05FPRF Immune Design Corp. I MDZ -04-1702 SAP Draft V1.0 for Protocol V2.0 Version Date: 2018- 05-25 Confidential 18 / 36 4 SAMPLE SIZE DETERMIN ATION A total of 248 subjects will be randomly assigned in a 1:1 ratio such that 124 subjects will be included in each of the 2 treatment arms. The study is powered at 90% with 179 death events required to detect a HR of 0.59, which corresponds to a 41% reduction in the risk of death, and an approximately 69% increase in median survival compared with a placebo median survival of 20 months, and uses a 1- sided log -rank test, with an alpha of 0.0125, a 1:1 randomization ratio, and an interim OS non- binding futility analysis with boundary of HR = 1.0 at 67% of information time (1 20 death events from the 179 required death events for the final OS analysis). A total of 248 subjects will yield the 179 events required, under the assumption of 24 months for enrollment (25% of subjects enrolled in the first year and 75% of subjects enrolled in the second year) plus 42 additional months of follow -up. With 141 PFS events, the study is powered at 90% to detect a HR of 0.55, which corresponds to a 45% reduction in the risk of PFS events (either disease progression or death), and an approxima tely 82% increase in median PFS compared with a placebo median PFS of 4 months, and uses a 1 -sided log- rank test, with an alpha of 0.0125, and a 1:1 randomization ratio. 5 STUDY ENDPOINTS 5.1 Efficacy Endpoints 5.1.1 Primary Efficacy Endpoint Two primary efficacy endpoints of PFS by investigator’s assessment and OS will be compared between CMB305 and placebo. 5.1.1.1 Progression -free S urvival (PFS) PFS by investigator’s review will be the primary endpoint . PFS by investigator’s assessment is defined as th e time from randomization to the investigator -determined (using RECIST v1.1) date of disease progression or death, whichever comes first : [PFS = investigator -determined PD date or death date – randomization date + 1 ]. Investigator -determined PD event inclu des the following s:  Disease progression per RECIST v1.1  Symptomatic deterioration (global health deterioration) as described by RECIST v1.1  For subjects with NED at time of randomization, any new malignant lesion that occurs after randomization per RECIST v1.1 PFS will be right- censored based on Table 3 for subjects who meet the following conditions : 05FPRF Immune Design Corp. I MDZ -04-1702 SAP Draft V1.0 for Protocol V2.0 Version Date: 2018- 05-25 Confidential 19 / 36 Table 3 : Censoring Rules for PFS Analysis Situation Date of Censoring Outcome No investigator -determined PD or death at the time of study discontinuation Date of last adequate tumor assessment with no evidence of PD on or before study discontinuation Censored Investigator -determined PD or death after 2 or more consecutive missed tumor assessments Date of last adequate tumor assessment with no evidence of PD that is before the first missed assessment Censored Investigator -determined PD or death after the start of subsequent intervention Date of last adequate tumor assessment with no evidence of P D that is before the first subsequent intervention Censored No baseline and/or adequate post baseline tumor assessments or death at time of study discontinuation Date of randomized Censored * Adequate tumor assessment : tumor assessment s with CR, PR, or SD as overall tumor response . PFS by independent radiological review , if required, will be the supportive endpoints and follow similar definition and censorship as PFS by investigator’s assessmen t, except that only PD from independent radiol ogical review will be included as PD ( symptomatic deterioration and clinical PD will not be included as PD) . 5.1.1.2 Overall Survival (OS) OS is defined as the time from randomization to the date of death from any cause: [OS = death date – randomization date + 1 ]. Any subject without a date of death in the database at the time the survival analyses are performed will be censored at the date of last known alive. The date of death is recorded on the death report form page. The last known alive date is defined as the last date th e subject was known to be alive at the study . The last known alive date will be the latest date among the following:  Last assessment date among, e.g., vital signs assessment, performance status assessment, tumor imaging , and assessment date in third -party data such as central laboratory, ECG etc.  Last adverse events date  Last known alive date collected on the ‘ Long -term Follow -up’ page of eCRF  Date of last contact in ‘End of Study ’ page of the eCRF 05FPRF Immune Design Corp. I MDZ -04-1702 SAP Draft V1.0 for Protocol V2.0 Version Date: 2018- 05-25 Confidential 20 / 36  Last date among last study treatment, and last concomitant medications, s ubsequent interventions administered after study treatment discontinuation. 5.1.2 Secondary Efficacy Endpoint s The secondary efficacy endpoints of TTNT, DMFS, ORR and QoL using the EQ -5D-5L or EQ - 5D-Y will be compared between treatment arms. 5.1.2.1 Time to Next Treatment (TTNT) TTNT is defined as the time from randomization to the start of post -study treatment subsequent intervention: [TTNT = start date of subsequent intervention – randomization date + 1 ]. Subsequent intervention includes anticancer therapy , cancer -related surgery and local regional therapy .