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The purpose of this study is to determine the safety and tolerability of RXC004 as monotherapy and in combination with Nivolumab in patients with advanced malignancies. In order to define the doses and schedules for further clinical evaluation.
The study will consist of an ascending monotherapy dose, the doses are pre-defined.
The decision to escalate will be made upon the assessment of safety and tolerability data in the first cycle of treatment.
Module 1 will commence with a 3+3 dose escalation design up to a recommended Phase 2 monotherapy dose. Patients being monitored for dose limiting toxicities at each dose level.
Characterisation of the PK profile, MTD and/or recommended Phase 2 dose will be defined on the emerging data.
Module 2: RXC004 and Nivolumab - Follows a similar 3+3 dose escalation design using RXC004 plus Nivolumab. The MTD and/or Phase 2 dose will be defined based on the PK profile, emerging safety and the appearance of any dose limiting toxicities.
Module 3: Intermittent dose schedules of RXC004 will be investigated. The intermittent schedules will utilize the module 1 dose which was shown to be safe and tolerated when used continuously. Characterisation of the PK profile; Wnt pathway inhibition; incidence/severity of Wnt pathway related AEs and anti-tumor activity will be evaluated at 2 different dosing schedules.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Module 1 Arm 1 - Monotherapy RXC004 (0.5 mg) | Experimental | Patients were given 0.5 mg RXC004 and monitored for Dose Limiting Toxicities. |
|
| Module 2 Arm 1 - RXC004 (1.0 mg) plus Nivolumab | Experimental | Patients were given 1.0 mg RXC004 in combination with a standard dose of Nivolumab and monitored for Dose Limiting Toxicities. |
|
| Module 3 - Intermittent schedules of monotherapy RXC004 | Experimental | Patients were given 2.0 mg RXC004. The patients were treated for 2 weeks at the same dose, followed by 1 week off for a 21 day cycle. |
|
| Module 1 Arm 2 - Monotherapy RXC004 (1.0 mg) | Experimental | Patients were given 1.0 mg RXC004 and monitored for Dose Limiting Toxicities. |
|
| Module 1 Arm 3 - Monotherapy RXC004 (1.5 mg) | Experimental | Patients were given 1.5 mg RXC004 and monitored for Dose Limiting Toxicities. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| RXC004 | Drug | RXC004 is taken orally, inhibits porcupine (PORCN) and interacts with the wnt signalling pathway. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Module 1 - Safety and Tolerability of RXC004 by Assessment of Whether Any Dose Limiting Toxicities (DLT) Arise From First Dose Until the End of 21 Days of Continuous Dosing: | A DLT was defined as an adverse event or abnormal laboratory value. Haematological toxicity of CTCAE grade 4 or higher for more than 4 consecutive days. Grade 3 neutropenia of any duration accompanied by fever 38.5 degrees Celsius or higher. Grade 3 thrombocytopaenia with bleeding. Any other confirmed haematological toxicity CTCAE grade 4 or higher. Non-haematological toxicity CTCAE grade 3 or higher. Any other toxicity that is judged to be a DLT by the Safety Review Committee. An AE resulting in disrupted dosing >14 days. | AE data was collected after each cycle and until 30-day follow-up visit after study exit. The DLT period were assessed from the first dose until the end of 21 days of continuous dosing in each cycle until a Maximum Tolerated Dose (MTD) was identified. |
| Module 2 - Safety and Tolerability of RXC004 in Combination With Nivolumab by Assessment of Whether Any Dose Limiting Toxicities (DLT) Arise From First Dose Until the End of 28 Days of Continuous Dosing. | A DLT is defined as an adverse event or abnormal laboratory value. Haematological toxicity of CTCAE grade 4 or higher for more than 4 consecutive days. Grade 3 neutropenia of any duration accompanied by fever 38.5 degrees Celsius or higher. Grade 3 thrombocytopaenia with bleeding. Any other confirmed haematological toxicity CTCAE grade 4 or higher. Non-haematological toxicity CTCAE grade 3 or higher. Any other toxicity that is judged to be a DLT by the Safety Review Committee. An AE resulting in disrupted dosing >14 days. Any grade 3 or higher immune-related adverse events | The DLT period will be assessed from the first dose until the end of 28 days of continuous dosing. This will be completed for each dose level until a Maximum Tolerated Dose (MTD) is identified. Estimated time 12 Months in total |
| Module 3 - Safety and Tolerability of RXC004 at Intermittent Dosing Schedule. | Haematological toxicity of CTCAE grade 4 or higher present for more than 4 consecutive days. Grade 3 neutropenia of any duration accompanied by fever 38.5 degrees Celsius or higher. Grade 3 thrombocytopaenia with bleeding. Any other confirmed haematological toxicity CTCAE grade 4 or higher. Non-haematological toxicity CTCAE grade 3 or higher. Any other toxicity that is judged to be a DLT by the Safety Review Committee. An AE resulting in disrupted dosing >14 days. Any grade 3 or higher immune-related adverse events. |
| Measure | Description | Time Frame |
|---|---|---|
| Module 1 - PK Profile - AUC on Cycle 0 Day 1 (C0D1) | Area under the Curve, AUC (0-24) for RXC004 was calculated from the measurement of mean plasma concentration of RXC004 at various time points from 0 - 96 hours following single dose on Cycle 0 Day1. | Samples were analyzed from 0 - 96 hours after administration to evaluate PK parameters on Cycle 0 Day 1. |
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(Summarized due to limitation of characters)
Inclusion Criteria:
Exclusion Criteria:
In addition for Module 2
In addition to Module 3
Patients with Wnt ligand-dependent solid tumours, defined as:
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| Name | Affiliation | Role |
|---|---|---|
| Natalie Cook | The Christie NHS Foundation Trust | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Royal Marsden Hospital, Institute of Cancer Research | Sutton | Surrey | SM2 5PT | United Kingdom | ||
| Guys Hospital |
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In Module 1, participants enrolled, into 6 arms at different dose levels: 0.5 mg; 1 mg; 1.5 mg; 2 mg; 3 mg; 10 mg.
In Module 2, participants enrolled, into 2 arms at different dose levels (1.0 mg and 1.5 mg) of RXC004 in combination with Nivolumab.
In Module 3, the enrolled participants received a dose of 2.0 mg of RXC004 at 2 weeks on/1 week off.
Participants were enrolled into one of the modules of the study.
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| ID | Title | Description |
|---|---|---|
| FG000 | Module 1 Arm 1 - Monotherapy RXC004 (0.5 mg) | Patients were given 0.5 mg RXC004 monitored for Dose Limiting Toxicities. |
| FG001 | Module 1 Arm 2 - Monotherapy RXC004 (1.0 mg) | Patients were given 1.0 mg RXC004 monitored for Dose Limiting Toxicities. |
| FG002 | Module 1 Arm 3 - Monotherapy RXC004 (1.5 mg) | Patients were given 1.5 mg RXC004 and monitored for Dose Limiting Toxicities. |
| FG003 | Module 1 Arm 4 - Monotherapy RXC004 (2.0 mg) | Patients were given 2.0 mg RXC004 and monitored for Dose Limiting Toxicities. |
| FG004 | Module 1 Arm 5 - Monotherapy RXC004 (3.0 mg) | Patients were given 3.0 mg RXC004 and monitored for Dose Limiting Toxicities. |
| FG005 | Module 1 Arm 6 - Monotherapy RXC004 (10.0 mg) | Patients were given 10.0 mg RXC004 and monitored for Dose Limiting Toxicities. |
| FG006 | Module 2 Arm 1 - RXC004 (1.0 mg) Plus Nivolumab | Patients were given 1.0 mg RXC004 in combination with a standard dose of Nivolumab and monitored for Dose Limiting Toxicities. |
| FG007 | Module 2 Arm 2 - RXC004 (1.5 mg) Plus Nivolumab | Patients were given 1.5 mg RXC004 in combination with a standard dose of Nivolumab and monitored for Dose Limiting Toxicities. |
| FG008 | Module 3 - Intermittent Schedules of Monotherapy RXC004 | Patients were given RXC004 at 2 mg once a day (QD) for 2 weeks, followed by 1 week off for 21 day treatment cycles. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
The Baseline Analysis Population described here per module include: In Module 1, participants enrolled, into 6 arms at different dose levels: 0.5 mg; 1 mg; 1.5 mg; 2 mg; 3 mg; 10 mg.
In Module 2, participants enrolled, into 2 arms at different dose levels (1.0 mg and 1.5 mg) of RXC004 in combination with Nivolumab.
In Module 3, the enrolled participants received a dose of 2.0 mg of RXC004 at 2 weeks on/1 week off.
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| ID | Title | Description |
|---|---|---|
| BG000 | Module 1 Arm 1 - Monotherapy RXC004 (0.5 mg) | Patients were given 0.5 mg RXC004 monitored for Dose Limiting Toxicities. |
| BG001 | Module 1 Arm 2 - Monotherapy RXC004 (1.0 mg) | Patients were given 1.0 mg RXC004 monitored for Dose Limiting Toxicities. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of 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 | Module 1 - Safety and Tolerability of RXC004 by Assessment of Whether Any Dose Limiting Toxicities (DLT) Arise From First Dose Until the End of 21 Days of Continuous Dosing: | A DLT was defined as an adverse event or abnormal laboratory value. Haematological toxicity of CTCAE grade 4 or higher for more than 4 consecutive days. Grade 3 neutropenia of any duration accompanied by fever 38.5 degrees Celsius or higher. Grade 3 thrombocytopaenia with bleeding. Any other confirmed haematological toxicity CTCAE grade 4 or higher. Non-haematological toxicity CTCAE grade 3 or higher. Any other toxicity that is judged to be a DLT by the Safety Review Committee. An AE resulting in disrupted dosing >14 days. | RXC004 monotherapy was evaluated at 6 increasing doses. | Posted | Count of Participants | Participants | AE data was collected after each cycle and until 30-day follow-up visit after study exit. The DLT period were assessed from the first dose until the end of 21 days of continuous dosing in each cycle until a Maximum Tolerated Dose (MTD) was identified. |
|
AE data was collected after each cycle and until 30-day follow-up visit after the last dose or study exit. The median duration of exposure for Module 1 was 7.0 weeks across all dose cohorts. For Module 2 - 7.1 weeks in the 1.0 mg group and 8.4 weeks in the 1.5 mg group; Module 3 - 5.0 weeks.
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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 | Module 1 Arm 1 - Monotherapy RXC004 (0.5 mg) | Patients were given 0.5 mg RXC004 monitored for Dose Limiting Toxicities. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Lung Infection/Pneumonia | Infections and infestations | MedDRA 24.1 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Craig Tilston | Redx Pharma Limited | +44 (0)7787 983 638 | c.tilston@redxpharma.com |
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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 | Sep 16, 2022 | Oct 8, 2024 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Aug 11, 2023 | Oct 8, 2024 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D009369 | Neoplasms |
| D001661 | Biliary Tract Neoplasms |
| D013953 | Thymus Neoplasms |
| ID | Term |
|---|---|
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
| D001660 | Biliary Tract Diseases |
| D004066 | Digestive System Diseases |
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| ID | Term |
|---|---|
| D000077594 | Nivolumab |
| ID | Term |
|---|---|
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
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Module 1 monotherapy Dose escalation in those patients with advanced solid tumors while being monitored for safety and dose-limiting toxicity. This module will provide information on dosing and schedules for further module(s).
Module 2 will commence by enrolling patients with advanced solid tumors into a monotherapy dose escalation, in combination with a fixed dose of nivolumab (a known anti-cancer treatment). This module will provide information and safety and tolerability of the study drug or in combination with the anti-cancer treatment.
Module 3 will investigate the pharmacokinetic, Wnt pathway inhibition, incidence/severity of Wnt pathway related adverse events and anti-tumour activity of RXC004 when given at 2 different intermittent dosing schedules in selected patients with Wnt ligand dependent advanced tumours.
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Open label design
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| Module 1 Arm 4 - Monotherapy RXC004 (2.0 mg) |
| Experimental |
Patients were given 2.0 mg RXC004 and monitored for Dose Limiting Toxicities. |
|
| Module 1 Arm 5 - Monotherapy RXC004 (3.0 mg) | Experimental | Patients were given 3.0 mg RXC004 and monitored for Dose Limiting Toxicities. |
|
| Module 1 Arm 6 - Monotherapy RXC004 (10.0 mg) | Experimental | Patients were given 10.0 mg RXC004 and monitored for Dose Limiting Toxicities. |
|
| Module 2 Arm 2 - RXC004 (1.5 mg) plus Nivolumab | Experimental | Patients were given 1.5 mg RXC004 in combination with a standard dose of Nivolumab and monitored for Dose Limiting Toxicities. |
|
| Nivolumab | Drug | RXC004 is taken orally, inhibits porcupine (PORCN) and interacts with the wnt signalling pathway. Nivolumab is a fully human monoclonal immunoglobulin G4 antibody to PD-1 |
|
| The assessment period will be from the first dose until the end of 21 days of intermittent dosing or within 7 days of IP discontinuation. |
| Module 1 - PK Profile - C24 on Cycle 0 Day 1 (C0D1) | Mean Plasma concentration of RXC004 at 24 h post-dose calculated from the measurement of mean RXC004 concentrations at various time points from 0 - 96 hours following single dose on Cycle 0 Day1.. | Samples were analyzed from 0 - 96 hours after administration to evaluate PK parameters on Cycle 0 Day 1. |
| Module 1 - PK Profile - Cmax on Cycle 0 Day 1 (C0D1) | Maximum plasma concentration (Cmax) of RXC004 following single dose calculated from the measurement of mean plasma concentration of RXC004 at various time points from 0 - 96 hours following single dose on Cycle 0 Day1.. | Samples were analyzed from 0 - 96 hours after administration to evaluate PK parameters on Cycle 0 Day 1. |
| Module 1 - PK Profile - Half-life From PK Analysis on Cycle 0 Day 1 (C0D1) | Half-life of RXC004 following single dose on Cycle 0 Day1 calculated from the measurement of mean plasma concentration of RXC004 at various time points from 0 - 96 hours following single dose on Cycle 0 Day1.. | Samples were analyzed from 0 - 96 hours after administration to evaluate PK parameters on Cycle 0 Day 1. |
| Module 2 - PK Profile - AUC on Cycle 0 Day 1 (C0D1) | AUC was calculated from the measurement of mean plasma concentration of RXC004 at various time points from 0 - 48 hours following single dose of RXC004 in combination with Nivolumab on Cycle 0 Day1. | Samples were analyzed from 0 - 48 hours after administration to evaluate PK parameters on Cycle 0 Day 1. |
| Module 2 - PK Profile - C24 on Cycle 0 Day 1 (C0D1) | Mean Plasma concentration of RXC004 at 24 h post-dose when given in combination with Nivolumab. | Samples were analyzed from 0 - 48 hours after administration to evaluate PK parameters on Cycle 0 Day 1. |
| Module 2 - PK Profile - Cmax on Cycle 0 Day 1 (C0D1) | Maximum plasma concentration (Cmax) of RXC004 following single dose on Cycle 0 Day1 when given in combination with Nivolumab.. | Samples were analyzed from 0 - 48 hours after administration to evaluate PK parameters on Cycle 0 Day 1. |
| Module 2 - PK Profile - Half-life From PK Analysis on Cycle 0 Day 1 (C0D1) | Half-life of RXC004 following single dose on Cycle 0 Day1 when given in combination with Nivolumab. | Samples were analyzed from 0 - 48 hours after administration to evaluate PK parameters on Cycle 0 Day 1. |
| Module 3 - PK Profile - AUC on Cycle 0 Day 1 (C0D1) | AUC was calculated from the measurement of mean plasma concentration of RXC004 at various time points from 0 - 48 hours following single dose of RXC004 | Samples were analyzed from 0 - 48 hours after administration to evaluate PK parameters on Cycle 0 Day 1. |
| Module 3 - PK Profile - C24 on Cycle 0 Day 1 (C0D1) | Mean Plasma concentration of RXC004 at 24 h post-dose | Samples were analyzed from 0 - 48 hours after administration to evaluate PK parameters on Cycle 0 Day 1. |
| Module 3 - PK Profile - Cmax on Cycle 0 Day 1 (C0D1) | Maximum plasma concentration (Cmax) of RXC004 following single dose | Samples were analyzed from 0 - 48 hours after administration to evaluate PK parameters on Cycle 0 Day 1. |
| Module 3 - PK Profile - Half-life on Cycle 0 Day 1 (C0D1) | Half-life of RXC004 following single dose. | Cycle 0 Day 1 |
| London |
| SE1 9RT |
| United Kingdom |
| The Christie NHS Foundation Trust | Manchester | M20 4BX | United Kingdom |
| Sir Bobby Robson Cancer Trials Research Centre | Newcastle | NE77DN | United Kingdom |
| Department of Oncology | Oxford | OX3 7LE | United Kingdom |
| Withdrawal by Subject |
|
| Treatment discontinued |
|
| BG002 | Module 1 Arm 3 - Monotherapy RXC004 (1.5 mg) | Patients were given 1.5 mg RXC004 and monitored for Dose Limiting Toxicities. |
| BG003 | Module 1 Arm 4 - Monotherapy RXC004 (2.0 mg) | Patients were given 2.0 mg RXC004 and monitored for Dose Limiting Toxicities. |
| BG004 | Module 1 Arm 5 - Monotherapy RXC004 (3.0 mg) | Patients were given 3.0 mg RXC004 and monitored for Dose Limiting Toxicities. |
| BG005 | Module 1 Arm 6 - Monotherapy RXC004 (10.0 mg) | Patients were given 10.0 mg RXC004 and monitored for Dose Limiting Toxicities. |
| BG006 | Module 2 Arm 1 - RXC004 (1.0 mg) Plus Nivolumab | Patients were given 1.0 mg RXC004 in combination with a standard dose of Nivolumab and monitored for Dose Limiting Toxicities. |
| BG007 | Module 2 Arm 2 - RXC004 (1.5 mg) Plus Nivolumab | Patients were given 1.5 mg RXC004 in combination with a standard dose of Nivolumab and monitored for Dose Limiting Toxicities. |
| BG008 | Intermittent Schedules of Monotherapy RXC004 - Module 3 | Patients were given RXC004 at 2 mg once a day (QD). Patients were treated for 2 weeks at the same dose, followed by 1 week off for 21 day treatment cycles. |
| BG009 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Median | Full Range | Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| OG000 |
| Module 1 Arm 1 - Monotherapy RXC004 (0.5 mg) |
Patients were given 0.5 mg RXC004 monitored for Dose Limiting Toxicities. |
| OG001 | Module 1 Arm 2 - Monotherapy RXC004 (1.0 mg) | Patients were given 1.0 mg RXC004 and monitored for Dose Limiting Toxicities. |
| OG002 | Module 1 Arm 3 - Monotherapy RXC004 (1.5 mg) | Patients were given 1.5 mg RXC004 and monitored for Dose Limiting Toxicities. |
| OG003 | Module 1 Arm 4 - Monotherapy RXC004 (2.0 mg) | Patients were given 2.0 mg RXC004 and monitored for Dose Limiting Toxicities. |
| OG004 | Module 1 Arm 5 - Monotherapy RXC004 (3.0 mg) | Patients were given 3.0 mg RXC004 and monitored for Dose Limiting Toxicities. |
| OG005 | Module 1 Arm 6 - Monotherapy RXC004 (10.0 mg) | Patients were given 10.0 mg RXC004 and monitored for Dose Limiting Toxicities. |
|
|
| Primary | Module 2 - Safety and Tolerability of RXC004 in Combination With Nivolumab by Assessment of Whether Any Dose Limiting Toxicities (DLT) Arise From First Dose Until the End of 28 Days of Continuous Dosing. | A DLT is defined as an adverse event or abnormal laboratory value. Haematological toxicity of CTCAE grade 4 or higher for more than 4 consecutive days. Grade 3 neutropenia of any duration accompanied by fever 38.5 degrees Celsius or higher. Grade 3 thrombocytopaenia with bleeding. Any other confirmed haematological toxicity CTCAE grade 4 or higher. Non-haematological toxicity CTCAE grade 3 or higher. Any other toxicity that is judged to be a DLT by the Safety Review Committee. An AE resulting in disrupted dosing >14 days. Any grade 3 or higher immune-related adverse events | RXC004 (at 2 doses) was evaluated in combination with Nivolumab. | Posted | Count of Participants | Participants | The DLT period will be assessed from the first dose until the end of 28 days of continuous dosing. This will be completed for each dose level until a Maximum Tolerated Dose (MTD) is identified. Estimated time 12 Months in total |
|
|
|
| Primary | Module 3 - Safety and Tolerability of RXC004 at Intermittent Dosing Schedule. | Haematological toxicity of CTCAE grade 4 or higher present for more than 4 consecutive days. Grade 3 neutropenia of any duration accompanied by fever 38.5 degrees Celsius or higher. Grade 3 thrombocytopaenia with bleeding. Any other confirmed haematological toxicity CTCAE grade 4 or higher. Non-haematological toxicity CTCAE grade 3 or higher. Any other toxicity that is judged to be a DLT by the Safety Review Committee. An AE resulting in disrupted dosing >14 days. Any grade 3 or higher immune-related adverse events. | RXC004 was evaluated at a dose of 2 mg monotherapy administered as an intermittent schedule of 2 weeks on/1 week off dosing | Posted | Count of Participants | Participants | The assessment period will be from the first dose until the end of 21 days of intermittent dosing or within 7 days of IP discontinuation. |
|
|
|
| Secondary | Module 1 - PK Profile - AUC on Cycle 0 Day 1 (C0D1) | Area under the Curve, AUC (0-24) for RXC004 was calculated from the measurement of mean plasma concentration of RXC004 at various time points from 0 - 96 hours following single dose on Cycle 0 Day1. | PK parameter AUC (0-24) was analyzed at various dose levels ranging from 0.5 - 10 mg. | Posted | Mean | Standard Deviation | h*ng/ml | Samples were analyzed from 0 - 96 hours after administration to evaluate PK parameters on Cycle 0 Day 1. |
|
|
|
| Secondary | Module 1 - PK Profile - C24 on Cycle 0 Day 1 (C0D1) | Mean Plasma concentration of RXC004 at 24 h post-dose calculated from the measurement of mean RXC004 concentrations at various time points from 0 - 96 hours following single dose on Cycle 0 Day1.. | PK parameter, C24, was analyzed at various dose levels ranging from 0.5 - 10 mg. | Posted | Mean | Standard Deviation | ng/ml | Samples were analyzed from 0 - 96 hours after administration to evaluate PK parameters on Cycle 0 Day 1. |
|
|
|
| Secondary | Module 1 - PK Profile - Cmax on Cycle 0 Day 1 (C0D1) | Maximum plasma concentration (Cmax) of RXC004 following single dose calculated from the measurement of mean plasma concentration of RXC004 at various time points from 0 - 96 hours following single dose on Cycle 0 Day1.. | PK parameter Cmax was analyzed at various dose levels ranging from 0.5 - 10 mg. | Posted | Mean | Standard Deviation | ng/ml | Samples were analyzed from 0 - 96 hours after administration to evaluate PK parameters on Cycle 0 Day 1. |
|
|
|
| Secondary | Module 1 - PK Profile - Half-life From PK Analysis on Cycle 0 Day 1 (C0D1) | Half-life of RXC004 following single dose on Cycle 0 Day1 calculated from the measurement of mean plasma concentration of RXC004 at various time points from 0 - 96 hours following single dose on Cycle 0 Day1.. | PK parameter Half-life was analyzed at various dose levels ranging from 0.5 - 10 mg. | Posted | Median | Full Range | hours | Samples were analyzed from 0 - 96 hours after administration to evaluate PK parameters on Cycle 0 Day 1. |
|
|
|
| Secondary | Module 2 - PK Profile - AUC on Cycle 0 Day 1 (C0D1) | AUC was calculated from the measurement of mean plasma concentration of RXC004 at various time points from 0 - 48 hours following single dose of RXC004 in combination with Nivolumab on Cycle 0 Day1. | PK parameter AUC(0-24) was analyzed at the indicated dose levels. | Posted | Mean | Standard Deviation | h*ng/ml | Samples were analyzed from 0 - 48 hours after administration to evaluate PK parameters on Cycle 0 Day 1. |
|
|
|
| Secondary | Module 2 - PK Profile - C24 on Cycle 0 Day 1 (C0D1) | Mean Plasma concentration of RXC004 at 24 h post-dose when given in combination with Nivolumab. | PK parameter C24 was analyzed at the indicated dose levels. | Posted | Mean | Standard Deviation | ng/ml | Samples were analyzed from 0 - 48 hours after administration to evaluate PK parameters on Cycle 0 Day 1. |
|
|
|
| Secondary | Module 2 - PK Profile - Cmax on Cycle 0 Day 1 (C0D1) | Maximum plasma concentration (Cmax) of RXC004 following single dose on Cycle 0 Day1 when given in combination with Nivolumab.. | PK parameter Cmax was analyzed at the indicated dose levels. | Posted | Mean | Standard Deviation | ng/ml | Samples were analyzed from 0 - 48 hours after administration to evaluate PK parameters on Cycle 0 Day 1. |
|
|
|
| Secondary | Module 2 - PK Profile - Half-life From PK Analysis on Cycle 0 Day 1 (C0D1) | Half-life of RXC004 following single dose on Cycle 0 Day1 when given in combination with Nivolumab. | PK parameter Half-life was analyzed at the indicated dose levels. | Posted | Median | Full Range | hours | Samples were analyzed from 0 - 48 hours after administration to evaluate PK parameters on Cycle 0 Day 1. |
|
|
|
| Secondary | Module 3 - PK Profile - AUC on Cycle 0 Day 1 (C0D1) | AUC was calculated from the measurement of mean plasma concentration of RXC004 at various time points from 0 - 48 hours following single dose of RXC004 | PK parameter AUC (0-24) was analyzed at the indicated dose level. | Posted | Mean | Standard Deviation | h*ng/ml | Samples were analyzed from 0 - 48 hours after administration to evaluate PK parameters on Cycle 0 Day 1. |
|
|
|
| Secondary | Module 3 - PK Profile - C24 on Cycle 0 Day 1 (C0D1) | Mean Plasma concentration of RXC004 at 24 h post-dose | PK parameter C24 was analyzed at the indicated dose level. | Posted | Mean | Standard Deviation | ng/ml | Samples were analyzed from 0 - 48 hours after administration to evaluate PK parameters on Cycle 0 Day 1. |
|
|
|
| Secondary | Module 3 - PK Profile - Cmax on Cycle 0 Day 1 (C0D1) | Maximum plasma concentration (Cmax) of RXC004 following single dose | PK parameter Cmax was analyzed at the indicated dose level. | Posted | Mean | Standard Deviation | ng/ml | Samples were analyzed from 0 - 48 hours after administration to evaluate PK parameters on Cycle 0 Day 1. |
|
|
|
| Secondary | Module 3 - PK Profile - Half-life on Cycle 0 Day 1 (C0D1) | Half-life of RXC004 following single dose. | Samples were analyzed from 0 - 48 hours after administration to evaluate PK parameters on Cycle 0 Day 1. | Posted | Median | Full Range | hours | Cycle 0 Day 1 |
|
|
|
| 0 |
| 4 |
| 0 |
| 4 |
| 0 |
| 4 |
| EG001 | Module 1 Arm 2 - Monotherapy RXC004 (1.0 mg) | Patients were given 1.0 mg RXC004 and monitored for Dose Limiting Toxicities. | 1 | 3 | 1 | 3 | 0 | 3 |
| EG002 | Module 1 Arm 3 - Monotherapy RXC004 (1.5 mg) | Patients were given 1.5 mg RXC004 and monitored for Dose Limiting Toxicities. | 3 | 7 | 5 | 7 | 0 | 7 |
| EG003 | Module 1 Arm 4 - Monotherapy RXC004 (2.0 mg) | Patients were given 2.0 mg RXC004 and monitored for Dose Limiting Toxicities. | 0 | 6 | 1 | 6 | 0 | 6 |
| EG004 | Module 1 Arm 5 - Monotherapy RXC004 (3.0 mg) | Patients were given 3.0 mg RXC004 and monitored for Dose Limiting Toxicities. | 1 | 4 | 3 | 4 | 0 | 4 |
| EG005 | Module 1 Arm 6 - Monotherapy RXC004 (10.0 mg) | Patients were given 10.0 mg RXC004 and monitored for Dose Limiting Toxicities. | 0 | 1 | 1 | 1 | 0 | 1 |
| EG006 | Module 2 Arm 1 - RXC004 (1.0 mg) Plus Nivolumab | Patients were given 1.0 mg RXC004 in combination with a standard dose of Nivolumab and monitored for Dose Limiting Toxicities. | 3 | 6 | 4 | 6 | 0 | 6 |
| EG007 | Module 2 Arm 2 - RXC004 (1.5 mg) Plus Nivolumab | Patients were given 1.5 mg RXC004 in combination with a standard dose of Nivolumab and monitored for Dose Limiting Toxicities. | 3 | 8 | 4 | 8 | 0 | 8 |
| EG008 | Intermittent Schedules of Monotherapy RXC004 - Module 3 | Patients were given RXC004 at 2 mg once a day (QD). Patients were treated for 2 weeks at the same dose, followed by 1 week off for 21 day treatment cycles. RXC004: RXC004 taken orally, inhibits porcupine (PORCN) and interacts with the wnt signaling pathway. | 1 | 7 | 4 | 7 | 0 | 7 |
| Sepsis | Infections and infestations | MedDRA 24.1 | Systematic Assessment |
|
| Device related sepsis | Infections and infestations | MedDRA 24.1 | Systematic Assessment |
|
| Lower respiratory infection | Infections and infestations | MedDRA 24.1 | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA 24.1 | Systematic Assessment |
|
| Colitis | Gastrointestinal disorders | MedDRA 24.1 | Systematic Assessment |
|
| Enteritis | Gastrointestinal disorders | MedDRA 24.1 | Systematic Assessment |
|
| Small intestinal obstruction | Gastrointestinal disorders | MedDRA 24.1 | Systematic Assessment |
|
| Biliary tract infection | Infections and infestations | MedDRA 24.1 | Systematic Assessment |
|
| COVID-19 | Infections and infestations | MedDRA 24.1 | Systematic Assessment |
|
| Escherichia Urinary tract infection | Infections and infestations | MedDRA 24.1 | Systematic Assessment |
|
| Gastroenteritis viral | Infections and infestations | MedDRA 24.1 | Systematic Assessment |
|
| Stoma site infection | Infections and infestations | MedDRA 24.1 | Systematic Assessment |
|
| Atrial fibrillation | Cardiac disorders | MedDRA 24.1 | Systematic Assessment |
|
| Ascites | Gastrointestinal disorders | MedDRA 24.1 | Systematic Assessment |
|
| Drug-induced liver injury | Hepatobiliary disorders | MedDRA 24.1 | Systematic Assessment |
|
| Hepatic pain | Hepatobiliary disorders | MedDRA 24.1 | Systematic Assessment |
|
| Diverticulitis | Infections and infestations | MedDRA 24.1 | Systematic Assessment |
|
| Kidney infection | Infections and infestations | MedDRA 24.1 | Systematic Assessment |
|
| Muscular weakness | Musculoskeletal and connective tissue disorders | MedDRA 24.1 | Systematic Assessment |
|
| Humerus fracture | Injury, poisoning and procedural complications | MedDRA 24.1 | Systematic Assessment |
|
| Subdural haematoma | Injury, poisoning and procedural complications | MedDRA 24.1 | Systematic Assessment |
|
| Colorectal cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 24.1 | Systematic Assessment |
|
| Pulmonary haemorrhage | Respiratory, thoracic and mediastinal disorders | MedDRA 24.1 | Systematic Assessment |
|
| Urosepsis | Infections and infestations | MedDRA 24.1 | Systematic Assessment |
|
| Infection | Infections and infestations | MedDRA 24.1 | Systematic Assessment |
|
Not provided
Not provided
| D013899 | Thoracic Neoplasms |
| D008206 | Lymphatic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D007162 |
| Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |