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

Criteria the registry did not label

• 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