Inclusion Criteria:

1. Histopathological/cytological diagnosis of non-resectable, recurrent or metastatic
colorectal cancer

2. Tumour with wild-type KRAS

3. Measurable disease evaluated by RECIST criteria v1.1

4. WHO performance status 0 or 1

5. Age ≥ 18

6. Estimated life expectancy > 3 months

7. Adequate haematological function:

- Haemoglobin ≥100 g/L

- WBC ≥3.0 x 10^9/L

- Absolute neutrophil count ≥1.5 x 10^9/L

- Platelet count ≥100 x 10^9/L

8. Adequate liver function:

- Total bilirubin ≤1.5 x upper limit of normal (ULN)

- ALT, AST & ALP ≤2.5 x ULN in the absence of noted liver metastases

- ALT, AST & ALP ≤5 x ULN in the presence of liver metastases

9. Adequate renal function:

- Serum creatinine ≤1.5 x ULN

- Calculated creatinine clearance ≥30 mL/min

10. Adequate biliary drainage (patients with stents are eligible)

11. Adequate venous access for collection of exploratory biological samples

12. Women of child-bearing potential must have a negative pregnancy test prior to study
entry. Female patients and male patients with partners of child-bearing potential
must agree to use an adequate contraception method, which must be continued for 6
months after completion of chemotherapy

13. Must be able to swallow AZD8931 tablets

14. Capable of giving written informed consent

15. The following prior therapy is allowed:

- Surgery - patients may have undergone a non-curative operation or palliative
bypass surgery only. Patients who have previously undergone curative surgery
must have evidence of non-resectable disease relapse

- Radiotherapy - for localised disease

- Prior adjuvant chemotherapy - provided this was completed at least 6 months
before trial entry

Exclusion Criteria:

1. Patients undergoing treatment with curative intent

2. Any prior treatment with agents targeting the ERBB pathway

3. Treatment with experimental drugs within 30 days or 5 half-lives of first dose of
AZD8931

4. Previous chemotherapy for metastatic disease

5. Prior treatment with anthracyclines or mitoxantrone

6. Current disease or condition known to interfere with absorption, distribution,
metabolism or excretion of drugs (including refractory nausea and vomiting, chronic
gastrointestinal disease (e.g. inflammatory bowel disease), or significant bowel
resection)

7. History of prior malignancy that will interfere with the response evaluation
(exceptions listed in protocol)

8. Evidence of severe/uncontrolled systemic diseases or laboratory finding that makes it
undesirable for the patient to participate in the trial

9. Evidence of active uncontrolled infection

10. Patients with clinically significant ascites and/or effusions

11. Regular use of anti-diarrhoeal

12. Pregnant or lactating women

13. Cardiac conditions (as detailed in the trial protocol)

14. Any psychiatric or other disorder (e.g. brain metastases) likely to impact the
ability to give informed consent

15. Eye conditions (as detailed in the trial protocol)

16. Patients with chronic skin conditions e.g. acne rosacea, psoriasis, severe atopic
eczema

17. Past medical history of interstitial lung disease, drug-induced interstitial lung
disease, radiation pneumonitis which required steroid treatment, or any evidence of
clinically active interstitial lung disease

18. History or repeated unexplained episodes of syncope/dizziness

19. Known hypersensitivity to AZD8931, its excipients, or drugs in its class

20. The use of drugs/substances known to inhibit or induce CYP3A4 or CYP2D6, or those
known to prolong QT interval, which cannot be discontinued for the duration of trial
treatment

21. Patients with hereditary fructose intolerance