Inclusion Criteria

Inclusion criteria:

1. Patients with a histologically or cytologically confirmed diagnosis of an advanced
unresectable and/or metastatic solid tumour, and who have failed conventional
treatment or for whom no therapy of proven efficacy exists or who are not amenable to
standard therapies.

2. Age 18 years and older

3. Written informed consent consistent with ICH-GCP and local legislation

4. Eastern Cooperative Oncology Group (ECOG) performance score 0 or 1.

5. Recovery of therapy-related toxicities from previous anti-tumour therapies to Common
Terminology Criteria for Adverse Events (CTCAE) = grade 1 (with the exception of
alopecia).

6. Written informed consent to the use of archival tumour sample for determination of
the BRAF/RAS mutational status.

7. Life expectancy of at least 12 weeks.

8. In escalation phase, when PK close to predicted Cmax or when signs of PD modulation
present, optional tumour biopsies (at same timepoints as in expansion phase) for the
patients who consented to it.

In addition, all patients included in the expansion phase (part Ib) must:

9. have been diagnosed with one of the following tumours: melanoma, colorectal
carcinoma, Non Small Cell Lung Cancer (NSCLC) or exocrine pancreas adenocarcinoma,
and have been shown on their archival tumour sample to have KRAS or BRAF mutation.

10. have a measurable disease.

11. have documented/proven progressive disease within the last 6 months, according to
Response Evaluation Criteria In Solid Tumours (RECIST) criteria

11. have a tumour lesion accessible for biopsies (pre- and post-treatment): this is
mandatory for patients with colorectal carcinoma or melanoma, optional for patients with
NSCLC or exocrine pancreas adenocarcinoma.

Exclusion criteria:

1. Inability to swallow tablets.

2. Additional other serious illness , concomitant non-oncological disease (e.g. active
infectious disease or known chronic Hepatitis B/Hepatitis C infection and HIV), or
ongoing toxicity from prior therapies considered by the investigator to potentially
compromise patient's safety in this trial.

3. Clinical evidence of symptomatic progressive brain or leptomeningeal disease during
the last 28 days.

4. Second malignancy currently requiring another anti-cancer therapy.

5. Absolute neutrophil count less than 1500/mm3.

6. Platelet count less than 100 000/mm3.

7. Bilirubin greater than 1.5 mg/dL (>26 µmol/L, SI unit equivalent) (except known
Gilbert's syndrome).

8. Aspartate amino transferase (AST) and/or alanine amino transferase (ALT) greater than
2.5 times the upper limit of normal (if related to liver metastases, greater than
five times the upper limit of normal).

9. Serum creatinine greater than 1.5 mg/dL (>132 µmol/L, SI unit equivalent).

10. Previous episode of QT prolongation due to a medication which, as a result of it, had
to be discontinued; or long QT syndrome; or QTc with Fridericia's correction >480
msec on screening ECG.

11. Pregnancy or breastfeeding.

12. Women or men who are sexually active and unwilling to use a medically acceptable
method of contraception.

13. Treatment with other investigational drugs or participation in another clinical
interventional trial within the past four weeks before start of therapy or
concomitant with this trial.

14. Systemic anti-cancer therapy or radiotherapy within the past four weeks before start
of therapy or concomitantly with this trial. This restriction does not apply to LHRH
agonists, steroids and bisphosphonates.

15. Patients unable to comply with the protocol.

16. Active alcohol or drug abuse.

17. history or presence of cardiovascular abnormalities deemed clinically relevant by the
investigator. Myocardial infarction within 6 months prior to study.

18. Cardiac left ventricular ejection fraction <50% or less than institutional lower
limit of normal by MUGA or echocardiography