Core Inclusion Criteria:  At least one lesion that is measurable by RECIST 1.1 at baseline (within 28 days 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 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 RECIST1.1 progression Karnofsky performance status ≥70.  Module 2 (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 RECIST1.1 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 and other investigational drugs within 4 weeks prior to the first dose of study treatment 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 vaccines against infectious diseases (e.g., influenza, varicella) within 4 weeks (28 days) of initiation of study treatment.