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

NCT04907851 | Completed Phase 2 Results

• 4 other identifiers: RXC004/0003MK-3475-E86KEYNOTE-E862020-005804-20
• Study Type: interventional
• Target: 45
• Locations: 2 countries
• Sites: 13

Brief Summary

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.

Conditions

Advanced Solid Tumours

Keywords

Open-Label; RXC004; Ring finger protein 43; Pancreatic ductal adenocarcinoma; Biliary tract cancer; Efficacy; Safety; Pharmacokinetics; Pancreatic cancer; Cholangiocarcinoma; Gallbladder; Ampullary Cancer; Ampulla of Vater; MK-3475-E86; zamaporvint

Outcome Measures

Primary Outcomes (2)

• Monotherapy (Modules 1 and 2): Progression Free Survival Rate at 6 Months

  The anti-tumour activity of RXC004 was assessed. Progression free survival rate at 6 months was defined as the percentage of patients who remained alive and free of progression at 6 months according to Kaplan-Meier estimates.

  At 6 months

• Combination Therapy (Module 3): Objective Response Rate (ORR)

  The anti-tumour activity of RXC004 as a combination therapy was assessed. ORR was defined as the percentage of patients with a best overall response of complete response or partial response based on local investigator assessment as defined in RECIST 1.1.

  Up to 23 months

Secondary Outcomes (14)

• Monotherapy (Modules 1 and 2): ORR

  Up to 23 months

• Monotherapy (Modules 1 and 2) and Combination Therapy (Module 3): Disease Control Rate (DCR)

  Up to 23 months

• Monotherapy (Modules 1 and 2) and Combination Therapy (Module 3): PFS

  Up to 23 months

• Monotherapy (Modules 1 and 2) and Combination Therapy (Module 3): Best Percentage Change in Tumor Size

  Up to 23 months

• Monotherapy (Modules 1 and 2) and Combination Therapy (Module 3): Overall Survival (OS)

  Up to 23 months

Study Arms (3)

Module 1 - RNF43 Mutated Advanced (unresectable)/Metastatic Pancreatic Cancer (Stage III/IV)

EXPERIMENTAL

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.

Drug: RXC004; Biological: Denosumab

Module 2 -Advanced (unresectable)/Metastatic Biliary Tract Cancer (Stage III/IV)

EXPERIMENTAL

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.

Drug: RXC004; Biological: Denosumab

Module 3-Advanced (unresectable)/Metastatic Biliary Tract Cancer (Stage Ill/IV) Combination Therapy

EXPERIMENTAL

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.

Drug: RXC004; Biological: Denosumab; Biological: pembrolizumab

Interventions

RXC004 DRUG

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

Also known as: zamaporvint

Module 1 - RNF43 Mutated Advanced (unresectable)/Metastatic Pancreatic Cancer (Stage III/IV)

Denosumab BIOLOGICAL

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

Module 1 - RNF43 Mutated Advanced (unresectable)/Metastatic Pancreatic Cancer (Stage III/IV); Module 2 -Advanced (unresectable)/Metastatic Biliary Tract Cancer (Stage III/IV); Module 3-Advanced (unresectable)/Metastatic Biliary Tract Cancer (Stage Ill/IV) Combination Therapy

pembrolizumab BIOLOGICAL

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

Also known as: KEYTRUDA®

Module 3-Advanced (unresectable)/Metastatic Biliary Tract Cancer (Stage Ill/IV) Combination Therapy

Eligibility Criteria

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

You may qualify if:

• At least one lesion that is measurable by RECIST 1.1 at baseline (within 6 weeks prior to start of study treatment).
• Mandatory paired biopsies; Patients must have at least one lesion suitable for biopsy at screening
• Adequate organ and marrow function
• 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 from the time of treatment initiation, and for at least 5 months after the last dose of study drug.
• Histological documentation of advanced (unresectable)/metastatic (Stage III/IV) PDAC, with documented loss of function tumour mutation in RNF43
• Patients must have received one prior systemic treatment for advanced (unresectable)/metastatic PDAC (Stage III/IV), with clear evidence of radiological disease progression
• Patients must be enrolled and receive first dose of study treatment within 6 weeks of radiologically confirmed progression
• Karnofsky performance status ≥70.
• Histological documentation of advanced (unresectable)/metastatic (Stage III/IV) BTC (intrahepatic or extrahepatic cholangiocarcinoma, ampulla of Vater, or gallbladder cancer)
• Patients must have received one prior systemic treatment for advanced (unresectable)/metastatic BTC, with clear evidence of radiological disease progression
• Patients must be enrolled and receive first dose of study treatment within 6 weeks of radiologically confirmed progression
• ECOG status 0 or 1.

You may not qualify if:

• Prior therapy with a compound of the same mechanism of action as RXC004
• Patients at higher risk of bone fractures
• Any known uncontrolled inter-current illness or persistent clinically significant toxicity related to prior anti-cancer treatment
• Patients who have any history of an active (requiring treatment) other malignancy within 2 years of study entry
• Patients with known or suspected brain metastases
• Use of anti-neoplastic agents
• Patients with a known hypersensitivity to any RXC004 excipients
• Patients with a contra-indication for denosumab treatment
• Patients who are pregnant or breast-feeding
• Known active human immunodeficiency viruses (HIV), hepatitis B (HBV), or hepatitis C (HCV) infections
• Use of any live or live-attenuated vaccines against infectious diseases (e.g., influenza nasal spray, varicella) within 4 weeks (28 days) of initiation of study treatment
• Mean resting corrected QTcF \>470 ms, obtained from triplicate ECGs performed at screening.
• Patients with any contraindication to the use of pembrolizumab as per approved label
• Has received prior therapy with an anti-programmed cell death-1 (anti-PD-1), anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor, and was discontinued from that treatment due to a Grade 3 or higher AE
• Has received prior radiotherapy within 2 weeks of start of study treatment or have had a history of radiation pneumonitis

Sponsors & Collaborators

• Redx Pharma Ltd: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (13)

Wollongong Hospital

Wollongong, New South Wales, 2500, Australia

Location

The Alfred Hospital - Alfred Health

Melbourne, Victoria, 3304, Australia

Location

Cambridge University Hospital NHS Foundation Trust

Cambridge, CB2 0XY, United Kingdom

Location

Beatson West of Scotland Cancer Care

Glasgow, G12 0YN, United Kingdom

Location

St James University Hospital

Leeds, LS9 7TF, United Kingdom

Location

Barts Cancer Institute - Haemato-Oncology

London, EC1M 6BQ, United Kingdom

Location

University College Hospitals NHS Foundation Trust

London, NW1 2BU, United Kingdom

Location

Royal Free London Foundation NHS Trust

London, NW3 2QG, United Kingdom

Location

Imperial College Healthcare NHS Trust - Hammersmith Hospital

London, W12 0HS, United Kingdom

Location

The Christie NHS Foundation Trust - Medical Oncology

Manchester, M20 4BX, United Kingdom

Location

Oxford Cancer and Haematology Centre Churchill Hospital

Oxford, OX3 7LE, United Kingdom

Location

Weston Park Hospital

Sheffield, S10 2SJ, United Kingdom

Location

The Royal Marsden Hospital (Surrey)

Sutton, SM25PT, United Kingdom

Location

MeSH Terms

Conditions

Biliary Tract Neoplasms; Pancreatic Neoplasms; Cholangiocarcinoma

Interventions

Denosumab; pembrolizumab

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Biliary Tract Diseases; Digestive System Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Endocrine System Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Craig Tilston
• Organization: Redx Pharma Limited

c.tilston@redxpharma.com

+44 (0)7787 983 638

Publication Agreements

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

Study Design

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

Study Record Dates

• First Submitted: May 25, 2021
• First Posted: June 1, 2021
• Study Start: December 10, 2021
• Primary Completion: November 30, 2023
• Study Completion: November 30, 2023
• Last Updated: March 17, 2025
• Results First Posted: March 17, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

AU (2); GB (11)