V1 to v 2: Protocol version number and date updated to Version 2 date 08/11/2011 in the document header, title page and protocol signature page; Change study acronym from FGF-R to FGFR in the header and page 2;Change study acronym from FGFR to FGFR; Page numbers updated in the table of contents; Addition of heading Appendix B – Summary of protocol changes to the table of contents; Removal of abstinence as an acceptable method of contraception for this study; Change Echo/MUGA scan to Echo/MUGA Scan;Correction of schedule of assessment for MUGA/Echo scan in Table 2 – change to C2D1 from C1D1;Addition of details regarding MUGA/Echo scan: A MUGA scan or echocardiogram to assess left ventricular ejection fraction (LVEF) will be conducted at screening and on day 1 of Cycle 2 (± 1 week) and 3-monthly thereafter until discontinuation of study treatment;Replace ‘Table 1’ with ‘Table 2’; Addition of Appendix B, Summary of Protocol changes. PISCF changes: Removal of abstinence as a method of contraception, clarification of the ECHO/MUGA scanning schedule and correction of typo errors.

Prot v2 - v3: Removed ‘effective date’ ‘review date’ & protocol reference; Change of Trial Physician to Dr E Smyth;Insertion of ‘site name’ for protocol sign. page & changed date of protocol version; changed RMH to RM Trust;Change of Trial Stat to C Peckitt; Amended fax no: Addition of exploratory cell culture objective; Addition of data regarding levels of FGFR amplification & relationship to response to FGFR inhibition; Clarification of results of mutagenicity testing; Data regarding safety of AZD4547 safety & tolerability at 80 mg BD cont. dosing schedule; Removal of genotoxicity as risk due to negative Ames test result; Addition of requirement for 10/16 patients per cohort to have amplification ratio of >=2.8, Removal of limited field radiation within 2 weeks of study entry as exclusion criteria; Change in inclusion criteria to reflect both FGFR amplification and ratio of >=2.0; Stability of brain metastases to be confirmed radiologically prior to study entry; Change in eligibility criteria 5 to allow patients with grade 2 neuropathy; Change in eligibility criteria 15 to allow patients with a history of varicella zoster; Description of 20mg tablets; Change to dosing schedule from 80 mg BD two weeks on one week off to continuous dosing; Update on RPED events referred to investigators brochure; Change in time allowed for resolution of ocular toxicity from 14 to 21 days; Change to dose levels – dose level – 1 now 60mg bd, dose level -2 now 40mg bd; Change toxicity management algorithm to reference figure 4; Changes to guidelines for management of ocular toxicity (Figure 3) provision of separate algorithm (figure 4) for management of asymptomatic RPED; Change eligibility criteria to study, patients must demonstrate FGFR amplification & FGFR ratio of >=2.0; Clarification that PET-CT, biopsy, bone & blood borne biomarker testing is due to eligibility criteria met; Confirmation that data is password protected & data transfer agreement with Quintiles.

Protocol v3 - 4: Version number and date updated throughout; Study period updated; Emerging safety data removed (IB used as reference – see p 57); clinical experience updated. Typos amended. insertion of…. Three of the 34 patients had on treatment SAE’s …..in the same patient the investigator also listed morphine as a suspected medication; Insertion to confirm IB is reference safety source. Addition of ….average tumour size change with AZD 4547 was at BEST comparable with paclitaxel; Study duration updated; Exclusion criteria amended;;Added text “The above toxicity management refers to non-haematological toxicity only. Specifically, at the beginning of each cycle of treatment absolute neutrophil count must be ≥1.5 and Plt≥100 in order to initiate treatment.” Determination of the expectedness of an SAE will be based on the contents of the IB. (amended); Section 12.1 reference to the use of CRF’s as source data; Removal of ‘both’ arms – is a single arm study; Confirmation that CRF’s will be used as source data

Protocol v4 -5: Title corrected to insert CYP3A4 and the word NOT into the following title: Drugs affecting CYP3A4 or CYP2D6 Metabolism that are strongly NOT recommended to be combined with AZD4547; Removed text referring to FISH6 score as this was Quintiles specific; Change in primary endpoint to objective response; Change in eligbility of NSCLC specific cohort, establishment of “basket” cohort for patients with FGFR dysregulated tumours; Each cohort will recruit 9-17 patients dependent on response observed; Addition of copy number variation assessment at prescreening; Change in provision of second biopsy from mandatory to optional but encouraged;Minor formatting changes;Addition of publication of arms separately; Update of clinical data on other AZD4547 studies; Addition of CT one month following response to confirm response; Addition of cholangiocarcinoma translational protocol: Main study PISCF v7, 23.2.15 Pre screening PISCF v4, 23.2.15 GP letter v5, 23.2.15 IB updated v 8 & 9

Protocol v5 - 6 : Removal of breast cohort; includes updated lcinial results from part B of study D2610C00003, alopecia removed from list of expected toxicities; change in age of eligibility from age 25 to age 16 plus for oesteosarcoma pts, clarification of management of ocular toxicity; removal of blood borne biomarker testing for FGFR 23 and BFGF. removed as replaced by lab manual.