Pharma Limited

c.tilston@redxpharma.com

+44 (0)7787 983 638

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 25, 2021
• First Posted: May 28, 2021
• Study Start: November 8, 2021
• Primary Completion: April 2, 2024
• Study Completion: April 2, 2024
• Last Updated: April 16, 2025
• Results First Posted: April 16, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

GB (7); US (5); KR (5); ES (5)