Description:
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.
Title
- Brief Title: 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)
- Official Title: A Multi-arm, Phase II, Open-Label, Multicentre Study to Assess the Preliminary Efficacy of RXC004 in Monotherapy and in Combination With Nivolumab, in Patients With Ring Finger Protein 43 (RNF43) or R-spondin (RSPO) Aberrated, Metastatic, Microsatellite Stable, Colorectal Cancer Who Have Progressed Following Therapy With Current Standard of Care (PORCUPINE)
Clinical Trial IDs
- ORG STUDY ID:
RXC004/0002
- NCT ID:
NCT04907539
Conditions
Interventions
| Drug | Synonyms | Arms |
|---|
| RXC004 | | Arm A: RXC004 monotherapy |
| Nivolumab | | Arm B: RXC004 + Nivolumab |
| Denosumab | | Arm A: RXC004 monotherapy |
Purpose
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.
Detailed Description
The study is composed of two arms, RXC004 monotherapy (Arm A) and RXC004 in combination with
Nivolumab (Arm B). 20 evaluable patients will be enrolled in Arm A and 20 eligible patients
in Arm B.
The study will initially open with Arm A; Arm B will be opened once a recommended Phase II
dose (RP2D) for RXC004 in combination with Nivolumab is established in the phase I dose
escalation study (NCT03447470).
Patients in Arm A may be treated with RXC004 + Nivolumab if they have progressive disease on
the 8 week scan (if Arm B is open at the time of progression).
Trial Arms
| Name | Type | Description | Interventions |
|---|
| Arm A: RXC004 monotherapy | Experimental | Patients will receive RXC004 (1.5 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). | |
| 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). | |
Eligibility Criteria
Inclusion Criteria:
- Histological documentation of metastatic (Stage IV) Colorectal cancer (CRC) and
1. Documented tumour tissue aberration in RNF43 and/or RSPO
2. Documented confirmation of microsatellite stable (MSS) status
- Patients must have had documented RECIST1.1 defined 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.
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
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
- Use of any live vaccines against infectious diseases (e.g., influenza, varicella)
within 4 weeks (28 days) of initiation of study treatment
- 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
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | RXC004 Monotherapy: Disease control rate (DCR) using each patients Best Overall Response (BOR) according to Response Evaluation Criteria in Solid Tumours, version 1.1 (RECIST 1.1) |
| Time Frame: | Up to 20 months |
| Safety Issue: | |
| Description: | To assess the anti-tumour activity of RXC004 monotherapy. DCR is defined as the proportion of patients with a BOR of either complete response (CR), partial response (PR) or stable disease (SD) for at least 16 weeks post baseline. |
Secondary Outcome Measures
| Measure: | Percentage change in the sum of target lesions |
| Time Frame: | Up to 24 months |
| Safety Issue: | |
| Description: | To further assess the preliminary efficacy of RXC004 monotherapy and RXC004 + Nivolumab. Percentage change in tumour size will be derived at each visit by the percentage change from baseline in the sum of diameters of target lesions. The best percentage change in tumour size will be the patients value representing the largest decrease (or smallest increase) from baseline in tumour size. |
| Measure: | Duration of response (DoR) |
| Time Frame: | Up to 24 months |
| Safety Issue: | |
| Description: | To further assess the preliminary efficacy of RXC004 monotherapy and RXC004 + Nivolumab. The DoR will be defined as the time from the date of first documented response until date of documented progression or death in the absence of disease progression. If a patient does not progress following a response, then their DOR will be censored at the progression free survival (PFS) censoring time. |
| Measure: | Progression free survival (PFS) |
| Time Frame: | From first dose of study treatment until the date of disease progression or death (Up to 24 months) |
| Safety Issue: | |
| Description: | To further assess the preliminary efficacy of RXC004 monotherapy and RXC004 + Nivolumab. PFS is defined as the time from first dose of study treatment until the date of disease progression or death (by any cause in the absence of progression). |
| Measure: | RXC004 Monotherapy: ORR using investigator assessments according to RECIST 1.1 |
| Time Frame: | Up to 24 months |
| Safety Issue: | |
| Description: | To further assess the preliminary efficacy of RXC004 monotherapy. ORR is defined as the proportion of patients with a BOR of CR or PR, based on local investigator assessment, as defined in RECIST 1.1. |
| Measure: | RXC004 + Nivolumab Combination: DCR using investigator assessments according to RECIST 1.1 |
| Time Frame: | Up to 24 months |
| Safety Issue: | |
| Description: | To further assess the preliminary efficacy of RXC004 + Nivolumab. DCR is defined as the proportion of patients with a BOR of either CR, PR or SD for at least 16 weeks post baseline. |
| Measure: | Overall survival (OS) |
| Time Frame: | Up to 24 months |
| Safety Issue: | |
| Description: | To further assess the preliminary efficacy of RXC004 monotherapy and RXC004 + Nivolumab. OS is defined as the time from first day of study treatment until death due to any cause. |
| Measure: | Maximum observed plasma concentration (Cmax) |
| Time Frame: | At Cycle 0 and Cycle 1 (Each cycle is 28 days in length) |
| Safety Issue: | |
| Description: | To assess the pharmacokinetic (PK) of RXC004 in monotherapy and in combination with Nivolumab. |
| Measure: | Time to Cmax (tmax) |
| Time Frame: | At Cycle 0 and Cycle 1 (Each cycle is 28 days in length) |
| Safety Issue: | |
| Description: | To assess the PK of RXC004 in monotherapy and in combination with Nivolumab. |
| Measure: | Minimum observed concentration across the dosing interval (Cmin) |
| Time Frame: | At each treatment cycle (Each cycle is 28 days in length) |
| Safety Issue: | |
| Description: | To assess the PK of RXC004 in monotherapy and in combination with Nivolumab. |
| Measure: | Terminal rate constant (λz) |
| Time Frame: | At Cycle 0 and Cycle 1 (Each cycle is 28 days in length) |
| Safety Issue: | |
| Description: | To assess the PK of RXC004 in monotherapy and in combination with Nivolumab. |
| Measure: | Terminal half-life (t½) |
| Time Frame: | At Cycle 0 and Cycle 1 (Each cycle is 28 days in length) |
| Safety Issue: | |
| Description: | To assess the PK of RXC004 in monotherapy and in combination with Nivolumab. |
| Measure: | Area under the plasma concentration-time curve from zero to infinity (AUC0-∞) |
| Time Frame: | At Cycle 0 and Cycle 1 (Each cycle is 28 days in length) |
| Safety Issue: | |
| Description: | To assess the PK of RXC004 in monotherapy and in combination with Nivolumab. |
| Measure: | Total plasma clearance after oral administration (CL/F) |
| Time Frame: | At Cycle 0 and Cycle 1 (Each cycle is 28 days in length) |
| Safety Issue: | |
| Description: | To assess the PK of RXC004 in monotherapy and in combination with Nivolumab. |
| Measure: | Apparent volume of distribution after oral administration (Vz/F) |
| Time Frame: | At Cycle 0 and Cycle 1 (Each cycle is 28 days in length) |
| Safety Issue: | |
| Description: | To assess the PK of RXC004 in monotherapy and in combination with Nivolumab. |
| Measure: | Number of patients with adverse events (AEs) |
| Time Frame: | From time of signature of informed consent form throughout the treatment period and until 30 days after the last dose of RXC004 (for RXC004 monotherapy only) or 90 days after the last dose of Nivolumab (for RXC004 + Nivolumab) (up to 24 months) |
| Safety Issue: | |
| Description: | To assess the safety and tolerability profile of RXC004 monotherapy and RXC004 + Nivolumab combination |
Details
| Phase: | Phase 2 |
| Primary Purpose: | Interventional |
| Overall Status: | Not yet recruiting |
| Lead Sponsor: | Redx Pharma Plc |
Trial Keywords
- Open label
- RXC004
- Nivolumab
- Ring finger protein 43
- R-spondin
- Efficacy
- Safety
- Pharmacokinetics
Last Updated
July 7, 2021
