A Study to Assess RXC004 Efficacy in Advanced Solid Tumou... | NCT04907851

NCT04907851

ID	Type	Description
MK-3475-E86	Other Identifier	Collaboration requirements
KEYNOTE-E86	Other Identifier	Collaboration requirements
2020-005804-20	EudraCT Number

Status Module

Sponsor/Collaborators Module

Name	Class
Merck Sharp & Dohme LLC	INDUSTRY

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Module 1 - RNF43 Mutated Advanced (unresectable)/Metastatic Pancreatic Cancer (Stage III/IV)	Experimental	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.	Drug: RXC004 Biological: Denosumab
Module 2 -Advanced (unresectable)/Metastatic Biliary Tract Cancer (Stage III/IV)	Experimental	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.	Drug: RXC004 Biological: Denosumab
Module 3-Advanced (unresectable)/Metastatic Biliary Tract Cancer (Stage Ill/IV) Combination Therapy	Experimental	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.	Drug: RXC004 Biological: Denosumab Biological: pembrolizumab

Interventions

Name	Type	Description	Arm Group Labels	Other Names
RXC004	Drug	RXC004 will be administered orally, 2 mg QD; Dose Formulation: 0.5 mg or 1 mg capsules.	Module 1 - RNF43 Mutated Advanced (unresectable)/Metastatic Pancreatic Cancer (Stage III/IV)

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Monotherapy (Modules 1 and 2): Progression Free Survival Rate at 6 Months	The anti-tumour activity of RXC004 was assessed. Progression free survival rate at 6 months was defined as the percentage of patients who remained alive and free of progression at 6 months according to Kaplan-Meier estimates.	At 6 months
Combination Therapy (Module 3): Objective Response Rate (ORR)	The anti-tumour activity of RXC004 as a combination therapy was assessed. ORR was defined as the percentage of patients with a best overall response of complete response or partial response based on local investigator assessment as defined in RECIST 1.1.	Up to 23 months

Secondary Outcomes

Measure	Description	Time Frame
Monotherapy (Modules 1 and 2): ORR	The preliminary efficacy of RXC004 was assessed. ORR was defined as the percentage of patients with a best overall response of complete response (CR) or partial response (PR) based on local Investigator assessment as defined in RECIST 1.1.	Up to 23 months
Monotherapy (Modules 1 and 2) and Combination Therapy (Module 3): Disease Control Rate (DCR)

Eligibility Module

Eligibility 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

Contacts/Locations Module

Facility	Status	City	State	ZIP	Country	Contacts
Wollongong Hospital		Wollongong	New South Wales	2500	Australia
The Alfred Hospital - Alfred Health

References Module

No data available

No data is available for this block.

IPD Sharing Statement Module

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Module 1-RNF43 Mutated Advanced (Unresectable)/Metastatic Pancreatic Cancer (Stage III/IV)	Patients (Karnofsky performance status ≥70) were recruited and dosed with RXC004 (2 mg once daily [QD] orally) within 6 weeks of progression following 1st line Standard of Care (SoC) treatment.
FG001

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Jan 4, 2023	Nov 7, 2024

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

Intervention Browse Module

Masking Info

Full analysis set included all patients who were enrolled and received at least one dose of RXC004 in Modules 1 and 2, and at least one dose of RXC004 or pembrolizumab in Module 3.

Arm/Group Information

ID	Title	Description
BG000	Module 1-RNF43 Mutated Advanced (Unresectable)/Metastatic Pancreatic Cancer (Stage III/IV)	Patients (Karnofsky performance status ≥70) were recruited and dosed with RXC004 (2 mg QD orally) within 6 weeks of progression following 1st line SoC treatment.
BG001	Module 2-Advanced (Unresectable)/Metastatic Biliary Tract Cancer (Stage III/IV)	Patients (ECOG performance status 0-1) were recruited and dosed with RXC004 within 6 weeks of progression following 1st line SoC treatment.
BG002	Module 3-Advanced (Unresectable)/Metastatic Biliary Tract Cancer (Stage Ill/IV) Combination Therapy	Patients (ECOG performance status 0-1) were 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.
BG003	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00065.7± 7.94 BG00155.8± 14.72 BG00258.1± 10.85 BG003

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG0003 BG00110 BG002

Race/Ethnicity, Customized

Count of Participants

Participants

Title

Denominators

Categories

Asian

Title	Measurements
	BG0002 BG0010 BG002

Race/Ethnicity, Customized

Count of Participants

Participants

Title

Denominators

Categories

Not Hispanic or Latino

Title	Measurements
	BG0005 BG00117 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Monotherapy (Modules 1 and 2): Progression Free Survival Rate at 6 Months

The anti-tumour activity of RXC004 was assessed. Progression free survival rate at 6 months was defined as the percentage of patients who remained alive and free of progression at 6 months according to Kaplan-Meier estimates.

Full analysis set included all patients who were enrolled and received at least one dose of RXC004 in Modules 1 and 2, and at least one dose of RXC004 or pembrolizumab in Module 3.

Posted

Number

90% Confidence Interval

percentage of participants

At 6 months

ID	Title	Description
OG000	Module 1-RNF43 Mutated Advanced (Unresectable)/Metastatic Pancreatic Cancer (Stage III/IV)	Patients (Karnofsky performance status ≥70) were recruited and dosed with RXC004 (2 mg QD orally) within 6 weeks of progression following 1st line SoC treatment.
OG001	Module 2-Advanced (Unresectable)/Metastatic Biliary Tract Cancer (Stage III/IV)	Patients (ECOG performance status 0-1) were recruited and dosed with RXC004 within 6 weeks of progression following 1st line SoC treatment.

Units	Counts
Participants	OG0006 OG00120

Title

Denominators

Categories

Title	Measurements
	OG000NA(NA to NA)The estimate of PFS at 6-months could not be calculated as the final surviving patient withdrew consent and was censored at 2.73 months. The Kaplan-Meier survival curve, from which the estimates would have been derived, did not extend to 6-months. OG0016.1(0.73 to 20.53)

Primary

Combination Therapy (Module 3): Objective Response Rate (ORR)

The anti-tumour activity of RXC004 as a combination therapy was assessed. ORR was defined as the percentage of patients with a best overall response of complete response or partial response based on local investigator assessment as defined in RECIST 1.1.

Full analysis set included all patients who were enrolled and received at least one dose of RXC004 in Modules 1 and 2, and at least one dose of RXC004 or pembrolizumab in Module 3.

Posted

Number

90% Confidence Interval

percentage of participants

Up to 23 months

ID	Title	Description
OG000	Module 3-Advanced (Unresectable)/Metastatic Biliary Tract Cancer (Stage Ill/IV) Combination Therapy	Patients (ECOG performance status 0-1) were recruited and dosed with RXC004 (1.5 mg QD orally) in combination with pembrolizumab 400 mg IV infusion q6w within 6 weeks of progression following 1st line SoC treatment.

Units	Counts
Participants	OG000

Secondary

Monotherapy (Modules 1 and 2): ORR

The preliminary efficacy of RXC004 was assessed. ORR was defined as the percentage of patients with a best overall response of complete response (CR) or partial response (PR) based on local Investigator assessment as defined in RECIST 1.1.

Full analysis set included all patients who were enrolled and received at least one dose of RXC004 in Modules 1 and 2, and at least one dose of RXC004 or pembrolizumab in Module 3.

Posted

Number

90% Confidence Interval

percentage of participants

Up to 23 months

ID	Title	Description
OG000	Module 1-RNF43 Mutated Advanced (Unresectable)/Metastatic Pancreatic Cancer (Stage III/IV)	Patients (Karnofsky performance status ≥70) were recruited and dosed with RXC004 (2 mg QD orally) within 6 weeks of progression following 1st line SoC treatment.
OG001	Module 2-Advanced (Unresectable)/Metastatic Biliary Tract Cancer (Stage III/IV)	Patients (ECOG performance status 0-1) were recruited and dosed with RXC004 within 6 weeks of progression following 1st line SoC treatment.

Units	Counts
Participants

Secondary

Monotherapy (Modules 1 and 2) and Combination Therapy (Module 3): Disease Control Rate (DCR)

The preliminary efficacy of RXC004 as a monotherapy and as a combination therapy was assessed. DCR was defined as the percentage of patients with a best overall response of either CR, PR or stable disease (SD) for at least 6 weeks.

Full analysis set included all patients who were enrolled and received at least one dose of RXC004 in Modules 1 and 2, and at least one dose of RXC004 or pembrolizumab in Module 3.

Posted

Number

90% Confidence Interval

percentage of participants

Up to 23 months

ID	Title	Description
OG000	Module 1-RNF43 Mutated Advanced (Unresectable)/Metastatic Pancreatic Cancer (Stage III/IV)	Patients (Karnofsky performance status≥70) were recruited and dosed with RXC004 (2 mg QD orally) within 6 weeks of progression following 1st line SoC treatment.
OG001	Module 2-Advanced (Unresectable)/Metastatic Biliary Tract Cancer (Stage III/IV)	Patients (ECOG performance status 0-1) were recruited and dosed with RXC004 within 6 weeks of progression following 1st line SoC treatment.
OG002	Module 3-Advanced (Unresectable)/Metastatic Biliary Tract Cancer (Stage Ill/IV) Combination Therapy

Secondary

Monotherapy (Modules 1 and 2) and Combination Therapy (Module 3): PFS

The preliminary efficacy of RXC004 as a monotherapy and as a combination therapy was assessed. PFS was defined as the time from first dose of study treatment until the date of disease progression or death (by any cause in the absence of progression) regardless whether the patient withdrew from the assigned study treatment or received another anticancer prior to progression.

Full analysis set included all patients who were enrolled and received at least one dose of RXC004 in Modules 1 and 2, and at least one dose of RXC004 or pembrolizumab in Module 3.

Posted

Median

95% Confidence Interval

months

Up to 23 months

ID	Title	Description
OG000	Module 1-RNF43 Mutated Advanced (Unresectable)/Metastatic Pancreatic Cancer (Stage III/IV)	Patients (Karnofsky performance status≥70) were recruited and dosed with RXC004 (2 mg QD orally) within 6 weeks of progression following 1st line SoC treatment.
OG001	Module 2-Advanced (Unresectable)/Metastatic Biliary Tract Cancer (Stage III/IV)	Patients (ECOG performance status 0-1) were recruited and dosed with RXC004 within 6 weeks of progression following1st line SoC treatment.
OG002	Module 3-Advanced (Unresectable)/Metastatic Biliary Tract Cancer (Stage Ill/IV) Combination Therapy

Secondary

Monotherapy (Modules 1 and 2) and Combination Therapy (Module 3): Best Percentage Change in Tumor Size

The preliminary efficacy of RXC004 as a monotherapy and as a combination therapy was assessed. The best percentage change in tumour size was determined at a patient level. For each patient, it represents the largest decrease (or smallest increase) in tumour size. Percentage change in tumour size was derived at each visit by the percentage change from baseline in the sum of diameters of all target lesions.

Full analysis set included all patients who were enrolled and received at least one dose of RXC004 in Modules 1 and 2, and at least one dose of RXC004 or pembrolizumab in Module 3.

Posted

Median

Full Range

Percentage change in tumour size

Up to 23 months

ID	Title	Description
OG000	Module 1-RNF43 Mutated Advanced (Unresectable)/Metastatic Pancreatic Cancer (Stage III/IV)	Patients (Karnofsky performance status≥70) were recruited and dosed with RXC004 (2 mg QD orally) within 6 weeks of progression following 1st line SoC treatment.
OG001	Module 2-Advanced (Unresectable)/Metastatic Biliary Tract Cancer (Stage III/IV)	Patients (ECOG performance status 0-1) were recruited and dosed with RXC004 within 6 weeks of progression following 1st line SoC treatment.
OG002	Module 3-Advanced (Unresectable)/Metastatic Biliary Tract Cancer (Stage Ill/IV) Combination Therapy

Secondary

Monotherapy (Modules 1 and 2) and Combination Therapy (Module 3): Overall Survival (OS)

The preliminary efficacy of RXC004 as a monotherapy and as a combination therapy was assessed. OS was defined as the time from first day of study treatment until death due to any cause.

Full Analysis Set included all patients who enrolled and received at least one dose of RXC004 in Modules 1 and 2, and at least one dose of RXC004 or pembrolizumab in Module 3.

Posted

Median

95% Confidence Interval

Months

Up to 23 months

ID	Title	Description
OG000	Module 1-RNF43 Mutated Advanced (Unresectable)/Metastatic Pancreatic Cancer (Stage III/IV)	Patients (Karnofsky performance status ≥70) were recruited and dosed with RXC004 (2 mg QD orally) within 6 weeks of progression following 1st line SoC treatment.
OG001	Module 2-Advanced (Unresectable)/Metastatic Biliary Tract Cancer (Stage III/IV)	Patients (ECOG performance status 0-1) were recruited and dosed with RXC004 within 6 weeks of progression following 1st line SoC treatment
OG002	Module 3-Advanced (Unresectable)/Metastatic Biliary Tract Cancer (Stage Ill/IV) Combination Therapy	Patients (ECOG performance status 0-1) were 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.

Secondary

Maximum Observed Plasma Concentration (Cmax)

The pharmacokinetics (PK) of RXC004 as a monotherapy and as a combination therapy was assessed.

PK Analysis Set included all patients in the safety analysis set who have had at least one blood sample.

Posted

Geometric Mean

Geometric Coefficient of Variation

nanogram per milliliter (ng/mL)

At Cycle 0 Day 1 and Cycle 1 Day 15 (Each cycle was 21 days in length)

ID	Title	Description
OG000	Module 1-RNF43 Mutated Advanced (Unresectable)/Metastatic Pancreatic Cancer (Stage III/IV)	Patients (Karnofsky performance status ≥70) were recruited and dosed with RXC004 (2 mg once daily [QD] orally) within 6 weeks of progression following 1st line Standard of Care (SoC) treatment.
OG001	Module 2-Advanced (Unresectable)/Metastatic Biliary Tract Cancer (Stage III/IV)	Patients (Eastern Cooperative Oncology Group [ECOG] performance status 0-1) were recruited and dosed with RXC004 within 6 weeks of progression following 1st line SoC treatment.
OG002	Module 3-Advanced (Unresectable)/Metastatic Biliary Tract Cancer (Stage Ill/IV) Combination Therapy	Patients (ECOG performance status 0-1) were 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.

Secondary

Time to Cmax (Tmax)

The PK (tmax) of RXC004 as a monotherapy and as a combination therapy was assessed.

PK Analysis Set included all patients in the safety analysis set who have had at least one blood sample.

Posted

Geometric Mean

Geometric Coefficient of Variation

hour (h)

At Cycle 0 Day 1 and Cycle 1 Day 15 (Each cycle was 21 days in length)

ID	Title	Description
OG000	Module 1-RNF43 Mutated Advanced (Unresectable)/Metastatic Pancreatic Cancer (Stage III/IV)	Patients (Karnofsky performance status ≥70) were recruited and dosed with RXC004 (2 mg once daily [QD] orally) within 6 weeks of progression following 1st line Standard of Care (SoC) treatment.
OG001	Module 2-Advanced (Unresectable)/Metastatic Biliary Tract Cancer (Stage III/IV)	Patients (Eastern Cooperative Oncology Group [ECOG] performance status 0-1) were recruited and dosed with RXC004 within 6 weeks of progression following 1st line SoC treatment.
OG002	Module 3-Advanced (Unresectable)/Metastatic Biliary Tract Cancer (Stage Ill/IV) Combination Therapy	Patients (ECOG performance status 0-1) were 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.

Secondary

Minimum Observed Concentration Across the Dosing Interval (Cmin)

The PK (Cmin) of RXC004 as a monotherapy and as a combination therapy was assessed.

PK Analysis Set included all patients in the safety analysis set who have had at least one blood sample.

Posted

Geometric Mean

Geometric Coefficient of Variation

ng/mL

At Cycle 1 Day 15 (The cycle was 21 days in length) (Up to 23 months)

ID	Title	Description
OG000	Module 1-RNF43 Mutated Advanced (Unresectable)/Metastatic Pancreatic Cancer (Stage III/IV)	Patients (Karnofsky performance status ≥70) were recruited and dosed with RXC004 (2 mg once daily [QD] orally) within 6 weeks of progression following 1st line Standard of Care (SoC) treatment.
OG001	Module 2-Advanced (Unresectable)/Metastatic Biliary Tract Cancer (Stage III/IV)	Patients (Eastern Cooperative Oncology Group [ECOG] performance status 0-1) were recruited and dosed with RXC004 within 6 weeks of progression following 1st line SoC treatment.
OG002	Module 3-Advanced (Unresectable)/Metastatic Biliary Tract Cancer (Stage Ill/IV) Combination Therapy	Patients (ECOG performance status 0-1) were 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.

Secondary

Terminal Rate Constant (λz)

The PK (λz) of RXC004 as a monotherapy and as a combination therapy was assessed.

PK Analysis Set included all patients in the safety analysis set who have had at least one blood sample.

Posted

Geometric Mean

Geometric Coefficient of Variation

one per hour (1/h)

At Cycle 0 Day 1 (The cycle was 21 days in length)

ID	Title	Description
OG000	Module 1-RNF43 Mutated Advanced (Unresectable)/Metastatic Pancreatic Cancer (Stage III/IV)	Patients (Karnofsky performance status ≥70) were recruited and dosed with RXC004 (2 mg once daily [QD] orally) within 6 weeks of progression following 1st line Standard of Care (SoC) treatment.
OG001	Module 2-Advanced (Unresectable)/Metastatic Biliary Tract Cancer (Stage III/IV)	Patients (Eastern Cooperative Oncology Group [ECOG] performance status 0-1) were recruited and dosed with RXC004 within 6 weeks of progression following 1st line SoC treatment.
OG002	Module 3-Advanced (Unresectable)/Metastatic Biliary Tract Cancer (Stage Ill/IV) Combination Therapy	Patients (ECOG performance status 0-1) were 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.

Secondary

Terminal Half-life (t½)

The PK (t½) of RXC004 as a monotherapy and as a combination therapy was assessed.

PK Analysis Set included all patients in the safety analysis set who have had at least one blood sample.

Posted

Geometric Mean

Geometric Coefficient of Variation

hour (h)

At Cycle 0 Day 1(The cycle was 21 days in length)

ID	Title	Description
OG000	Module 1-RNF43 Mutated Advanced (Unresectable)/Metastatic Pancreatic Cancer (Stage III/IV)	Patients (Karnofsky performance status ≥70) were recruited and dosed with RXC004 (2 mg once daily [QD] orally) within 6 weeks of progression following 1st line Standard of Care (SoC) treatment.
OG001	Module 2-Advanced (Unresectable)/Metastatic Biliary Tract Cancer (Stage III/IV)	Patients (Eastern Cooperative Oncology Group [ECOG] performance status 0-1) were recruited and dosed with RXC004 within 6 weeks of progression following 1st line SoC treatment.
OG002	Module 3-Advanced (Unresectable)/Metastatic Biliary Tract Cancer (Stage Ill/IV) Combination Therapy	Patients (ECOG performance status 0-1) were 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.

Secondary

Area Under the Plasma Concentration-time Curve From Zero to Infinity (AUC0-∞)

The PK (AUC0-∞) of RXC004 as a monotherapy and as a combination therapy was assessed.

PK Analysis Set included all patients in the safety analysis set who have had at least one blood sample.

Posted

Geometric Mean

Geometric Coefficient of Variation

hour*nanogram per milliliter (h*ng/mL)

At Cycle 0 Day 1 (The cycle was 21 days in length)

ID	Title	Description
OG000	Module 1-RNF43 Mutated Advanced (Unresectable)/Metastatic Pancreatic Cancer (Stage III/IV)	Patients (Karnofsky performance status ≥70) were recruited and dosed with RXC004 (2 mg once daily [QD] orally) within 6 weeks of progression following 1st line Standard of Care (SoC) treatment.
OG001	Module 2-Advanced (Unresectable)/Metastatic Biliary Tract Cancer (Stage III/IV)	Patients (Eastern Cooperative Oncology Group [ECOG] performance status 0-1) were recruited and dosed with RXC004 within 6 weeks of progression following 1st line SoC treatment.
OG002	Module 3-Advanced (Unresectable)/Metastatic Biliary Tract Cancer (Stage Ill/IV) Combination Therapy	Patients (ECOG performance status 0-1) were 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.

Secondary

Total Plasma Clearance After Oral Administration (CL/F)

The PK(CL/F) of RXC004 as a monotherapy and as a combination therapy was assessed.

PK Analysis Set included all patients in the safety analysis set who have had at least one blood sample.

Posted

Geometric Mean

Geometric Coefficient of Variation

milliliter per hour (mL/h)

At Cycle 0 Day 1 (The cycle was 21 days in length)

ID	Title	Description
OG000	Module 1-RNF43 Mutated Advanced (Unresectable)/Metastatic Pancreatic Cancer (Stage III/IV)	Patients (Karnofsky performance status ≥70) were recruited and dosed with RXC004 (2 mg once daily [QD] orally) within 6 weeks of progression following 1st line Standard of Care (SoC) treatment.
OG001	Module 2-Advanced (Unresectable)/Metastatic Biliary Tract Cancer (Stage III/IV)	Patients (Eastern Cooperative Oncology Group [ECOG] performance status 0-1) were recruited and dosed with RXC004 within 6 weeks of progression following 1st line SoC treatment.
OG002	Module 3-Advanced (Unresectable)/Metastatic Biliary Tract Cancer (Stage Ill/IV) Combination Therapy	Patients (ECOG performance status 0-1) were 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.

Secondary

Apparent Volume of Distribution After Oral Administration (Vz/F)

The PK (Vz/F) of RXC004 as a monotherapy and as a combination therapy was assessed.

PK Analysis Set included all patients in the safety analysis set who have had at least one blood sample.

Posted

Geometric Mean

Geometric Coefficient of Variation

milliliter (mL)

At Cycle 0 Day 1 (The cycle was 21 days in length)

ID	Title	Description
OG000	Module 1-RNF43 Mutated Advanced (Unresectable)/Metastatic Pancreatic Cancer (Stage III/IV)	Patients (Karnofsky performance status ≥70) were recruited and dosed with RXC004 (2 mg once daily [QD] orally) within 6 weeks of progression following 1st line Standard of Care (SoC) treatment.
OG001	Module 2-Advanced (Unresectable)/Metastatic Biliary Tract Cancer (Stage III/IV)	Patients (Eastern Cooperative Oncology Group [ECOG] performance status 0-1) were recruited and dosed with RXC004 within 6 weeks of progression following 1st line SoC treatment.
OG002	Module 3-Advanced (Unresectable)/Metastatic Biliary Tract Cancer (Stage Ill/IV) Combination Therapy	Patients (ECOG performance status 0-1) were 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.

Secondary

Number of Patients With Adverse Events (AEs)

The safety, and tolerability profile of RXC004 as a monotherapy and as a combination therapy was assessed. The grading scales found in the revised National Cancer Institute CTCAE latest version was utilized for all events with an assigned CTCAE grading. Grade refers to the severity of the AE. The CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental ADL. Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL; Grade 4: Life-threatening, urgent intervention required; Grade 5: Death related to AE.

Safety Set included all patients who enrolled and received at least one dose of RXC004 in Modules 1 and 2, and at least one dose of RXC004 or pembrolizumab in Module 3.

Posted

Count of Participants

Participants

From time of signature of main study informed consent form throughout the treatment period and until the 30 days after last dose of RXC004 (Up to 23 months)

ID	Title	Description
OG000	Module 1-RNF43 Mutated Advanced (Unresectable)/Metastatic Pancreatic Cancer (Stage III/IV)	Patients (Karnofsky performance status ≥70) were recruited and dosed with RXC004 (2 mg once daily [QD] orally) within 6 weeks of progression following 1st line Standard of Care (SoC) treatment.

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Module 1-RNF43 Mutated Advanced (Unresectable)/Metastatic Pancreatic Cancer (Stage III/IV)	Patients (Karnofsky performance status ≥70) were recruited and dosed with RXC004 (2 mg once daily [QD] orally) within 6 weeks of progression following 1st line Standard of Care (SoC) treatment.	5	6	3	6	6	6
EG001	Module 2-Advanced (Unresectable)/Metastatic Biliary Tract Cancer (Stage III/IV)	Patients (Eastern Cooperative Oncology Group [ECOG] performance status 0-1) were recruited and dosed with RXC004 within 6 weeks of progression following 1st line SoC treatment.	15	20	6	20	20	20
EG002	Module 3-Advanced (Unresectable)/Metastatic Biliary Tract Cancer (Stage Ill/IV) Combination Therapy	Patients (ECOG performance status 0-1) were 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.	10	19	11	19	19	19

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Gastric haemorrhage	Gastrointestinal disorders	MedDRA 26.1	Non-systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected20 at risk EG0020 events0 affected19 at risk
Cholangitis	Hepatobiliary disorders	MedDRA 26.1	Non-systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected20 at risk EG0020 events0 affected19 at risk
Sepsis	Infections and infestations	MedDRA 26.1	Non-systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected20 at risk EG0021 events1 affected19 at risk
Viral infection	Infections and infestations	MedDRA 26.1	Non-systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected20 at risk EG0020 events0 affected19 at risk
Diabetic ketoacidosis	Metabolism and nutrition disorders	MedDRA 26.1	Non-systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected20 at risk EG0020 events0 affected19 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA 26.1	Non-systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected20 at risk EG0021 events1 affected19 at risk
Anaemia	Blood and lymphatic system disorders	MedDRA 26.1	Non-systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected20 at risk EG0020 events0 affected19 at risk
Immune-mediated myocarditis	Cardiac disorders	MedDRA 26.1	Non-systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected20 at risk EG0021 events1 affected19 at risk
Immune-mediated adrenal insufficiency	Endocrine disorders	MedDRA 26.1	Non-systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected20 at risk EG0021 events1 affected19 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 26.1	Non-systematic Assessment	EG0000 events0 affected6 at risk EG0012 events2 affected20 at risk EG0021 events1 affected19 at risk
Colitis	Gastrointestinal disorders	MedDRA 26.1	Non-systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected20 at risk EG0022 events2 affected19 at risk
Upper gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 26.1	Non-systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected20 at risk EG0020 events0 affected19 at risk
Vomiting	Gastrointestinal disorders	MedDRA 26.1	Non-systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected20 at risk EG0020 events0 affected19 at risk
Pyrexia	General disorders	MedDRA 26.1	Non-systematic Assessment	EG0000 events0 affected6 at risk EG0012 events1 affected20 at risk EG0021 events1 affected19 at risk
Biliary obstruction	Hepatobiliary disorders	MedDRA 26.1	Non-systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected20 at risk EG0023 events2 affected19 at risk
Bacteraemia	Infections and infestations	MedDRA 26.1	Non-systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected20 at risk EG0021 events1 affected19 at risk
Biliary sepsis	Infections and infestations	MedDRA 26.1	Non-systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected20 at risk EG0021 events1 affected19 at risk
Biliary tract infection	Infections and infestations	MedDRA 26.1	Non-systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected20 at risk EG0021 events1 affected19 at risk
Stoma site abscess	Infections and infestations	MedDRA 26.1	Non-systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected20 at risk EG0021 events1 affected19 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 26.1	Non-systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected20 at risk EG0020 events0 affected19 at risk
Dizziness	Nervous system disorders	MedDRA 26.1	Non-systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected20 at risk EG0021 events1 affected19 at risk
Lacunar stroke	Nervous system disorders	MedDRA 26.1	Non-systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected20 at risk EG0021 events1 affected19 at risk
Myasthenia gravis	Nervous system disorders	MedDRA 26.1	Non-systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected20 at risk EG0021 events1 affected19 at risk
Device occlusion	Product Issues	MedDRA 26.1	Non-systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected20 at risk EG0021 events1 affected19 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA 26.1	Non-systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected20 at risk EG0021 events1 affected19 at risk
Duodenal obstruction	Gastrointestinal disorders	MedDRA 26.1	Non-systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected20 at risk EG0020 events0 affected19 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Diarrhoea	Gastrointestinal disorders	MedDRA 26.1	Non-systematic Assessment	EG0003 events3 affected6 at risk EG0018 events5 affected20 at risk EG0024 events4 affected19 at risk
Constipation	Gastrointestinal disorders	MedDRA 26.1	Non-systematic Assessment	EG0002 events2 affected6 at risk EG0019 events8 affected20 at risk EG0028 events6 affected19 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 26.1	Non-systematic Assessment	EG0001 events1 affected6 at risk EG0014 events4 affected20 at risk EG0023 events3 affected19 at risk
Dry mouth	Gastrointestinal disorders	MedDRA 26.1	Non-systematic Assessment	EG0001 events1 affected6 at risk EG0012 events2 affected20 at risk EG0022 events2 affected19 at risk
Vomiting	Gastrointestinal disorders	MedDRA 26.1	Non-systematic Assessment	EG0001 events1 affected6 at risk EG00111 events10 affected20 at risk EG0025 events5 affected19 at risk
Chills	General disorders	MedDRA 26.1	Non-systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected20 at risk EG0020 events0 affected19 at risk
Blood creatinine increased	Investigations	MedDRA 26.1	Non-systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected20 at risk EG0023 events3 affected19 at risk
Weight decreased	Investigations	MedDRA 26.1	Non-systematic Assessment	EG0001 events1 affected6 at risk EG0013 events3 affected20 at risk EG0021 events1 affected19 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 26.1	Non-systematic Assessment	EG0003 events3 affected6 at risk EG0013 events3 affected20 at risk EG0026 events6 affected19 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 26.1	Non-systematic Assessment	EG0002 events2 affected6 at risk EG0011 events1 affected20 at risk EG0024 events4 affected19 at risk
Hypocalcaemia	Metabolism and nutrition disorders	MedDRA 26.1	Non-systematic Assessment	EG0001 events1 affected6 at risk EG0011 events1 affected20 at risk EG0022 events2 affected19 at risk
Joint stiffness	Musculoskeletal and connective tissue disorders	MedDRA 26.1	Non-systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected20 at risk EG0020 events0 affected19 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 26.1	Non-systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected20 at risk EG0020 events0 affected19 at risk
Dysgeusia	Nervous system disorders	MedDRA 26.1	Non-systematic Assessment	EG0005 events5 affected6 at risk EG00114 events13 affected20 at risk EG00213 events12 affected19 at risk
Headache	Nervous system disorders	MedDRA 26.1	Non-systematic Assessment	EG0002 events2 affected6 at risk EG0011 events1 affected20 at risk EG0021 events1 affected19 at risk
Disturbance in attention	Nervous system disorders	MedDRA 26.1	Non-systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected20 at risk EG0020 events0 affected19 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 26.1	Non-systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected20 at risk EG0024 events4 affected19 at risk
Anaemia	Blood and lymphatic system disorders	MedDRA 26.1	Non-systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected20 at risk EG0026 events4 affected19 at risk
Lymphopenia	Blood and lymphatic system disorders	MedDRA 26.1	Non-systematic Assessment	EG0000 events0 affected6 at risk EG0012 events2 affected20 at risk EG0021 events1 affected19 at risk
Coagulopathy	Blood and lymphatic system disorders	MedDRA 26.1	Non-systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected20 at risk EG0021 events1 affected19 at risk
Hypothyroidism	Endocrine disorders	MedDRA 26.1	Non-systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected20 at risk EG0020 events0 affected19 at risk
Immune-mediated thyroiditis	Endocrine disorders	MedDRA 26.1	Non-systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected20 at risk EG0021 events1 affected19 at risk
Conjunctival haemorrhage	Eye disorders	MedDRA 26.1	Non-systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected20 at risk EG0020 events0 affected19 at risk
Dry eye	Eye disorders	MedDRA 26.1	Non-systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected20 at risk EG0020 events0 affected19 at risk
Vitreous floaters	Eye disorders	MedDRA 26.1	Non-systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected20 at risk EG0020 events0 affected19 at risk
Nausea	Gastrointestinal disorders	MedDRA 26.1	Non-systematic Assessment	EG0000 events0 affected6 at risk EG00114 events13 affected20 at risk EG0025 events5 affected19 at risk
Colitis	Gastrointestinal disorders	MedDRA 26.1	Non-systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected20 at risk EG0021 events1 affected19 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA 26.1	Non-systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected20 at risk EG0022 events2 affected19 at risk
Ascites	Gastrointestinal disorders	MedDRA 26.1	Non-systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected20 at risk EG0020 events0 affected19 at risk
Duodenal ulcer	Gastrointestinal disorders	MedDRA 26.1	Non-systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected20 at risk EG0021 events1 affected19 at risk
Gastrointestinal pain	Gastrointestinal disorders	MedDRA 26.1	Non-systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected20 at risk EG0021 events1 affected19 at risk
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA 26.1	Non-systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected20 at risk EG0022 events2 affected19 at risk
Gingival bleeding	Gastrointestinal disorders	MedDRA 26.1	Non-systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected20 at risk EG0021 events1 affected19 at risk
Oesophagitis	Gastrointestinal disorders	MedDRA 26.1	Non-systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected20 at risk EG0021 events1 affected19 at risk
Steatorrhoea	Gastrointestinal disorders	MedDRA 26.1	Non-systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected20 at risk EG0020 events0 affected19 at risk
Toothache	Gastrointestinal disorders	MedDRA 26.1	Non-systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected20 at risk EG0021 events1 affected19 at risk
Fatigue	General disorders	MedDRA 26.1	Non-systematic Assessment	EG0002 events2 affected6 at risk EG0019 events9 affected20 at risk EG0029 events8 affected19 at risk
Pyrexia	General disorders	MedDRA 26.1	Non-systematic Assessment	EG0000 events0 affected6 at risk EG0014 events4 affected20 at risk EG0022 events2 affected19 at risk
Oedema peripheral	General disorders	MedDRA 26.1	Non-systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected20 at risk EG0022 events2 affected19 at risk
Hepatic pain	Hepatobiliary disorders	MedDRA 26.1	Non-systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected20 at risk EG0020 events0 affected19 at risk
Hypertransaminasaemia	Hepatobiliary disorders	MedDRA 26.1	Non-systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected20 at risk EG0020 events0 affected19 at risk
Hypersensitivity	Immune system disorders	MedDRA 26.1	Non-systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected20 at risk EG0020 events0 affected19 at risk
Oral candidiasis	Infections and infestations	MedDRA 26.1	Non-systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected20 at risk EG0022 events2 affected19 at risk
COVID-19	Infections and infestations	MedDRA 26.1	Non-systematic Assessment	EG0000 events0 affected6 at risk EG0013 events3 affected20 at risk EG0021 events1 affected19 at risk
Urinary tract infection	Infections and infestations	MedDRA 26.1	Non-systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected20 at risk EG0023 events1 affected19 at risk
Bacterial infection	Infections and infestations	MedDRA 26.1	Non-systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected20 at risk EG0021 events1 affected19 at risk
Cystitis	Infections and infestations	MedDRA 26.1	Non-systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected20 at risk EG0020 events0 affected19 at risk
Influenza	Infections and infestations	MedDRA 26.1	Non-systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected20 at risk EG0020 events0 affected19 at risk
Lower respiratory tract infection	Infections and infestations	MedDRA 26.1	Non-systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected20 at risk EG0021 events1 affected19 at risk
Lung abscess	Infections and infestations	MedDRA 26.1	Non-systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected20 at risk EG0021 events1 affected19 at risk
Lymphangitis	Infections and infestations	MedDRA 26.1	Non-systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected20 at risk EG0021 events1 affected19 at risk
Nasal herpes	Infections and infestations	MedDRA 26.1	Non-systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected20 at risk EG0020 events0 affected19 at risk
Oral herpes	Infections and infestations	MedDRA 26.1	Non-systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected20 at risk EG0020 events0 affected19 at risk
Pneumonia	Infections and infestations	MedDRA 26.1	Non-systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected20 at risk EG0021 events1 affected19 at risk
Respiratory tract infection	Infections and infestations	MedDRA 26.1	Non-systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected20 at risk EG0020 events0 affected19 at risk
Immunisation reaction	Injury, poisoning and procedural complications	MedDRA 26.1	Non-systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected20 at risk EG0020 events0 affected19 at risk
Procedural pain	Injury, poisoning and procedural complications	MedDRA 26.1	Non-systematic Assessment	EG0000 events0 affected6 at risk EG0012 events2 affected20 at risk EG0020 events0 affected19 at risk
Blood bilirubin increased	Investigations	MedDRA 26.1	Non-systematic Assessment	EG0000 events0 affected6 at risk EG0013 events3 affected20 at risk EG0026 events4 affected19 at risk
Alanine aminotransferase increased	Investigations	MedDRA 26.1	Non-systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected20 at risk EG0024 events3 affected19 at risk
Blood alkaline phosphatase increased	Investigations	MedDRA 26.1	Non-systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected20 at risk EG0024 events4 affected19 at risk
Aspartate aminotransferase increased	Investigations	MedDRA 26.1	Non-systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected20 at risk EG0021 events1 affected19 at risk
Blood magnesium decreased	Investigations	MedDRA 26.1	Non-systematic Assessment	EG0000 events0 affected6 at risk EG0012 events2 affected20 at risk EG0020 events0 affected19 at risk
Blood phosphorus decreased	Investigations	MedDRA 26.1	Non-systematic Assessment	EG0000 events0 affected6 at risk EG0012 events2 affected20 at risk EG0020 events0 affected19 at risk
Blood calcium increased	Investigations	MedDRA 26.1	Non-systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected20 at risk EG0021 events1 affected19 at risk
Blood urea increased	Investigations	MedDRA 26.1	Non-systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected20 at risk EG0021 events1 affected19 at risk
International normalised ratio increased	Investigations	MedDRA 26.1	Non-systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected20 at risk EG0020 events0 affected19 at risk
Hypophosphataemia	Metabolism and nutrition disorders	MedDRA 26.1	Non-systematic Assessment	EG0000 events0 affected6 at risk EG0013 events3 affected20 at risk EG0024 events4 affected19 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 26.1	Non-systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected20 at risk EG0022 events2 affected19 at risk
Hypomagnesaemia	Metabolism and nutrition disorders	MedDRA 26.1	Non-systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected20 at risk EG0021 events1 affected19 at risk
Hypercalcaemia	Metabolism and nutrition disorders	MedDRA 26.1	Non-systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected20 at risk EG0020 events0 affected19 at risk
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA 26.1	Non-systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected20 at risk EG0020 events0 affected19 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 26.1	Non-systematic Assessment	EG0000 events0 affected6 at risk EG0013 events3 affected20 at risk EG0023 events3 affected19 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 26.1	Non-systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected20 at risk EG0021 events1 affected19 at risk
Flank pain	Musculoskeletal and connective tissue disorders	MedDRA 26.1	Non-systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected20 at risk EG0021 events1 affected19 at risk
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	MedDRA 26.1	Non-systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected20 at risk EG0021 events1 affected19 at risk
Myositis	Musculoskeletal and connective tissue disorders	MedDRA 26.1	Non-systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected20 at risk EG0021 events1 affected19 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 26.1	Non-systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected20 at risk EG0021 events1 affected19 at risk
Arachnoid cyst	Nervous system disorders	MedDRA 26.1	Non-systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected20 at risk EG0021 events1 affected19 at risk
Neuropathy peripheral	Nervous system disorders	MedDRA 26.1	Non-systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected20 at risk EG0020 events0 affected19 at risk
Restless legs syndrome	Nervous system disorders	MedDRA 26.1	Non-systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected20 at risk EG0020 events0 affected19 at risk
Insomnia	Psychiatric disorders	MedDRA 26.1	Non-systematic Assessment	EG0000 events0 affected6 at risk EG0012 events2 affected20 at risk EG0023 events3 affected19 at risk
Depression	Psychiatric disorders	MedDRA 26.1	Non-systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected20 at risk EG0021 events1 affected19 at risk
Chromaturia	Renal and urinary disorders	MedDRA 26.1	Non-systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected20 at risk EG0021 events1 affected19 at risk
Urinary hesitation	Renal and urinary disorders	MedDRA 26.1	Non-systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected20 at risk EG0021 events1 affected19 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 26.1	Non-systematic Assessment	EG0000 events0 affected6 at risk EG0012 events2 affected20 at risk EG0022 events2 affected19 at risk
Dysphonia	Respiratory, thoracic and mediastinal disorders	MedDRA 26.1	Non-systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected20 at risk EG0022 events2 affected19 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 26.1	Non-systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected20 at risk EG0021 events1 affected19 at risk
Pleuritic pain	Respiratory, thoracic and mediastinal disorders	MedDRA 26.1	Non-systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected20 at risk EG0021 events1 affected19 at risk
Alopecia	Skin and subcutaneous tissue disorders	MedDRA 26.1	Non-systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected20 at risk EG0022 events2 affected19 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA 26.1	Non-systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected20 at risk EG0021 events1 affected19 at risk
Dry skin	Skin and subcutaneous tissue disorders	MedDRA 26.1	Non-systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected20 at risk EG0020 events0 affected19 at risk
Erythema	Skin and subcutaneous tissue disorders	MedDRA 26.1	Non-systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected20 at risk EG0021 events1 affected19 at risk
Nail discolouration	Skin and subcutaneous tissue disorders	MedDRA 26.1	Non-systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected20 at risk EG0021 events1 affected19 at risk
Onychomadesis	Skin and subcutaneous tissue disorders	MedDRA 26.1	Non-systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected20 at risk EG0020 events0 affected19 at risk
Purpura	Skin and subcutaneous tissue disorders	MedDRA 26.1	Non-systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected20 at risk EG0020 events0 affected19 at risk
Rash maculo-papular	Skin and subcutaneous tissue disorders	MedDRA 26.1	Non-systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected20 at risk EG0021 events1 affected19 at risk
Hypotension	Vascular disorders	MedDRA 26.1	Non-systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected20 at risk EG0020 events0 affected19 at risk
Thrombophlebitis	Vascular disorders	MedDRA 26.1	Non-systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected20 at risk EG0020 events0 affected19 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA 26.1	Non-systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected20 at risk EG0020 events0 affected19 at risk
Pulmonary haemorrhage	Respiratory, thoracic and mediastinal disorders	MedDRA 26.1	Non-systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected20 at risk EG0020 events0 affected19 at risk
Groin pain	Musculoskeletal and connective tissue disorders	MedDRA 26.1	Non-systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected20 at risk EG0020 events0 affected19 at risk
Acute kidney injury	Renal and urinary disorders	MedDRA 26.1	Non-systematic Assessment	EG0001 events1 affected6 at risk EG0011 events1 affected20 at risk EG0020 events0 affected19 at risk
Hypoalbuminaemia	Metabolism and nutrition disorders	MedDRA 26.1	Non-systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected20 at risk EG0022 events2 affected19 at risk
Biliary obstruction	Hepatobiliary disorders	MedDRA 26.1	Non-systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected20 at risk EG0021 events1 affected19 at risk

ID	Term
D001661	Biliary Tract Neoplasms
D010190	Pancreatic Neoplasms
D018281	Cholangiocarcinoma

Ancestor Terms

ID	Term
D004067	Digestive System Neoplasms
D009371	Neoplasms by Site
D009369	Neoplasms
D001660	Biliary Tract Diseases
D004066	Digestive System Diseases
D004701	Endocrine Gland Neoplasms
D010182	Pancreatic Diseases
D004700	Endocrine System Diseases
D000230	Adenocarcinoma
D002277	Carcinoma
D009375	Neoplasms, Glandular and Epithelial
D009370	Neoplasms by Histologic Type

ID	Term
D000069448	Denosumab
C582435	pembrolizumab

Ancestor Terms

ID	Term
D061067	Antibodies, Monoclonal, Humanized
D000911	Antibodies, Monoclonal
D000906	Antibodies
D007136	Immunoglobulins
D007162	Immunoproteins
D001798	Blood Proteins
D011506	Proteins
D000602	Amino Acids, Peptides, and Proteins
D012712	Serum Globulins
D005916	Globulins

Patients (ECOG performance status 0-1) were recruited and dosed with RXC004 (1.5 mg QD orally) in combination with pembrolizumab 400 mg IV infusion q6w within 6 weeks of progression following 1st line SoC treatment.