1. COMBI RECIST 1.1 February 2013

2. Target Lesions: Selection at Baseline Perform baseline evaluations as close to treatment start as possible (no more than 4 weeks prior) View all available imaging before selecting target lesions Select up to 5 in total; maximum of 2 lesions per organ –Measure short axis of lymph nodes and longest diameter of non lymph nodes Target selection should be based on: –Lesion size –Representation of all organs –Likely reliability/reproducibility of repeated measurement Clinical evaluations: –Use calipers or ruler and color photography –If a lesion can be evaluated via either imaging or clinical exam, use imaging

3. Target Lesion: Selection at Baseline (continued) GSK recommends the following not be selected as target lesions when other suitable lesions are available –Lymph nodes –Cystic lesions thought to represent cystic metastases Measurable lesions that have been previously irradiated and have not been shown to be progressing following irradiation should not be considered as target lesions Note: Any lesions not selected as target lesions should be reported as non target lesions.

4. Target Lesion: Follow-up Assessment Ensure consistent assessment modality across visits (same equipment where possible, same contrast timing, and same output medium, e.g. electronic image) Target lymph nodes : –Continue to collect actual measurement, even if < 10 mm. –Sum of lesion diameter may not be zero, yet CR is still possible because lymph nodes < 10mm are considered non pathologic Lesions (Non Lymph nodes): –All baseline target lesions should have actual follow-up measurements recorded, even if very small (e.g., 2 mm) –If truly too small to measure but not absent 5 mm should be recorded and should contribute to the sum of the diameters –If it is likely the lesion has disappeared 0mm should be reported

5. Target Lesion: if all Lesions Identified at Baseline are Not Assessed? SUMLD cannot be calculated for purposes of assessing CR, PR, or SD or for use as the nadir for future assessments. SUMLD of the assessed lesions and the percent change from nadir should be calculated to ensure that progression has not been documented. If an assessment of PD cannot be made, the response assessment should be NE.

6. Non-Target Lesion: Selection at Baseline Includes: –All truly non-measurable lesions (bone, effusions, etc.) –Lesions with Diameter <10 mm (or < 2x slice thickness) –Pathological Lymph Nodes with short axis ≥10mm and <15mm –All remaining measurable lesions not reported as target Measurements not required Record multiple non-target lesions involving the same organ as a single item –Multiple liver metastases

7. Non-Target Lesion: Follow-up Assessment Present Absent Unequivocal progression –If patient has measurable and non-measurable disease: Modest increase in one or more non-targets is not usually sufficient to qualify as unequivocal PD Must exhibit worsening in tumor burden sufficient enough to warrant treatment discontinuation even if targets are in PR or SD –If patient only has non-measurable disease: Consider whether change is comparable in magnitude to change required for PD in measurable disease –E.g., 73% increase in volume= 20% increase in Sum of Diameters –Pleural effusion changing from “trace” to “large” Progression sufficient enough to warrant change in treatment

8. New Lesions: Unequivocal New Lesions New malignancies denoting disease progression must be unequivocal Not attributable to different scanning techniques: –E.g. change in modality or imaging parameters Not thought to represent something other than tumour (e.g. some ‘new’ bone lesions may be simply healing or flare of pre- existing lesions) Lesions identified at follow-up in an anatomical location that was not scanned at baseline should be considered new lesions –E.g., positive brain MRI on study with no brain MRI at baseline