A Study to Assess RXC004 Efficacy in Advanced Solid Tumours After Progression on Standard of Care (SoC) Therapy (PORCUPINE2) (KEYNOTE-E86)

Redx Pharma Ltd

Status and phase

Completed

Phase 2

Conditions

Advanced Solid Tumours

Treatments

Biological: Denosumab

Biological: pembrolizumab

Drug: RXC004

Study type

Interventional

Funder types

Industry

Identifiers

NCT04907851

MK-3475-E86 (Other Identifier)

KEYNOTE-E86 (Other Identifier)

RXC004/0003

2020-005804-20 (EudraCT Number)

Details and patient eligibility

About

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.

Full description

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.

Enrollment

45 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

Core 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.

Module 1 (PDAC) Specific Inclusion Criteria

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.

Module 2 and Module 3 (BTC) Specific Inclusion Criteria

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.

Core 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.

There are no exclusion criteria specific to Modules 1 and 2.

Module 3 Specific Exclusion Criteria:

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

Trial design

Primary purpose

Treatment

Allocation

Non-Randomized

Interventional model

Parallel Assignment

Masking

None (Open label)

45 participants in 3 patient groups

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

Experimental group

Description:

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.

Treatment:

Drug: RXC004

Biological: Denosumab

Drug: RXC004

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

Experimental group

Description:

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.

Treatment:

Drug: RXC004

Biological: Denosumab

Drug: RXC004

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

Experimental group

Description:

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.

Treatment:

Drug: RXC004

Biological: pembrolizumab

Drug: RXC004

Biological: Denosumab

Drug: RXC004

Trial documents