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

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