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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.
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 initially opened 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).
Once Arm B is opened, patients who are eligible for both Arm A and Arm B will be randomised 2:1 to Arm B: Arm A in an open-label manner.
Patients in Arm A may be treated with RXC004 + nivolumab if they have progressive disease on the 8 week scan, as long as they are eligible for Arm B and have Sponsor approval.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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). |
|
| 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). |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Best Percentage Change in Tumor Size | The preliminary efficacy of RXC004 monotherapy and combination therapy of RXC004 + nivolumab was evaluated. The best percentage change in tumour size was determined at a patient level. Percentage change in tumour size was 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 was the patients value representing the largest decrease (or smallest increase) from baseline in tumour size. |
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Inclusion Criteria:
Histological documentation of metastatic (Stage IV) Colorectal cancer (CRC) and
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:
Exclusion Criteria:
For patients on RXC004 + nivolumab combination treatment (Arm B or Arm A RXC004 + nivolumab treatment phase):
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Providence Medical Foundation | Santa Rosa | California | 95403 | United States | ||
| Community Health Network Cancer Center North - Community Hospital Network |
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Patients who met the inclusion criteria, and none of the exclusion criteria were enrolled to the study. All study assessments were performed as per the Schedule of Assessment.
This study was conducted from 08 November 2021 to 02 April 2024 at multiple centers in 4 countries (South Korea, Spain, United Kingdom and United States of America).
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| ID | Title | Description |
|---|---|---|
| FG000 | Arm A: RXC004 Monotherapy | Patients received 2 mg of RXC004 monotherapy once daily orally. |
| FG001 | Arm B: RXC004+Nivolumab | Patients received 1.5 mg of RXC004 once daily along with the combination of 480 mg of Nivolumab every 4 weeks orally. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Aug 19, 2022 | Feb 21, 2025 |
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| Nivolumab | Biological | Nivolumab will be administered via IV infusion, 480 mg q4w. |
|
| Denosumab | Biological | Denosumab will be administered via subcutaneous (SC) injection, 120 mg once every month. Use: Prophylactic |
|
| Up to 28 months |
| Progression Free Survival (PFS) | The preliminary efficacy of RXC004 monotherapy and combination therapy of RXC004 + nivolumab was evaluated. 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). | Up to 28 months |
| Duration of Response (DOR) | The preliminary efficacy of RXC004 monotherapy and combination therapy of RXC004 + nivolumab was evaluated. The DOR is as the time from the date of first documented response until date of documented progression or death in the absence of disease progression. DOR was not calculated as 1 patient had PR, and 0 patient had CR. As pre-specified in the SAP that after the review of the available data, DOR would not be summarized and listed. | Up to 28 months |
| RXC004 Monotherapy (Arm A): Objective Response Rate (ORR) Using Investigator Assessments According to RECIST 1.1 | The preliminary efficacy of RXC004 monotherapy 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 |
| RXC004 + Nivolumab Combination Therapy (Arm B): Disease Control Rate Using Investigator Assessments According to RECIST 1.1 | The preliminary efficacy of combination therapy of RXC004 + nivolumab was evaluated. DCR is defined as the percentage of patients with a BOR of either CR, PR or SD for at least 16 weeks post baseline. | Up to 28 months |
| Overall Survival (OS) | The preliminary efficacy of RXC004 monotherapy and combination therapy of RXC004 + nivolumab was evaluated. OS is defined as the time from first day of study treatment until death due to any cause. | Up to 28 months |
| Maximum Observed Plasma Concentration (Cmax) | The pharmacokinetic (PK) (Cmax) of RXC004 in monotherapy and in combination therapy with nivolumab was evaluated. | On Cycle 0 Day 1 (3-7 days cycle in length) and Cycle 1 Day 15 (28 days cycle in length) |
| Time to Maximum Plasma Concentration (Tmax) | The PK (Tmax) of RXC004 in monotherapy and in combination therapy with nivolumab was evaluated. | On Cycle 0 Day 1 (3-7 days cycle in length) and Cycle 1 Day 15 (28 days cycle in length) |
| Minimum Observed Concentration Across the Dosing Interval (Cmin) | The PK (Cmin) of RXC004 in monotherapy and in combination therapy with nivolumab was evaluated. | On Cycle 1 Day 15 (28 days cycle in length) |
| Terminal Rate Constant (λz) | The PK (λz) of RXC004 in monotherapy and in combination therapy with nivolumab was evaluated. | On Cycle 0 Day 1 (3-7 days cycle in length) |
| Terminal Half-life (t½) | The PK (t½) of RXC004 in monotherapy and in combination therapy with nivolumab was evaluated. | On Cycle 0 Day 1 (3-7 days cycle in length) |
| Area Under the Plasma Concentration-time Curve From Zero to Infinity (AUC0-∞) | The PK (AUC0-∞) of RXC004 in monotherapy and in combination therapy with nivolumab was evaluated. | On Cycle 0 Day 1 (3-7 days cycle in length) |
| Total Plasma Clearance After Oral Administration (CL/F) | The PK (CL/F) of RXC004 in monotherapy and in combination therapy with nivolumab was evaluated. | On Cycle 0 Day 1 (3-7 days cycle in length) |
| Apparent Volume of Distribution After Oral Administration (Vz/F) | The PK (Vz/F) of RXC004 in monotherapy and in combination therapy with nivolumab was evaluated. | On Cycle 0 Day 1 (3-7 days cycle in length) |
| Number of Patients With Adverse Events (AEs) | The safety and tolerability profile of RXC004 monotherapy and RXC004 + nivolumab combination was evaluated. The grading scales found in the revised National Cancer Institute Common Terminology Criteria for Adverse events (CTCAE) latest version was utilized for all events with an assigned CTCAE grading. Grade refers to the severity of the AE. The CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental ADL. Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL; Grade 4: Life-threatening, urgent intervention required; Grade 5: Death related to AE. | 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 28 months) |
| Indianapolis |
| Indiana |
| 46250 |
| United States |
| OptumCare Cancer Care | Las Vegas | Nevada | 89102 | United States |
| UT MD Anderson Cancer Center | Houston | Texas | 77030-4000 | United States |
| Lumi Research | Kingswood | Texas | 77339 | United States |
| National Cancer Center | Goyang-si | Gyeonggido [Kyonggi-do] | 10408 | South Korea |
| Seoul National University Hospital | Seoul | 03080 | South Korea |
| Severance Hospital, Yonsei University Health System - Medical Oncology | Seoul | 3722 | South Korea |
| Asan Medical Center - Oncology | Seoul | 5505 | South Korea |
| Samsung Medical Center - Hematology-Oncology | Seoul | 6351 | South Korea |
| Hospital del Mar | Barcelona | 08003 | Spain |
| Hospital Universitario Vall d'Hebrón | Barcelona | 08035 | Spain |
| Hospital Clìnic de Barcelona | Barcelona | 08036 | Spain |
| Hospital Universitario 12 de Octubre | Madrid | 28041 | Spain |
| Hospital Universitario Virgen del Rocio | Seville | 41013 | Spain |
| Beatson West of Scotland Cancer Centre - Oncology | Glasgow | Scotland | G12 0YN | United Kingdom |
| Queen Elizabeth Hospital - Clinical Reasearch | Birmingham | B152TH | United Kingdom |
| University College of London (UCL) | London | NW1 2PG | United Kingdom |
| The Royal Marsden NHS Foundation Trust - Royal Marsden Hospital | London | SW3 6JJ | United Kingdom |
| Christie Hospital | Manchester | CB2 0QQ | United Kingdom |
| Oxford Cancer Centre | Oxford | OX3 7LJ | United Kingdom |
| The Royal Marsden Hospital (Surrey) | Surrey Quays | SM25PT | United Kingdom |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Arm A: RXC004 Monotherapy | Patients received 2 mg of RXC004 monotherapy once daily orally. |
| BG001 | Arm B: RXC004+Nivolumab | Patients received 1.5 mg of RXC004 once daily along with the combination of 480 mg of Nivolumab every 4 weeks orally. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | Year |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race/Ethnicity, Customized | For a single patient of a particular ethnicity, the data was not reported under specific ethnicity in specific arm, rather customized option was used, and the data was reported as "Other" to maintain patient's confidentiality | Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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) | 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. | Evaluable set consisted of all patients who received radiographic assessment at baseline (with measurable disease according to RECIST 1.1), received at least 4 weeks of study treatment and at least 1 post-dose radiographic tumour assessment or progressed or died ahead of the first radiographic assessment. Patients with important protocol deviations that may have impacted outcome were excluded from the population. | Posted | Number | 90% Confidence Interval | Percentage of patients | Up to 28 months |
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| Primary | 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. | Evaluable set consisted of all patients who received radiographic assessment at baseline (with measurable disease according to RECIST 1.1), received at least 4 weeks of study treatment and at least 1 post-dose radiographic tumour assessment or progressed or died ahead of the first radiographic assessment. Patients with important protocol deviations that may have impacted outcome were excluded from the population. | Posted | Number | 90% Confidence Interval | Percentage of patients | Up to 28 months |
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| Secondary | Best Percentage Change in Tumor Size | The preliminary efficacy of RXC004 monotherapy and combination therapy of RXC004 + nivolumab was evaluated. The best percentage change in tumour size was determined at a patient level. Percentage change in tumour size was 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 was the patients value representing the largest decrease (or smallest increase) from baseline in tumour size. | Evaluable set consisted of all patients who received radiographic assessment at baseline (with measurable disease according to RECIST 1.1), received at least 4 weeks of study treatment and at least 1 post-dose radiographic tumour assessment or progressed or died ahead of the first radiographic assessment. Patients with important protocol deviations that may have impacted outcome were excluded from the population. | Posted | Median | Full Range | Percentage change in tumor size | Up to 28 months |
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| Secondary | Progression Free Survival (PFS) | The preliminary efficacy of RXC004 monotherapy and combination therapy of RXC004 + nivolumab was evaluated. 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). | Full analysis set consisted of all patients who were enrolled and received at least one dose of study drug (RXC004). | Posted | Median | 95% Confidence Interval | Months | Up to 28 months |
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| Secondary | Duration of Response (DOR) | The preliminary efficacy of RXC004 monotherapy and combination therapy of RXC004 + nivolumab was evaluated. The DOR is as the time from the date of first documented response until date of documented progression or death in the absence of disease progression. DOR was not calculated as 1 patient had PR, and 0 patient had CR. As pre-specified in the SAP that after the review of the available data, DOR would not be summarized and listed. | Evaluable set consisted of all patients who received radiographic assessment at baseline (with measurable disease according to RECIST 1.1) received at least 4 weeks of treatment and at least 1 post-dose radiographic tumour assessment or progressed or died ahead of the first radiographic assessment. Patients with important protocol deviations that may impact outcome were excluded from population. | Posted | Up to 28 months |
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| Secondary | RXC004 Monotherapy (Arm A): Objective Response Rate (ORR) Using Investigator Assessments According to RECIST 1.1 | The preliminary efficacy of RXC004 monotherapy 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. | Evaluable set consisted of all patients who received radiographic assessment at baseline (with measurable disease according to RECIST 1.1), received at least 4 weeks of study treatment and at least 1 post-dose radiographic tumour assessment or progressed or died ahead of the first radiographic assessment. Patients with important protocol deviations that may impact outcome were excluded from the population. | Posted | Number | 90% Confidence Interval | Percentage of patients | Up to 28 months |
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| Secondary | RXC004 + Nivolumab Combination Therapy (Arm B): Disease Control Rate Using Investigator Assessments According to RECIST 1.1 | The preliminary efficacy of combination therapy of RXC004 + nivolumab was evaluated. DCR is defined as the percentage of patients with a BOR of either CR, PR or SD for at least 16 weeks post baseline. | Evaluable set consisted of all patients who received radiographic assessment at baseline (with measurable disease according to RECIST 1.1), received at least 4 weeks of study treatment and at least 1 post-dose radiographic tumour assessment or progressed or died ahead of the first radiographic assessment. Patients with important protocol deviations that may impact outcome were excluded from the population. | Posted | Number | 90% Confidence Interval | Percentage of patients | Up to 28 months |
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| Secondary | Overall Survival (OS) | The preliminary efficacy of RXC004 monotherapy and combination therapy of RXC004 + nivolumab was evaluated. OS is defined as the time from first day of study treatment until death due to any cause. | Full analysis set consisted of all patients who were enrolled and received at least one dose of study drug (RXC004). | Posted | Median | 95% Confidence Interval | Months | Up to 28 months |
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| Secondary | Maximum Observed Plasma Concentration (Cmax) | The pharmacokinetic (PK) (Cmax) of RXC004 in monotherapy and in combination therapy with nivolumab was evaluated. | The PK Analysis Set included all patients in the full analysis set with at least 1 blood sample. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanogram per milliliter (ng/mL) | On Cycle 0 Day 1 (3-7 days cycle in length) and Cycle 1 Day 15 (28 days cycle in length) |
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| Secondary | Time to Maximum Plasma Concentration (Tmax) | The PK (Tmax) of RXC004 in monotherapy and in combination therapy with nivolumab was evaluated. | The PK Analysis Set included all patients in the full analysis set with at least 1 blood sample. | Posted | Median | Full Range | Hour (h) | On Cycle 0 Day 1 (3-7 days cycle in length) and Cycle 1 Day 15 (28 days cycle in length) |
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| Secondary | Minimum Observed Concentration Across the Dosing Interval (Cmin) | The PK (Cmin) of RXC004 in monotherapy and in combination therapy with nivolumab was evaluated. | The PK Analysis Set included all patients in the full analysis set with at least 1 blood sample. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | On Cycle 1 Day 15 (28 days cycle in length) |
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| Secondary | Terminal Rate Constant (λz) | The PK (λz) of RXC004 in monotherapy and in combination therapy with nivolumab was evaluated. | The PK Analysis Set included all patients in the full analysis set with at least 1 blood sample. | Posted | Geometric Mean | Geometric Coefficient of Variation | 1/hour | On Cycle 0 Day 1 (3-7 days cycle in length) |
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| Secondary | Terminal Half-life (t½) | The PK (t½) of RXC004 in monotherapy and in combination therapy with nivolumab was evaluated. | The PK Analysis Set included all patients in the full analysis set with at least 1 blood sample. | Posted | Geometric Mean | Geometric Coefficient of Variation | hour (h) | On Cycle 0 Day 1 (3-7 days cycle in length) |
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| Secondary | Area Under the Plasma Concentration-time Curve From Zero to Infinity (AUC0-∞) | The PK (AUC0-∞) of RXC004 in monotherapy and in combination therapy with nivolumab was evaluated. | The PK Analysis Set included all patients in the full analysis set with at least 1 blood sample. | Posted | Geometric Mean | Geometric Coefficient of Variation | hour*nanogram/milliliter (h*ng/mL) | On Cycle 0 Day 1 (3-7 days cycle in length) |
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| Secondary | Total Plasma Clearance After Oral Administration (CL/F) | The PK (CL/F) of RXC004 in monotherapy and in combination therapy with nivolumab was evaluated. | The PK Analysis Set included all patients in the full analysis set with at least 1 blood sample. | Posted | Geometric Mean | Geometric Coefficient of Variation | milliliter per hour (mL/h) | On Cycle 0 Day 1 (3-7 days cycle in length) |
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| Secondary | Apparent Volume of Distribution After Oral Administration (Vz/F) | The PK (Vz/F) of RXC004 in monotherapy and in combination therapy with nivolumab was evaluated. | The PK Analysis Set included all patients in the full analysis set with at least 1 blood sample. | Posted | Geometric Mean | Geometric Coefficient of Variation | milliliter (mL) | On Cycle 0 Day 1 (3-7 days cycle in length) |
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| Secondary | Number of Patients With Adverse Events (AEs) | The safety and tolerability profile of RXC004 monotherapy and RXC004 + nivolumab combination was evaluated. The grading scales found in the revised National Cancer Institute Common Terminology Criteria for Adverse events (CTCAE) latest version was utilized for all events with an assigned CTCAE grading. Grade refers to the severity of the AE. The CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental ADL. Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL; Grade 4: Life-threatening, urgent intervention required; Grade 5: Death related to AE. | The safety analysis set consisted of all patients who were enrolled and received at least one dose of study drug (RXC004). | Posted | Count of Participants | Participants | 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 28 months) |
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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 28 months)
Safety Set included all patients who were enrolled and received at least one dose of study drug (RXC004).
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Arm A: RXC004 Monotherapy | Patients received 2 mg of RXC004 monotherapy once daily orally. | 14 | 17 | 3 | 17 | 17 | 17 |
| EG001 | Arm B: RXC004+Nivolumab | Patients received 1.5 mg of RXC004 once daily along with the combination of 480 mg of Nivolumab every 4 weeks orally. | 3 | 8 | 5 | 8 | 8 | 8 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Colitis | Gastrointestinal disorders | MedDRA 26.1 | Non-systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA 26.1 | Non-systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA 26.1 | Non-systematic Assessment |
| |
| Enteritis | Gastrointestinal disorders | MedDRA 26.1 | Non-systematic Assessment |
| |
| Death | General disorders | MedDRA 26.1 | Non-systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA 26.1 | Non-systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA 26.1 | Non-systematic Assessment |
| |
| Blood alkaline phosphatase increased | Investigations | MedDRA 26.1 | Non-systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 26.1 | Non-systematic Assessment |
| |
| Encephalopathy | Nervous system disorders | MedDRA 26.1 | Non-systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 26.1 | Non-systematic Assessment |
| |
| Lymphopenia | Blood and lymphatic system disorders | MedDRA 26.1 | Non-systematic Assessment |
| |
| Bundle branch block right | Cardiac disorders | MedDRA 26.1 | Non-systematic Assessment |
| |
| Hypothyroidism | Endocrine disorders | MedDRA 26.1 | Non-systematic Assessment |
| |
| Dry eye | Eye disorders | MedDRA 26.1 | Non-systematic Assessment |
| |
| Eye pain | Eye disorders | MedDRA 26.1 | Non-systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA 26.1 | Non-systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA 26.1 | Non-systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA 26.1 | Non-systematic Assessment |
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| Abdominal pain | Gastrointestinal disorders | MedDRA 26.1 | Non-systematic Assessment |
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| Constipation | Gastrointestinal disorders | MedDRA 26.1 | Non-systematic Assessment |
| |
| Dyspepsia | Gastrointestinal disorders | MedDRA 26.1 | Non-systematic Assessment |
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| Abdominal pain upper | Gastrointestinal disorders | MedDRA 26.1 | Non-systematic Assessment |
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| Haemorrhoids | Gastrointestinal disorders | MedDRA 26.1 | Non-systematic Assessment |
| |
| Hiatus hernia | Gastrointestinal disorders | MedDRA 26.1 | Non-systematic Assessment |
| |
| Mesenteric vein thrombosis | Gastrointestinal disorders | MedDRA 26.1 | Non-systematic Assessment |
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| Fatigue | General disorders | MedDRA 26.1 | Non-systematic Assessment |
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| Asthenia | General disorders | MedDRA 26.1 | Non-systematic Assessment |
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| Influenza like illness | General disorders | MedDRA 26.1 | Non-systematic Assessment |
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| Chills | General disorders | MedDRA 26.1 | Non-systematic Assessment |
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| Pyrexia | General disorders | MedDRA 26.1 | Non-systematic Assessment |
| |
| Hyperbilirubinaemia | Hepatobiliary disorders | MedDRA 26.1 | Non-systematic Assessment |
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| Hypertransaminasaemia | Hepatobiliary disorders | MedDRA 26.1 | Non-systematic Assessment |
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| Jaundice | Hepatobiliary disorders | MedDRA 26.1 | Non-systematic Assessment |
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| Portal vein thrombosis | Hepatobiliary disorders | MedDRA 26.1 | Non-systematic Assessment |
| |
| Lower respiratory tract infection | Infections and infestations | MedDRA 26.1 | Non-systematic Assessment |
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| Urinary tract infection | Infections and infestations | MedDRA 26.1 | Non-systematic Assessment |
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| COVID-19 | Infections and infestations | MedDRA 26.1 | Non-systematic Assessment |
| |
| Cytomegalovirus infection | Infections and infestations | MedDRA 26.1 | Non-systematic Assessment |
| |
| Escherichia urinary tract infection | Infections and infestations | MedDRA 26.1 | Non-systematic Assessment |
| |
| Folliculitis | Infections and infestations | MedDRA 26.1 | Non-systematic Assessment |
| |
| Lower respiratory tract infection viral | Infections and infestations | MedDRA 26.1 | Non-systematic Assessment |
| |
| Osteomyelitis | Infections and infestations | MedDRA 26.1 | Non-systematic Assessment |
| |
| Rhinitis | Infections and infestations | MedDRA 26.1 | Non-systematic Assessment |
| |
| Sepsis | Infections and infestations | MedDRA 26.1 | Non-systematic Assessment |
| |
| Tonsillitis | Infections and infestations | MedDRA 26.1 | Non-systematic Assessment |
| |
| Stoma prolapse | Injury, poisoning and procedural complications | MedDRA 26.1 | Non-systematic Assessment |
| |
| Weight decreased | Investigations | MedDRA 26.1 | Non-systematic Assessment |
| |
| Blood bilirubin increased | Investigations | MedDRA 26.1 | Non-systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA 26.1 | Non-systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA 26.1 | Non-systematic Assessment |
| |
| Blood alkaline phosphatase increased | Investigations | MedDRA 26.1 | Non-systematic Assessment |
| |
| Amylase increased | Investigations | MedDRA 26.1 | Non-systematic Assessment |
| |
| C-reactive protein increased | Investigations | MedDRA 26.1 | Non-systematic Assessment |
| |
| Blood creatinine increased | Investigations | MedDRA 26.1 | Non-systematic Assessment |
| |
| Blood fibrinogen increased | Investigations | MedDRA 26.1 | Non-systematic Assessment |
| |
| Carcinoembryonic antigen increased | Investigations | MedDRA 26.1 | Non-systematic Assessment |
| |
| Ejection fraction decreased | Investigations | MedDRA 26.1 | Non-systematic Assessment |
| |
| Gamma-glutamyltransferase increased | Investigations | MedDRA 26.1 | Non-systematic Assessment |
| |
| Gastric pH decreased | Investigations | MedDRA 26.1 | Non-systematic Assessment |
| |
| Lipase increased | Investigations | MedDRA 26.1 | Non-systematic Assessment |
| |
| Protein urine present | Investigations | MedDRA 26.1 | Non-systematic Assessment |
| |
| Urine calcium decreased | Investigations | MedDRA 26.1 | Non-systematic Assessment |
| |
| Vitamin D decreased | Investigations | MedDRA 26.1 | Non-systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA 26.1 | Non-systematic Assessment |
| |
| Hypomagnesaemia | Metabolism and nutrition disorders | MedDRA 26.1 | Non-systematic Assessment |
| |
| Hypocalcaemia | Metabolism and nutrition disorders | MedDRA 26.1 | Non-systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA 26.1 | Non-systematic Assessment |
| |
| Hypophosphataemia | Metabolism and nutrition disorders | MedDRA 26.1 | Non-systematic Assessment |
| |
| Hyperammonaemia | Metabolism and nutrition disorders | MedDRA 26.1 | Non-systematic Assessment |
| |
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA 26.1 | Non-systematic Assessment |
| |
| Hyperkalaemia | Metabolism and nutrition disorders | MedDRA 26.1 | Non-systematic Assessment |
| |
| Hypoalbuminaemia | Metabolism and nutrition disorders | MedDRA 26.1 | Non-systematic Assessment |
| |
| Hypoglycaemia | Metabolism and nutrition disorders | MedDRA 26.1 | Non-systematic Assessment |
| |
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA 26.1 | Non-systematic Assessment |
| |
| Malnutrition | Metabolism and nutrition disorders | MedDRA 26.1 | Non-systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 26.1 | Non-systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 26.1 | Non-systematic Assessment |
| |
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA 26.1 | Non-systematic Assessment |
| |
| Coccydynia | Musculoskeletal and connective tissue disorders | MedDRA 26.1 | Non-systematic Assessment |
| |
| Groin pain | Musculoskeletal and connective tissue disorders | MedDRA 26.1 | Non-systematic Assessment |
| |
| Muscular weakness | Musculoskeletal and connective tissue disorders | MedDRA 26.1 | Non-systematic Assessment |
| |
| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA 26.1 | Non-systematic Assessment |
| |
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA 26.1 | Non-systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA 26.1 | Non-systematic Assessment |
| |
| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA 26.1 | Non-systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 26.1 | Non-systematic Assessment |
| |
| Pain in jaw | Musculoskeletal and connective tissue disorders | MedDRA 26.1 | Non-systematic Assessment |
| |
| Acrochordon | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 26.1 | Non-systematic Assessment |
| |
| Dysgeusia | Nervous system disorders | MedDRA 26.1 | Non-systematic Assessment |
| |
| Lethargy | Nervous system disorders | MedDRA 26.1 | Non-systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA 26.1 | Non-systematic Assessment |
| |
| Ageusia | Nervous system disorders | MedDRA 26.1 | Non-systematic Assessment |
| |
| Balance disorder | Nervous system disorders | MedDRA 26.1 | Non-systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA 26.1 | Non-systematic Assessment |
| |
| Loss of consciousness | Nervous system disorders | MedDRA 26.1 | Non-systematic Assessment |
| |
| Neurotoxicity | Nervous system disorders | MedDRA 26.1 | Non-systematic Assessment |
| |
| Seizure | Nervous system disorders | MedDRA 26.1 | Non-systematic Assessment |
| |
| Vocal cord paralysis | Nervous system disorders | MedDRA 26.1 | Non-systematic Assessment |
| |
| Depressed mood | Psychiatric disorders | MedDRA 26.1 | Non-systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA 26.1 | Non-systematic Assessment |
| |
| Mental status changes | Psychiatric disorders | MedDRA 26.1 | Non-systematic Assessment |
| |
| Acute kidney injury | Renal and urinary disorders | MedDRA 26.1 | Non-systematic Assessment |
| |
| Postmenopausal haemorrhage | Reproductive system and breast disorders | MedDRA 26.1 | Non-systematic Assessment |
| |
| Vulvovaginal dryness | Reproductive system and breast disorders | MedDRA 26.1 | Non-systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 26.1 | Non-systematic Assessment |
| |
| Acute respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA 26.1 | Non-systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 26.1 | Non-systematic Assessment |
| |
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA 26.1 | Non-systematic Assessment |
| |
| Productive cough | Respiratory, thoracic and mediastinal disorders | MedDRA 26.1 | Non-systematic Assessment |
| |
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA 26.1 | Non-systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 26.1 | Non-systematic Assessment |
| |
| Dry skin | Skin and subcutaneous tissue disorders | MedDRA 26.1 | Non-systematic Assessment |
| |
| Nail ridging | Skin and subcutaneous tissue disorders | MedDRA 26.1 | Non-systematic Assessment |
| |
| Nail discolouration | Skin and subcutaneous tissue disorders | MedDRA 26.1 | Non-systematic Assessment |
| |
| Dermatitis | Skin and subcutaneous tissue disorders | MedDRA 26.1 | Non-systematic Assessment |
| |
| Nail disorder | Skin and subcutaneous tissue disorders | MedDRA 26.1 | Non-systematic Assessment |
| |
| Onychoclasis | Skin and subcutaneous tissue disorders | MedDRA 26.1 | Non-systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA 26.1 | Non-systematic Assessment |
| |
| Skin ulcer | Skin and subcutaneous tissue disorders | MedDRA 26.1 | Non-systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA 26.1 | Non-systematic Assessment |
| |
| Thrombosis | Vascular disorders | MedDRA 26.1 | Non-systematic Assessment |
|
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Craig Tilston | Redx Pharma Limited | +44 (0)7787 983 638 | c.tilston@redxpharma.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | May 30, 2024 | Feb 21, 2025 | SAP_001.pdf |
Not provided
| ID | Term |
|---|---|
| D015179 | Colorectal Neoplasms |
| ID | Term |
|---|---|
| D007414 | Intestinal Neoplasms |
| D005770 | Gastrointestinal Neoplasms |
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D004066 | Digestive System Diseases |
| D005767 | Gastrointestinal Diseases |
| D003108 | Colonic Diseases |
| D007410 | Intestinal Diseases |
| D012002 | Rectal Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D000077594 | Nivolumab |
| D000069448 | Denosumab |
| ID | Term |
|---|---|
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
Not provided
Not provided
| Male |
|
| Not Stated |
|
| Unknown |
|
| Other |
|
|
| Units | Counts |
|---|
| Participants |
|
|
|
| Participants |
|
|
|
|
|
|
|
|
|
|
|
|
Patients received 1.5 mg of RXC004 once daily along with the combination of 480 mg of Nivolumab every 4 weeks orally. |
|
|