Table 2 Schedule of assessments and procedures

Cycle

Within 28 days before start therapy

Within 14 days before start therapy

Cycle3

Cycle4

Cycle5

Cycle6

Cycle7+

At progression (EoS)

Every 12 weeks

Day

1

14

15

1

21

1 (± 3)

1 (± 3)

1 (± 3)

1 (± 3)

1 (± 3)

Within 7 days (on therapy)

In- and exclusion criteria

X

Medical history and demographics

X

Interval medical history

X

X

X

X

X

X

X

X

X

X

X

Physical examination

X

X

X

X

X

X

X

X

X

X

X

X

Vital signs (Temp, HR, RR)

X

X

X

X

X

X

X

X

X

Pregnancy test (if indicated)

X

Dermatologic examination

X

X

X

X

X

Ophthalmologic examination

if indicated

MUGA scan

X

X

X

X

X

12-lead electrocardiography (ECG)

X

X

X

X

X

X

X

X

Contrast Enhanced CT (CECT)

X

X

X

X

X

X

X

X

ECOG performance status

X

X

X

X

X

X

X

X

X

X

X

X

Blood samples

X

X

X

X

X

X

X

X

X

X

X

Informed consent

X

PK blood sample

X

X

X

DNA blood sample (Substudy 1 and 2)

X

X

¹⁸F-FLT PET (Substudy 1)

X

X

X

¹⁸F-FDG PET

X

X

X

X

Tumor biopsy (Substudy 1 and 2)

X

X

X

Adverse events

X

X

X

X

X

X

X

X

X

X

X

Start vemurafenib cobimetinib

X