Neoplasms

All Conditions

Digestive System Diseases

Gland and Hormone Related Diseases

Symptoms and General Pathology

Rare Diseases

Cholangiocarcinoma

Adenocarcinoma

Pancreatic Neoplasms

Disease Progression

Pancreatic Cancer

Bile Duct Cancer

Biliary Tract Cancer

Antineoplastic Agents

All Drugs and Chemicals

Bone Density Conservation Agents

Pembrolizumab

Denosumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Patients (Karnofsky performance status ≥70) will be recruited and dosed with RXC004 (2 mg once daily \[QD\], orally) within 6 weeks of progression following 1st line SoC treatment.

Patients (Eastern Cooperative Oncology Group \[ECOG\] performance status 0-1) will be recruited and dosed with RXC004 within 6 weeks of progression, following 1st line SoC treatment.

Patients (ECOG performance status 0-1) will be recruited and dosed with RXC004 (1.5 mg QD, orally) in combination with pembrolizumab 400 mg IV infusion every 6 weeks (q6w) within 6 weeks of progression, following 1st line Soc treatment.

RXC004 will be administered orally, 2 mg QD; Dose Formulation: 0.5 mg or 1 mg capsules.

RXC004

RXC004 will be administered orally, 2 mg QD (Cohort 1, Module 2) and 1 mg QD (Cohort 2, Module 2); Dose Formulation: 0.5 mg or 1 mg capsules.

RXC004 will be administered orally, 1.5 mg QD; Dose Formulation: 0.5 mg or 1 mg capsules.

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

Pembrolizumab will be administered via intravenous infusion, 400 mg dose once every 6 weeks

pembrolizumab

This study is to evaluate the preliminary efficacy and safety of RXC004 monotherapy and in combination with pembrolizumab in advanced solid tumours that have progressed following SoC treatment.

This Phase II, modular, open label, multicentre study initially opened with ring finger protein 43 (RNF43) loss of function (LoF) mutation-positive pancreatic ductal adenocarcinoma (PDAC) (Module 1) and molecularly unselected biliary tract cancer (BTC) (Module 2) modules. Module 3 will investigate RXC004 in combination with pembrolizumab in BTC. Modules 1 and 2 are monotherapies and Module 3 is the combination therapy.

The primary objective of the study is to assess the preliminary efficacy of RXC004 in each module. This will be evaluated in terms of progression free survival (PFS) at 6 months in Modules 1 and 2, and in terms of Objective response rate (ORR) in Module 3. Following radiological progression, patients will be followed-up for survival.

A Study to Assess RXC004 Efficacy in Advanced Solid Tumours After Progression on Standard of Care (SoC) Therapy (PORCUPINE2)

A Modular, Phase II, Open-Label, Multicentre Study to Assess the Preliminary Efficacy and Safety of RXC004, in Patients With Advanced Solid Tumours That Have Progressed Following Therapy With Current Standard of Care

To assess the anti-tumour activity of RXC004. Progression free survival rate at 6 months is defined as the proportion of patients who remain alive and free of progression at 6 months.

To assess the anti-tumour activity of RXC004 as combination therapy. ORR, defined as the proportion of patients with a best overall response of complete response or partial response, based on local investigator assessment, as defined in RECIST 1.1.

To further assess the preliminary efficacy of RXC004. ORR is defined as the proportion of patients with a best overall response of complete response (CR) or partial response (PR), based on local Investigator assessment, as defined in RECIST 1.1.

To further assess the preliminary efficacy of RXC004 as monotherapy and as combination therapy. DCR is defined as the proportion of patients with a best overall response of either CR, PR or stable disease (SD) for at least 6 weeks.

To further assess the preliminary efficacy of RXC004 as monotherapy and as combination therapy. 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), regardless whether the patient withdraws from the assigned study treatment or receives another anticancer prior to progression.

To further assess the preliminary efficacy of RXC004 as monotherapy and as combination therapy. 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.

To further assess the preliminary efficacy of RXC004 as monotherapy and as combination therapy. OS is defined as the time from first day of study treatment until death due to any cause.

To assess the pharmacokinetic (PK) of RXC004 as monotherapy and as combination therapy.

To assess the PK of RXC004 as monotherapy and as combination therapy.

To assess the safety and tolerability profile of RXC004 as monotherapy and as combination therapy.

Merck Sharp & Dohme LLC

Redx Pharma Plc

Nivolumab

Antibodies

Antibodies, Monoclonal

Immunoglobulins

Immunoglobulin G

Immunoglobulins, Intravenous

Myeloma Proteins

Paraproteins

Patients will be given RXC004 at a specified dose level and reviewed for Dose Limiting Toxicities. Once the DLT period is complete RXC004 will be given at a higher dose until MTD is reached.

Patients will be given RXC004 at specific doses in combination with a standard dose of Nivolumab and reviewed for Dose Limiting Toxicities. Once the DLT period is complete, RXC004 will be given at a higher dose until MTD is reached.

Patients will be given RXC004 at specific doses. One group will be treated for 4 days, followed by 3 days off; repeated weekly for 21 days. A second group will be treated for 2 weeks at the same dose, followed by 1 week off for 21 days.

RXC004 is taken orally, inhibits porcupine (PORCN) and interacts with the wnt signalling pathway.

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

Natalie Cook

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.

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.

Study to Evaluate the Safety and Tolerability of RXC004 in Advanced Malignancies

A Modular Multi-Arm, Phase 1, Adaptive Design Study to Evaluate the Safety and Tolerability of RXC004, Alone and in Combination With Anti-cancer Treatments, in Patients With Advanced Malignancies

A DLT is defined as an adverse event or abnormal laboratory value. Haematological toxicity of CTCAE grade 4 for more than 4 consecutive days. Grade 3 neutropenia of any duration accompanied by fever \>38.5 degrees Celsius. Grage 3 thrombocytopaenia with bleeding. Any other confirmed haematological toxicity \>CTCAE grade 4. Non-haematological toxicity \>CTCAE grade 3. Any other toxicity that is judged to be a DLT by the Safety Review Committee. An AE resulting in disrupted dosing \>14 days.

A DLT is defined as an adverse event or abnormal laboratory value. Haematological toxicity of CTCAE grade 4 for more than 4 consecutive days. Grade 3 neutropenia of any duration accompanied by fever \>38.5 degrees Celsius. Grage 3 thrombocytopaenia with bleeding. Any other confirmed haematological toxicity \>CTCAE grade 4. Non-haematological toxicity \>CTCAE grade 3. 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

A DLT is defined as an adverse event or abnormal laboratory value. Haematological toxicity of CTCAE grade 4 present for more than 4 consecutive days.

Grade 3 neutropenia of any duration accompanied by fever \>38.5 degrees Celsius. Grade 3 thrombocytopaenia with bleeding. Any other confirmed haematological toxicity CTCAE \>grade 4. Non-haematological toxicity CTCAE \>grade 3. 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.

Characterise the PK profile of RXC004 following single dose and at steady state and after multiple dose.

Characterise the PK profile of RXC004 in combination with Nivolumab to following single dose and at steady state and after multiple dose.

Characterise the PK profile of RXC004 following intermittent dosing schedule.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study to Assess RXC004 Efficacy in Advanced Solid Tumours After Progression on Standard of Care (SoC) Therapy (PORCUPINE2)	NCT04907851	Advanced Solid ...	RXC004 RXC004 RXC004 Denosumab pembrolizumab	18 Years -	Redx Pharma Plc
Study to Evaluate the Safety and Tolerability of RXC004 in Advanced Malignancies	NCT03447470	Cancer Solid Tumor	RXC004 Nivolumab	18 Years -	Redx Pharma Plc
Study to Evaluate the Safety and Tolerability of RXC004 in Advanced Malignancies	NCT03447470	Cancer Solid Tumor	RXC004 Nivolumab	18 Years -	Redx Pharma Plc

Spots Global Cancer Trial Database for rxc004

Every month we try and update this database with for rxc004 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for rxc004

Every month we try and update this database with for rxc004 cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for rxc004 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.