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

NCT ID: NCT04907851

Last Updated: 2025-03-17

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

45 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-12-10

Study Completion Date

2023-11-30

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Advanced Solid Tumours

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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

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.

Group Type EXPERIMENTAL

RXC004

Intervention Type DRUG

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

Denosumab

Intervention Type BIOLOGICAL

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

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

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.

Group Type EXPERIMENTAL

RXC004

Intervention Type DRUG

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.

Denosumab

Intervention Type BIOLOGICAL

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

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

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.

Group Type EXPERIMENTAL

RXC004

Intervention Type DRUG

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

Denosumab

Intervention Type BIOLOGICAL

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

pembrolizumab

Intervention Type BIOLOGICAL

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

Interventions

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RXC004

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

Intervention Type DRUG

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.

Intervention Type DRUG

RXC004

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

Intervention Type DRUG

Denosumab

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

Intervention Type BIOLOGICAL

pembrolizumab

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

Intervention Type BIOLOGICAL

Other Intervention Names

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zamaporvint zamaporvint zamaporvint KEYTRUDA®

Eligibility Criteria

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Inclusion Criteria

* 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.

Exclusion Criteria

* Prior therapy with a compound of the same mechanism of action as RXC004
* Patients at higher risk of bone fractures
* Any known uncontrolled inter-current illness or persistent clinically significant toxicity related to prior anti-cancer treatment
* Patients who have any history of an active (requiring treatment) other malignancy within 2 years of study entry
* Patients with known or suspected brain metastases
* Use of anti-neoplastic agents
* 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
* Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior the first dose of pembrolizumab in this study
* Has severe hypersensitivity (≥ Grade 3) to pembrolizumab and/or any of its excipients
* Has an active autoimmune disease that has required systemic treatment in past 2 years
* Has a history of (non-infectious) pneumonitis / interstitial lung disease that required steroids or has current pneumonitis / interstitial lung disease
* Has an active infection requiring systemic therapy
* Patients with a history of allogeneic tissue/solid organ transplant
* Patients with active infections, including tuberculosis, HIV, HBV, or HCV
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role collaborator

Redx Pharma Ltd

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Wollongong Hospital

Wollongong, New South Wales, Australia

Site Status

The Alfred Hospital - Alfred Health

Melbourne, Victoria, Australia

Site Status

Cambridge University Hospital NHS Foundation Trust

Cambridge, , United Kingdom

Site Status

Beatson West of Scotland Cancer Care

Glasgow, , United Kingdom

Site Status

St James University Hospital

Leeds, , United Kingdom

Site Status

Barts Cancer Institute - Haemato-Oncology

London, , United Kingdom

Site Status

University College Hospitals NHS Foundation Trust

London, , United Kingdom

Site Status

Royal Free London Foundation NHS Trust

London, , United Kingdom

Site Status

Imperial College Healthcare NHS Trust - Hammersmith Hospital

London, , United Kingdom

Site Status

The Christie NHS Foundation Trust - Medical Oncology

Manchester, , United Kingdom

Site Status

Oxford Cancer and Haematology Centre Churchill Hospital

Oxford, , United Kingdom

Site Status

Weston Park Hospital

Sheffield, , United Kingdom

Site Status

The Royal Marsden Hospital (Surrey)

Sutton, , United Kingdom

Site Status

Countries

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Australia United Kingdom

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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MK-3475-E86

Identifier Type: OTHER

Identifier Source: secondary_id

KEYNOTE-E86

Identifier Type: OTHER

Identifier Source: secondary_id

2020-005804-20

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

RXC004/0003

Identifier Type: -

Identifier Source: org_study_id

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