4. 2 A D As T he prese nce of A D A will be assesse d i n ser u m sa m ples f or patie nts wit h s oli d t u m ors. S a m ples will b e meas ure d f or t he prese nce of A D As a n d A D A -ne utralizi n g a nt i b o dies f or b ot h d ur val u ma b a n d tre meli m u ma b usi n g vali date d assa ys. 3. 5 Bi o m ar ker V ari a bles T he f o ll o wi n g e x pl orat or y bi o m ar kers will be c ollecte d C CI Statistical A nal ysis Pla n St u d y C o de D 4 1 9 E C 0 0 0 0 1 E diti o n N u m ber 4. 0 Date 1 9 A pr 2 0 2 3 C O N FI D E N TI A L A N D P R O P RI E T A R Y 4 8 of 6 5 4 A N A L Y SI S M E T H O D S 4. 1 Ge ner al pri nci ples T he pri mar y a nal ysis c ut off will be defi ne d at a p pr o xi matel y 6 m o nt hs after e nr oll me nt of t he last pati e nt. At t his p oi nt, data a nal ysis will be perf or me d, a n d t he C S R will be writte n. After t hi s, pati e nts still i n t he st u d y will c o nt i n ue t o be f oll o we d a n d a C S R a d de n d u m will be iss ue d f or O S a n d safet y data c ollect i o n. F or P K a n d ot her bi o mar kers, t he sa m ple bi oa nal ysis will be perf or me d b y Astra Ze neca or a c o ntracte d l a b or at or y . P K para m eters will b e deri ve d b y La bc or p . T he m er gi n g of P K c o nce ntrati o n data wit h act ual ela pse d t i me fr o m d ose f or P K sa m pli n g ti mes will be perf or m e d b y I Q VI A Pr o gra m mi n g. T he P K s u m maries a n d data list i n gs will be t he res p o nsi bilit y of I Q VI A B i o st ati st ics. Stati st ical s u m maries a n d a nal yses of n o n -P K data will be perf or me d b y I Q VI A u n der t he di rect i o n of t he Bi ostatist ics Gr o u p, Astra Ze neca usi n g S A S ® versi o n 9. 4 or hi g her a n d, w here a p pr o priate, a d dit i o nal vali date d s oft ware. T here i s n o f or m al st ati st ical test i n g f o r t he d ose -fi n di n g p hase of t he st u d y. T he d ose -e x pa nsi o n p hase of t he st u d y will f or m all y test t he f oll o wi n g h y p ot hesis: H 0: O R R ≤ 1 0 % H 1: O R R > 1 0 %. C CI Statistical Analysis Plan Study Code D419EC00001 Edition Number 4.0 Date 19Apr2023 CONFIDENTIAL AND PROPRIETARY 49of 65The test will be done at the 1- sided 5% l evel and it will be performed for the SARCOMA cohort. No formal stati stical testing will be performed for the STO cohort. For the dose -finding phase, and dose -expansio n phase where relevant, dose levels will be labelled in summary tables as: durvalumab xx mg/kg + tremelimumab xx mg/kg with xx depending on the dose levels used. For the dose -expansio n phase, cohorts will be labelled in summary tables as: SARCOMA STO Total columns will be included for the dose -finding and dose -expansio n phases separately for outputs where a total column is requ ired. Visits will be present as cycle and day (e.g.