Deviat ion 3: Baseline assessment > 21 day s before start date of first dose of study treatm ent. Deviat ion 4: Received prohibited conco mitant m edicat ions (including other anticancer agents). Please refer to the CSP section 6.4 for those medicat ions that are detailed as being ‘excluded’ from permitted use during the study . This will be used as a guiding principle for the physician rev iew o f all medicat ions prior to database lock to ident ify those likely have an impact on efficacy . 4.1 Prior treatm ent wi th immune -mediated therapy of any of the fo llowing -Anti-PD-L1 -Anti-PD-1 -Anti-Programmed cell death ligand 2(PD -L2) -Anti-Cytotoxi c T-lymphocy te-associ ated anti gen 4 (CTLA -4) -Antibodies o f chimeric antigen receptor T -cell therapy (CAR -T) or other cell therapies Deviat ion 5: Had non -measurable disease at baseline Deviat ion 6: Had a solitary measurable lesion that was biopsied prior to st udy entry Deviat ion 7: Im aging m odali ties for imaging acquired at baseline and first subsequent scan were not consistent (e.g. bone scan used for baseline, fo llowed by CT scan post baseline) Statistical Analysis Plan Study Code D419EC00001 Edition Number 4.0 Date 19Apr2023 CONFIDENTIAL AND PROPRIETARY 27of 653 PRIMARY AND SECONDAR Y VARIABLES 3.1 Derivation of visit tumor respons es The analysis of the primary endpoint, ORR, and the analyses of the secondary endpoints, PFS, DoR, and DCR, will be based on the site Invest igator assessments using the fo llowing cri teria Table 5 Criteria for Investigator assessments Type of cancer Criteria Solid Tumors SARCOMA and STO RECIST 1.1 (see CSP Appendix E) All RECIST 1.1, whether scheduled or unscheduled, will be included in the calculat ions. This is also regardless of whether a patient discont inues study treatm ent or receives another anticancer therapy . Baseline will be assessed within the 21 day s prior to first dose of study treatment and ideally as close as possible to the start of study treatm ent.Assessments are performed eve ry 8 weeks (relative to the date of first dose of study treatm ent) in the first instance. For pati ents who achieve an object ive response or stable disease, and for whom the response is st ill evident at 12 m onths, subsequent tumor assessments are to occur e very 16 weeks ± 1 week until disease progression. If an unscheduled assessment is performed, and the patient has not progressed, every attempt shoul d be made to perform the subsequent assessments at their scheduled visit s. This schedule is to be followed i n order to minimise any unintenti onal bias caused by som e patients being assessed at a different frequency than other pati ents. 3.1.1 Derivation of RECIST 1.1 visit responses For all patients with so lid tumors excluding NB (SARC -1, SARC -2 and STO (dose -finding), SARCOMA and STO (dose -expansio n)), the RECIST tumor response data will be used to determine each patient’s visit response according to RECIST 1.1. It will also be used to determine if and when a pat ient has progressed in accordance with RECIST 1.1 and the ir BoR to study treatm ent. From the Investi gator’s review of the imaging scans, the RECIST tumor response data will be used to determine each pat ient’s visit response according to RECIST 1.1. At each visit, patients will be programmat ically assigned a RECI ST 1.1 vi sit response of com plete response (CR), parti al response (PR), stable disease (SD), or PD, using the informat ion from target Statistical Analysis Plan Study Code D419EC00001 Edition Number 4.0 Date 19Apr2023 CONFIDENTIAL AND PROPRIETARY 28of 65lesions (TLs), non -target lesio ns (NTLs) and new lesio ns and depending on the status of their disease co mpared with baseli ne and previ ous assessments. If a patient has had a tumor assessment that cannot be evaluated then the patient will be assigned a visit response of NE, (unless there is evidence of progression in which case the response will be assigned as PD). RECIST ou tcomes (i.e. PFS, ORR etc.) will be calculated programmat ically for the site Invest igator data (see Section 3.2) from the overall visit responses. 3.1.1.1 Target lesions (TLs) – site Investigator data Measurable disease is defined as having at least one measurable lesio n, not previously irradi ated, which is ≥ 10 mm in the lo ngest diameter (LD), (except lymph nodes which must have short axis ≥ 15 mm) wit h CT or magnet ic resonance imaging (MRI) and which is suitable for accurate repeated measurements. A patient can have a maximum of 5 measurable lesions recorded at baseline with a maximum of 2 lesio ns per organ (representative of all lesions involved and suita ble for accurate repeated measurement) and these are referred to as TLs. If more than one baseline scan is recorded, then measurements from the one that is closest and pri or to fi rst dose will be used to define the baseline sum of TLs. It may be the case t hat, on occasion, the largest lesio n does not lend itself to reproducible measurement. In which circumstance the next largest lesio n, which can be measured reproducibly, should be selected. All other lesio ns (or sites of disease) not recorded as TL should be ident ified as NTLs at baseline. Measurements are not required for these lesio ns, but their status should be fo llowed at subsequent visits. Note: F or pati ents who do not have measurable disease at entry (i.e. no TLs) but have non - measurable disease, ev aluat ion of overall visit responses will be based on the overall NTL assessment and the absence/presence of new lesio ns (see Section 3.1.1.3 for further details). If a pati ent does not have measurable disease at baseline, then the TL visit response will be not applicable (NA). Statistical Analysis Plan Study Code D419EC00001 Edition Number 4.0 Date 19Apr2023 CONFIDENTIAL AND PROPRIETARY 29of 65Table 6 TL Visit Responses (RECIST 1.1) Visit ResponseDescription CR Disappearance of all TLs. Any pathol ogical lymph nodes sel ected as TLs must have a reduction in short axis to <10 mm. PR At least a 30% decrease in the sum of diameters of TLs, taking as reference the baseline sum of diameters as long as criteria for PD are not met. SD Neither sufficient decrease in sum o f diameters to qualify for PR nor sufficient increase to qualify for PD. PD A ≥ 20% increase in the sum of diameters of TLs and an abso lute increase of ≥ 5mm, taking as reference the smallest previous sum of diameters since treatm ent started including the baseline sum o f diameters. NE Only relevant if any of the TLs were not assessed or NE or had a lesio n intervent ion at this visit. Note: If the sum of diameters meets the progressive disease criteria, progressive disease overrides NE as a TL response. NA No TLs are recorded at baseline. CR Complete response; PD Progressive d isease; PR Partial response; SD Stable disease; NA Not applicable; NE Not estimable. Rounding of TL data For calculat ion of PD and PR for TLs percentage changes from baseline and previous minimum should be rounded to one decimal place before assigning a T L response. For example, 19.95% should be rounded to 20.0% but 19.94% should be rounded to 19.9%. Missing TL data If all TL measurements are missing then the TL visit response is NE. Overall visit response will also be NE, unless there is a progression of non-TLs or new lesio ns, in which case the response will be PD. Lymph nodes For lymph nodes, if the size reduces to < 10 mm then these are considered non -patho logical. However, a size will st ill be given, and this size should st ill be used to determine the TL visit response as normal. In the special case where all lymph nodes are < 10 mm and all other TLs Statistical Analysis Plan Study Code D419EC00001 Edition Number 4.0 Date 19Apr2023 CONFIDENTIAL AND PROPRIETARY 30of 65are 0mm then although the sum may be > 0 mm the calculat ion of TL response should be over-written as a CR. TL visit responses subsequent to CR A CR can onl y be followed by CR, PD or NE. If a CR has occurred, then the following rules at the subsequent visits must be applied: Step 1: If all lesions meet the CR criteria (i.e. 0mm or < 10mm for lymph nodes) then response will be set to CR irrespect ive of whether the criteria for PD of TL is also met i.e. if a lymph node LD increases by 20% but remains < 10mm. Step 2: If so me lesio n measurements are missing but all other lesions meet the CR criteria (i.e. 0mm or < 10mm for lymph nodes) then response will be set to NE irrespect ive of whether, when referencing the sum o f TL di ameters, the cri teria for PD are also met. Step 3: If not all lesio ns meet the CR criteria and the sum of lesio ns m eets the cri teria for PD then response will be set to PD. Step 4: If after step s 1 –3 a response can st ill not be determined the response will be set to rem ain as CR. TL too big to measure If a TL beco mes too bi g to m easure this should be indicated in the database and a size (‘x’) above which it cannot be accurately measured shoul dbe recorded. If using a value o f x in the calculat ion of TL response would not give an overall visit response of PD, then this will be flagged and reviewed by the study team blinded to treatment assignment. It is expected that a visit response of PD will remain in the vast majorit y of cases. TL too small to measure If a TL beco mes too sm all to m easure, then thi s will be indicated as such on the eCRF and a value of 5mm will be entered into the database and used in TL calculat ions. However, a smaller value m ay be used if the radiologist has not indicated ‘too small to measure’ on the eCRF and has entered a smaller value that can be reliably measured. If a TL response of PD resul ts, then thi s will be reviewed by the study team . Irradiated lesions/lesion interv ention Previously irradiated l esions (i.e. lesion irradiated pri or to entry into the study ) shoul d be recorded as NTLs and should not form part of the TL assessment. Any TL (including lymph nodes), which has had intervent ion during the study (for exam ple, irradi ation / palliat ive surgery / embo lization), should be handled in the fo llowing way and Statistical Analysis Plan Study Code D419EC00001 Edition Number 4.0 Date 19Apr2023 CONFIDENTIAL AND PROPRIETARY 31of 65once a lesio n has had intervent ion then it should be treated as having intervent ion for the remainder of the study noting that an intervent ion will mo st likely shrink the size of tumors: Step 1: the diameters of the TLs (including the lesions that have had intervent ion) will be summed and the calculation will be performed in the usual manner. If the visit response is PD, thi s will remain as a valid response category . Step 2: If there was no evidence of progression after step 1, treat the lesio n diameter (for those lesions wi th interventi on) as missing and if ≤ 1/3 of the TLs have missing measurements then scale up as described in the ‘Scaling’ sect ion below. If the s caling resul ts in a visit response of PD then the patient would be assigned a TL response of PD. Step 3: If, after both steps, PD has not been assigned, then, if appropriate (i.e. if ≤ 1/3 of the TLs have missing measurements), the scaled sum of diameters calculated in step 2 shoul d be used, and PR or SD then assigned as the visit response. Patients with intervent ion are evaluable for CR as long as all non -intervened l esions are 0 (or <10mm for lymph nodes) and the lesions that have been subject to interven tion have a value of 0 (or <10mm for lymph nodes) recorded. If scaling up is not appropriate due to too few non-missing measurements, then the visit response will be set as NE. At subsequent visit s, the above steps will be repeated to determine the TL and overall visit response. When calculat ing the previous minimum, lesions with intervention should be treated as missing and scaled up (as per step 2 above). Scaling (applicable only for irradiated lesions/lesion intervention) If > 1/3 of TL measurements are missing (because of intervent ion) then the TL response will be NE, unless the sum o f diameters of non -missing TL would result in PD (i.e. if using a value of 0 for missing lesio ns, the sum of diameters has still increased by 20% or more com pared to nadir and the sum o f TLs has increased by ≥5mm from nadir). If ≤ 1/3 of the TL measurements are missing (because of intervent ion) then the results will be scaled up (based on the sizes at the nadir visit to give an est imated sum o f diameters and this will be used in calculat ions; this is equivalent to comparing the visit sum o f diameters of the non-missing lesio ns to the nadir sum o f diameters excluding the lesio ns with missing measurements. Statistical Analysis Plan Study Code D419EC00001 Edition Number 4.0 Date 19Apr2023 CONFIDENTIAL AND PROPRIETARY 32of 65Example of scaling Lesion Longest diam eter at nadir visitLongest diameter at follow - up visit 1 2 3 4 57.2 6.7 4.3 8.6 2.57.1 6.4 4.0 8.5 Intervention Sum 29.3 26 Lesio n 5 is missing at the follow -up visit ; there was a baseline TL sum o f 29.3cm . The sum o f lesions 1-4 at the fo llow-up is 26 cm . The sum of the corresponding lesio ns at the nadir visit is 26.8 cm. Scale up as follows to give an est imated TL sum of 28.4cm: 26/26.8 ×29.3 =28.4 CR will not be allowed as a TL response for visits wher e there i s missing data. Only PR, SD or PD (or NE) could be assigned as the TL visit response in these cases. However, for visits with <1/3 lesion assessments not recorded, the scaled -up sum of TLs di ameters will be included when defining the nadir value f or the assessment of progression. Lesions that split in two If a TL split s in two, then the LDs of the split lesio ns should be summed and reported as the LD for the lesio n that split. Lesions that merge If two TLs merge, then the LD of the merged lesio n shoul d be recorded for one of the TL sizes and the other TL size should be recorded as 0cm. Change in method of assessment of TLs CT, MRI, and clinical examinat ion are the only methods of assessment that can be used wit hin a trial, wi th CT and MRI being the preferred methods and clinical examinat ion only used in special cases. If a change in method of assessment occurs, between CT and MRI this will be considered acceptable and no adjust ment within the programming is needed. Statistical Analysis Plan Study Code D419EC00001 Edition Number 4.0 Date 19Apr2023 CONFIDENTIAL AND PROPRIETARY 33of 65If a change in method invo lves clinical examinat ion (e.g. CT changes to clinical examinat ion or vice versa), any affected lesio ns should be treated as missing. The TL visit response may still be evaluable if the number of missing TL measurements at a visit is ≤1/3 of the total number of TLs. 3.1.1.2 Non-target lesions (NTLs) and new lesions –site Investigator data. At each visit, the Investigator should record an overall assessment of the NTL response. This section provi des the definit ions of the criteria used to determine and record overall re sponse for NTL at the i nvest igational site at each visit. NTL response will be derived based on the Invest igator’s overall assessment of NTLs as follows Table 7 NTL Visit Responses (RECIST 1.1) Visit Responses Descriptio n CR Disappearance of all NTLs present at baseline with all lymph nodes non -patho logical in size (<10 mm short axis). PD Unequivocal progression of exist ing NTLs. Unequivocal progression may be due to an important progression in one lesio n only or in several lesions. In all cases, the progression MUST be clinically significant for the physician to consi der changing (or stopp ing) therapy. Non-CR/Non -PD Persi stence of one or more NTLs with no evidence of progression. NE Only relevant when one or some of the NTLs were not assessed and, in the Invest igator's opinio n, they are not abl e to provi de an evaluable overall NTL assessment at this visit. Note: F or pati ents wi thout TLs at baseline, this is relevant if any of the NTL s were not assessed at this visit and the progression criteria have not been met. NA Only relevant if there are no NTLs at baseline. CR Complete response; NTL Non -target lesion; PD Progressive disease; PR Partial response; SD Stable disease; TL Target lesions; NA Not applicable; NE Not estimable. Statistical Analysis Plan Study Code D419EC00001 Edition Number 4.0 Date 19Apr2023 CONFIDENTIAL AND PROPRIETARY 34of 65To achieve ‘unequivocal progression’ on the basis of NTLs, there must be an overall level o f substant ial worsening in non -target disease such that, even in the presence of SD or PR in TLs, the overall tumor bur den has increased sufficient ly to merit a determinat ion of disease progression. A modest ‘increase’ in the size of one or more NTLs is usually not sufficient to qualify for unequivocal progression status. Details o f any new lesio ns will also be recorded wi th the date of assessment. The presence of one or m ore new l esions is assessed as progression. A lesio n identified at a follow up assessment in an anatomical locat ion that was not scanned at baseline is considered a new lesio n and will indicate disease pro gression. The finding of a new lesio n shoul d be unequivocal: i.e. not attributable to differences in scanning technique, change in imaging modalit y or findings thought to represent something other than tumor. New l esions will be i dentified via a Yes/No tick box. The absence and presence o f new lesio ns at each visit should be listed alongside the TL and NTL visit responses. A new lesio n indicates progression, so the overall visit response will be PD irrespective of the TL and NTL response. If the quest ion‘Any new lesio ns since baseline’ has not been answered with Yes or No and the new lesio n details are blank this is not evidence that no new lesio ns are present but should not overtly affect the derivat ion. Symptom atic progression is not a descriptor for progression of NTLs: it is a reason for stopping study therapy and will not be included in any assessment of NTLs. Patients wi th ‘symptom atic progression’ requiring discontinuat ion of treatm ent wi thout objective evidence of disease progression at that time shoul d continue to undergo tumor assessments where possible unt il objective disease progression is observed. 3.1.1.3 Overall visit response – site Investigator data Table 8defines how the previously defined TL and NTL visit responses will be co mbined with new l esion inform ation to give an overall visit response. Statistical Analysis Plan Study Code D419EC00001 Edition Number 4.0 Date 19Apr2023 CONFIDENTIAL AND PROPRIETARY 35of 65Table 8 Overal l visit responses TARGET NON -TARGET NEW LESIONS OVERALL VISIT RESPONSE CR CR or NA No (or NE) CR CR Non-CR/Non -PD or NE No (or NE) PR PR Non-PD or NE or NA No (or NE) PR SD Non-PD or NE or NA No (or NE) SD PD Any Any PD Any PD Any PD Any Any Yes PD NE Non-PD or NE or NA No (or NE) NE NA CR No (or NE) CR NA Non-CR/Non -PD No (or NE) SD NA NE No (or NE) NE NA NA No (or NE) NED CR Complete response; PD Progressive disease; PR Partial response; SD Stable disease; NA Not applicable; NE Not estimable; NED No evidence of disease. 3.2 Efficacy Variables 3.2.1 Objective response rate (ORR) ORR (per RECIST 1.1, using Investigator assessments) is defined as the percentage of patients wi th at least 1 i nvest igator -assessed visit response of CR or PR that is subsequent ly confirmed on another scan not less than 4 weeks after visit observed response. Data ob tained up until progression, or the last evaluable assessment in the absence of progression, will be included in t he assessment of ORR. Patients who go off treatment without progression, receive a subsequent therapy , and then respond will not be included as responders in the ORR. ORR is primary endpoint of dose -expansion phase. 3.2.2 Progression -free survival (PFS) Progression free survival (per RECIST 1.1, as assessed by the si te Investi gator) will be defined as the time fro m the date of first dose of study treatm ent unt il the date of objective disease progressi on or death (by any cause in the absence of progression ) regardl ess of Statistical Analysis Plan Study Code D419EC00001 Edition Number 4.0 Date 19Apr2023 CONFIDENTIAL AND PROPRIETARY 36of 65whether the patient withdraws fro m study therapy or receives another ant i-cancer therapy prior to progression (i.e. date of PFS event or censoring –date of first dose + 1). Patients who have not progressed or died at the time of analysis w ill be censored at the time of the latest date of assessment fro m their last evaluable RECIST 1.1 assessment. However, if the pat ient progresses or dies after 2 or more missed visit s, the patient will be censored at the time of the latest evaluable (RECIST 1.1)assessment prior to the 2 missed visits (Note: NE vi sit is not considered a missed visit) . Given the scheduled visit assessment scheme (i.e. eight -weekly (+/ -1 week) for the first 12 months with the opti on of moving to every 16 weeks ± 1 week thereafter (for those with a sustained object ive response), unt il clinical progressio n/deterioration ) the definit ion of 2 missed visits will change over time on a per pati ent basis . If the previous (RECIST 1.1) assessment is between study day 49 (i.e. we ek 7) and less than the last assessment on an 8 -weekly schedule then two missed visit s will equate to 18 weeks since the previous RECIST 1.1 assessment, allowing for early and late visit s (i.e. 2 x 8 weeks + 1 week for an early assessment + 1 week for a la te assessment = 18 weeks). If the two missed visits occur over the period when the scheduled frequency o f RECIST 1.1 assessments changes fro m eight-weekly to sixteen -weekly this will equate to 26 weeks (i.e. take the average o f 8 and 16 weeks which gives 1 2 weeks and then apply same rationale, hence 2 x 12 weeks + 1 week for an early assessment + 1 week for a late assessment = 26 weeks). Once the scheduling changes to sixteen -weekly assessments, two missing visit s will equate to 34 weeks (i.e. 2 x 16 weeks + 1 week for an early assessment + 1 week for a late assessment = 34 weeks). If a patient has no evaluable visits or does not have baseline data, they will be censored at day 1 unless they die within 2 visits o f baseline (16 weeks plus 1 week allo wing for a late assessment within the visit window) then they will be treated as an event with date of death as the event date. The PFS time will always be derived based on scan/assessment dates not visit dates. RECIST 1.1 assessments/scans contributing towards a particular visit may be performed on different dates. The fo llowing rul es will be applied: For Invest igator assessments, date of progression will be determined based on the earliest of the assessment/scan dates of the component that triggered the progressio n. When censoring a patient for PFS the patient will be censored at the latest of the dates contributing to a particular overall visit assessment. Statistical Analysis Plan Study Code D419EC00001 Edition Number 4.0 Date 19Apr2023 CONFIDENTIAL AND PROPRIETARY 37of 65Note: F or TLs, only the latest scan date i s recorded out of all scans performed at that assessment for the T Ls and similarly for NTLs, only the latest scan date is recorded out of all scans performed at that assessment for the NTLs. 3.2.3 Overall Survival (OS) OS is defined as the time fro m the date of first dose of study treatment until death due to any cause regardl ess of whether the patient withdraws fro m study treatm ent or receives another anti-cancer therapy (i.e. date of death or censoring – date of first dose + 1). Any patient not known to have died at the time o f analysis will be censored based on the last reco rded date on which the patient was known to be alive. (‘Date subject confirmed to be alive’, recorded within the SURVIVE m odule of the eCRF). Note: Survival calls will be made fo llowing the date of data cut off (DCO) for the analysis (these contacts should generally occur wi thin 7 days of the DCO) and if pat ients are confirmed to be alive or if the death date is post the DCO date, these patients will be censored at the date of DCO. The status of ongoing, withdrawn (from the study ) and “l ost to f ollow-up” pa tients at the time o f the final OS analysis should be obtained by the site personnel by checking the patient’s notes, hospital records, contacting the patient’s general pract itioner and checking publicly -available death registries. In the event that the pa tient has act ively wit hdrawn consent to the processing of their personal data, the vital status of the patient can be obtained by site personnel fro m publicly available resources where it is possible to do so under applicable local laws. Note that for any OS analysis performed prior to the final OS analysis, in the absence o f survival calls being made, it may be necessary to use all relevant eCRF fields to determine the last recorded date on which the patient was known to be alive for those patients still on treatm ent. The l ast date for each individual pat ient is defined as the latest among the fo llowing dates recorded on the eCRF: AE start and stop dates Admissio n and discharge dates of hospitalizat ion Study treatm ent date End of treatment date Laboratory test dates Date of vital signs Date of ECG Statistical Analysis Plan Study Code D419EC00001 Edition Number 4.0 Date 19Apr2023 CONFIDENTIAL AND PROPRIETARY 38of 65Disease assessment dates on RECIST/non -RECIST eCRF Start and stop dates of alternat ive ant icancer treatment Date l ast known alive on survival status eCRF End of study date Date of any other safet y data If a patient i s known to have died where only a parti al death date i s available, then the date of death will be imputed as the latest of the last date known to be alive +1 from the database and the death date using the available information provided: a.For Missi ng day only –using the 1stof the m onth b.For Missing day and Month –using the 1st of January If there is evidence of death but the date is ent irely missing, it will be treated as missing, i.e. censored at the last known alive date. 3.2.4 Duration of response (DoR) DoR (per RECIST 1.1, using Invest igator assessment) will be calculated for all patients with a confirmed overall response of CR or PR, and will be defined as the time from the date of first docum ented response (which is subsequently confirmed) unt il the first date of documented progression or death in the absence of disease progressio n (i.e. date of PFS event or censoring –date of first response + 1). The end of response should coincide with the date of progression or death from any cause used for th e (RECIST 1.1) PFS endpoint. The time of the init ial response will be defined as the latest of the dates contribut ing towards the first visit response of PR or CR that was subsequent ly confirmed. If a patient does not progress following a response, then their DoR will be censored at the PFS censoring t ime. DoR will not be defined for those patients who do not have documented response. 3.2.5 Best objective response (BoR) BoR is calculated based on the overall visit responses fro m each (RECIST 1.1, using Invest igator assessment) assessment. It is the best response a patient has had during their t ime in the study , but pri or to starting any subsequent cancer therapy and up unt il (RECIST 1.1) progression or the last evaluable assessment in the absence of (RECIST 1.1) progression. Categorization of BoR for solid tumors will be based on RECIST 1.1 using the fo llowing response categories: CR, PR, SD, PD, and NE. Statistical Analysis Plan Study Code D419EC00001 Edition Number 4.0 Date 19Apr2023 CONFIDENTIAL AND PROPRIETARY 39of 65CR or PR must be confirmed (confirmed is defined as 2 consecut ive assessments with the same outcome, not less than 4 weeks apart). BoR will be determined programmat ically (based on RECIST 1.1) using all Invest igator assessments up until the first progression event. For patients whose progressi on event i s death, BoR will be calculated based upon all evaluable (REC IST 1.1) assessments prior to death. For pati ents who die wi th no evaluable (RECIST 1.1) assessments, if the death occurs ≤119 days (i .e. 2 × 8 weeks + 7 day s) after first dose of study treatm ent, then BoR will be assigned to the progression (PD) category .For pati ents who die wi th no evaluable (RECIST 1.1) assessments, if the death occurs >119 day s (i.e. 2 × 8 weeks + 7 day s) after the date of first dose of study treatm ent, then BoR will be assigned to the NE category . Progression events that have been censored due to them being >119 day s after the last evaluable assessment will not con tribute to the BoR derivat ion. 3.2.6 Disease control rate (DCR) DCR at 16 or 24 weeks will be defined as the proportion of patients who achieve a BoR of unconfirmed CR or PR, re spectively, or who have SD (without subsequent cancer therapy ) for at least 16 weeks − 7 day s or 24 weeks -7 day s, respect ively, after start of treatment. For NB, MR will be included in the DCR count. DCR will be determined programmat ically (based on REC IST 1.1, using Invest igator assessment) from the overall visit response using all data up until the first progression event . 3.2.7 Proportion alive and progression free at 12 (APF12) and 18 (APF18) months APF12 will be defined as the Kaplan -Meier (KM) estimate o f PFS (per RECIST 1.1, using Invest igator assessment ) at 12 m onths. Similarly , APF18 will be defined as KM est imate of PFS at 18 months. 3.2.8 Overall survival at 12 (OS12) and 24 (OS24) months OS12 will be defined as the KM est imate of OS at 12 months. Similarl y, OS24 will be defined as the KM est imate of OS at 24 months. 3.3 Safety Variables Safety and tol erabilit y will be assessed in term s of AEs (including serious adverse events [SAEs]), deaths, laboratory data, vi tal signs, ECGs, phy sical examinat ions and exposure. These will be co llected for all pat ients. Statistical Analysis Plan Study Code D419EC00001 Edition Number 4.0 Date 19Apr2023 CONFIDENTIAL AND PROPRIETARY 40of 65The Safet y analysis set (SAS) will be used for reporting o f safety data. On-treatm ent is defined as assessment where the date and time of the assessment is the same as or greater than the date and time of first treatment with eit her trem elimumab or durvalumab and up to (and including) 90 day s after the l ast dose date of tremelimumab or durvalumab. For vital signs, On -treatm ent is defined as assessment where the date of first treatment with eit her tremelimu mab or durval umab and update (i ncluding) 30 day s after the l ast dose date of tremelimumab or durvalumab. 3.3.1 Adverse Events AEs will be assigned to the fo llowing peri ods related to date and time of onset of the AEs relative to first and last dose dates of stud y treatm ent and the date of starting any subsequent anti-cancer therapy post -discont inuat ion of study treatm ent. AE occurrence Period Assigned Date before first treatment with eit her durvalumab or tremelimumab Pre-treatm ent Date the same as or greater than the date of first treatment with durvalumab or tremelimumab, either as monotherapy or combinat ion therapy (or date before first treatment, but worsening following first dose) and u p to (and including) 90 days after the last dose date of durvalumab or tremelimumab, or init iation of the first subsequent anti-cancer therapy following discont inuat ion of study treatm ent (whichever occurs first)On-treatm ent, prior to subsequent ant i- cancer therapy Date the same as or greater than the date of first treatmen t with durvalumab or tremelimumab, either as monotherapy or combinat ion therapy (or date before first treatment, but worsening following first dose) and u p to (and including) 90 days after the last dose date of durvalumab or tremelimumabOn-treatm ent Date afterinitiation o f the first subsequent anti -cancer therapy following discont inuat ion of study treatment up to (and including) 90 days after the last dose date of durvalumab or tremelimumabOn-treatm ent Post-subsequent anti-cancer therapy Date m ore tha n 90 days after the last dose date of eit her durvalumab or trem elimumab Post-study treatm ent AE Adverse event. AEs that have missing causalit y (after data querying) will be assumed to be related to study treatm ent.