recist guidelines version 1.1 measurement
response criteria

Evaluation of Target Lesions  
| Complete Response (CR):                                 | Disappearance of all target lesions.  Any           |
|---------------------------------------------------------|-----------------------------------------------------|
| pathological lymph nodes (whether target or non¬        |                                                     |
| target) must have reduction in short axis to <10        |                                                     |
| m.                                                      |                                                     |
| Partial Response (PR):                                  | At least a 30% decrease in the sum of the diameters |
| of target lesions, taking as reference the baseline     |                                                     |
| sum diameters.                                          |                                                     |
| Progressive Disease (PD):                               | At least a 20% increase in the sum of the diameters |
| of target lesions, taking as reference the smallest     |                                                     |
| sum on study (this includes the baseline sum if that    |                                                     |
| is the smallest on study).  In addition to the relative |                                                     |
| increase of 20%, the sum must also demonstrate an       |                                                     |
| absolute increase of at least 5 mm. (Note: the          |                                                     |  
CAN-203  
| appearance of one or more new lesions is also      |
|----------------------------------------------------|
| considered progressions).                          |
| Neither sufficient shrinkage to qualify for PR nor |
| sufficient increase to qualify for PD, taking as   |
| reference the smallest sum diameters while on      |
| study.                                             |  
Stable Disease (SD):
Evaluation of Non-Target Lesions  
| Complete Response (CR):   |
|---------------------------|  
| Disappearance of all non-target lesions and     |
|-------------------------------------------------|
| normalization of tumor marker level.  All lymph |
| nodes must be non-pathological in size (<10 mm  |
| short axis).                                    |  
| Note:  If tumor markers are initially above the upper   |                                                 |
|---------------------------------------------------------|-------------------------------------------------|
| normal limit, they must normalize for a patient to be   |                                                 |
| considered in complete clinical response.               |                                                 |
| Non-CR/Non-PD:                                          | Persistence of one or more non-target lesion(s) |
| and/or maintenance of tumor marker level above the      |                                                 |
| nrmal limits.                                           |                                                 |
| Progressive Disease (PD):                               | Appearance of one or more new lesions and/or    |
| unequivocal progression of existing non-target          |                                                 |
| lesions.  Unequivocal progression should not            |                                                 |
| normally trump target lesion status.  It must be        |                                                 |
| representative of overall disease status change, not a  |                                                 |
| single lesion increase.                                 |                                                 |  
Although a clear progression of "non-target" lesions only is exceptional, the clinical opinion of the investigator should prevail in such circumstances, and the progression status should be confirmed at a later time by the investigator.  
Evaluation of Best Overall Response The best overall response is the best response recorded from the start of the treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the treatment started). The patient's best response assignment will depend on the achievement of both measurement and confirmation criteria.  
CAN-203  
| For Patients with Measurable Disease (i.e., Target Disease)                        |                                                                                 |          |                       |                       |
|------------------------------------------------------------------------------------|---------------------------------------------------------------------------------|----------|-----------------------|-----------------------|
| Best Overall                                                                       |                                                                                 |          |                       |                       |
| Non-                                                                               |                                                                                 |          |                       |                       |
| Target                                                                             | New                                                                             | Overall  | Response when         |                       |
| Target                                                                             |                                                                                 |          |                       |                       |
| Lesions                                                                            | Lesions                                                                         | Response | Confirmation is       |                       |
| Lesions                                                                            | Required*                                                                       |          |                       |                       |
| CR                                                                                 | CR                                                                              | No       | CR                    | > 4 wks. Confirmation |
| CR                                                                                 | Non-                                                                            | No       | PR                    |                       |
| CR/Non-                                                                            |                                                                                 |          |                       |                       |
| PD                                                                                 |                                                                                 |          |                       |                       |
| CR                                                                                 | Not                                                                             | No       | PR                    |                       |
| evaluated                                                                          | >4 wks. Confirmation                                                            |          |                       |                       |
| PR                                                                                 | Non-                                                                            | No       | PR                    |                       |
| CR/Non-                                                                            |                                                                                 |          |                       |                       |
| PD/not                                                                             |                                                                                 |          |                       |                       |
| evaluated                                                                          |                                                                                 |          |                       |                       |
| SD                                                                                 | Non-                                                                            | No       | SD                    | Documented at least   |
| CR/Non-                                                                            | once >4 wks. from                                                               |          |                       |                       |
| PD/not                                                                             | baseline                                                                        |          |                       |                       |
| evaluated                                                                          |                                                                                 |          |                       |                       |
| PD                                                                                 | Any                                                                             | Yes or   | PD                    |                       |
| No                                                                                 |                                                                                 |          |                       |                       |
| Any                                                                                | PD**                                                                            | PD       | no prior SD, PR or CR |                       |
| Yes or                                                                             |                                                                                 |          |                       |                       |
| No                                                                                 |                                                                                 |          |                       |                       |
| Any                                                                                | Any                                                                             | Yes      | PD                    |                       |
| See the RECIST 1.1 manuscript for further details on what is evidence of a         |                                                                                 |          |                       |                       |
| nw lesion.                                                                         |                                                                                 |          |                       |                       |
| ***                                                                                | In exceptional circumstances, unequivocal progression in non-target lesions     |          |                       |                       |
| may be accepted as disease progression.                                            |                                                                                 |          |                       |                       |
| Patients with a global deterioration of health status requiring discontinuation of |                                                                                 |          |                       |                       |
| Note:                                                                              | treatment without objective evidence of disease progression at that time should |          |                       |                       |
| be reported as "symptomatic deterioration." Every effort should be made to         |                                                                                 |          |                       |                       |
| document the objective progression even after discontinuation of treatment.        |                                                                                 |          |                       |                       |
| > 4 weeks confirmation with a range of 28 to 32 days.                              |                                                                                 |          |                       |                       |  
| For Patients with Non-Measurable Disease (i.e., Non-Target Disease)                          |                                                                                       |                  |
|----------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------|------------------|
| Non-Target Lesions                                                                           | New Lesions                                                                           | Overall Response |
| CR                                                                                           | No                                                                                    | CR               |
| Non-CR/non-PD                                                                                | No                                                                                    | Non-CR/non-PD*   |
| Not all evaluated                                                                            | No                                                                                    | not evaluated    |
| Unequivocal PD                                                                               | PD                                                                                    |                  |
| Yes or No                                                                                    |                                                                                       |                  |
| Any                                                                                          | Yes                                                                                   | PD               |
| *                                                                                            | 'Non-CR/non-PD' is preferred over 'stable disease' for non-target disease since SD is |                  |
| increasingly used as an endpoint for assessment of efficacy in some trials so to assign this |                                                                                       |                  |
| category when no lesions can be measured is not advised.                                     |                                                                                       |                  |
recist guidelines version 1.1 measurement
duration of response

Duration of overall response: The duration of overall response is measured from the time measurement criteria are met for CR or PR (whichever is first recorded)
until the first date that recurrent or progressive disease is objectively documented
(taking as reference for progressive disease the smallest measurements recorded since the treatment started).  
The duration of overall CR is measured from the time measurement criteria are first met for CR until the first date that progressive disease is objectively documented. Duration of stable disease: Stable disease is measured from the start of the treatment until the criteria for progression are met, taking as reference the smallest measurements recorded since the treatment started, including the baseline measurements.
recist guidelines version 1.1 measurement
progression-free survival

As a secondary endpoint, Progression-Free Survival (PFS) is defined as the duration of time from start of treatment to time of progression or death, whichever, occurs first.
recist guidelines version 1.1 measurement
tumor response review

As a secondary endpoint, the tumor responses will be reviewed by the Investigators participating in the study.  
No central review of tumor responses is planned for this study.