PORCUPINE2: This Phase II study is evaluating the effectiveness of a new targeted therapy (RXC004) in people with RNF43 mutation advanced or metastatic pancreatic ductal cancer or biliary tract cancer that have progressed following standard of care treatmentA 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

Exclusion

• 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