A Study to Assess Efficacy of RXC004 +/- Nivolumab in Ring Finger Protein 43 (RNF43) or R-spondin (RSPO) Aberrated, Metastatic, Microsatellite Stable, Colorectal Cancer After Progression on Standard of Care (SOC)

Best Percentage Change in Tumor Size

The preliminary efficacy of RXC004 monotherapy and combination therapy of RXC004 + nivolumab was evaluated. The best percentage change in tumour size was determined at a patient level. Percentage change in tumour size was derived at each visit by the percentage change from baseline in the sum of diameters of target lesions. The best percentage change in tumour size was the patients value representing the largest decrease (or smallest increase) from baseline in tumour size.

Time frame: Up to 28 months

Progression Free Survival (PFS)

The preliminary efficacy of RXC004 monotherapy and combination therapy of RXC004 + nivolumab was evaluated. PFS is 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).

Time frame: Up to 28 months

Duration of Response (DOR)

The preliminary efficacy of RXC004 monotherapy and combination therapy of RXC004 + nivolumab was evaluated. The DOR is as the time from the date of first documented response until date of documented progression or death in the absence of disease progression. DOR was not calculated as 1 patient had PR, and 0 patient had CR. As pre-specified in the SAP that after the review of the available data, DOR would not be summarized and listed.

Time frame: Up to 28 months

RXC004 Monotherapy (Arm A): Objective Response Rate (ORR) Using Investigator Assessments According to RECIST 1.1

The preliminary efficacy of RXC004 monotherapy was evaluated. ORR is defined as the percentage of patients with a BOR of CR or PR based on local investigator assessment as defined in RECIST 1.1.

Time frame: Up to 28 months

RXC004 + Nivolumab Combination Therapy (Arm B): Disease Control Rate Using Investigator Assessments According to RECIST 1.1

The preliminary efficacy of combination therapy of RXC004 + nivolumab was evaluated. DCR is defined as the percentage of patients with a BOR of either CR, PR or SD for at least 16 weeks post baseline.

Time frame: Up to 28 months

Overall Survival (OS)

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

Time frame: Up to 28 months

Maximum Observed Plasma Concentration (Cmax)

The pharmacokinetic (PK) (Cmax) of RXC004 in monotherapy and in combination therapy with nivolumab was evaluated.

Time frame: On Cycle 0 Day 1 (3-7 days cycle in length) and Cycle 1 Day 15 (28 days cycle in length)

Time to Maximum Plasma Concentration (Tmax)

The PK (Tmax) of RXC004 in monotherapy and in combination therapy with nivolumab was evaluated.

Time frame: On Cycle 0 Day 1 (3-7 days cycle in length) and Cycle 1 Day 15 (28 days cycle in length)

Minimum Observed Concentration Across the Dosing Interval (Cmin)

The PK (Cmin) of RXC004 in monotherapy and in combination therapy with nivolumab was evaluated.

Time frame: On Cycle 1 Day 15 (28 days cycle in length)

Terminal Rate Constant (λz)

The PK (λz) of RXC004 in monotherapy and in combination therapy with nivolumab was evaluated.

Time frame: On Cycle 0 Day 1 (3-7 days cycle in length)

Terminal Half-life (t½)

The PK (t½) of RXC004 in monotherapy and in combination therapy with nivolumab was evaluated.

Time frame: On Cycle 0 Day 1 (3-7 days cycle in length)

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

The PK (AUC0-∞) of RXC004 in monotherapy and in combination therapy with nivolumab was evaluated.

Time frame: On Cycle 0 Day 1 (3-7 days cycle in length)

Total Plasma Clearance After Oral Administration (CL/F)

The PK (CL/F) of RXC004 in monotherapy and in combination therapy with nivolumab was evaluated.

Time frame: On Cycle 0 Day 1 (3-7 days cycle in length)

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

The PK (Vz/F) of RXC004 in monotherapy and in combination therapy with nivolumab was evaluated.

Time frame: On Cycle 0 Day 1 (3-7 days cycle in length)

Number of Patients With Adverse Events (AEs)

The safety and tolerability profile of RXC004 monotherapy and RXC004 + nivolumab combination was evaluated. The grading scales found in the revised National Cancer Institute Common Terminology Criteria for Adverse events (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.

Time frame: From time of signature of informed consent form throughout the treatment period and until 30 days after the last dose of RXC004 (for RXC004 monotherapy only) or 90 days after the last dose of Nivolumab (for RXC004 + nivolumab) (up to 28 months)