Section 5.1 (Inclusion criteria): Reference to hepatic metastasis alanine aminotransferase and aspartate aminotransferase limits for patients with hepatic metastases has been removed as patients are required to have non-metastatic disease. Section 5.1 and 5.2 (Eligibility criteria): Eligibility criteria have been updated to allow gemcitabine in combination with cisplatin or carboplatin as a prior sCRT treatment, provided there is no overlap between chemotherapy and radiation. Section 8.2.1 (Haematology safety laboratory assessments): Clarification of language related to coagulation testing at baseline on Day 1. Section 8.4.5.1 (Toxicity management related to durvalumab) and Appendix G: Section has been updated to reflect that Toxicity Management Guidelines (TMGs) are now provided as an Annex to the Protocol. Appendix G has been removed.

Section 1.1 (Synopsis), Section 1.2, Table 1 (SoA), Section 1.3 (Figure 1), Section 4.1 (Overall Design), Section 4.1 (Overall Design) Figure 2, Section 4.2.5 (Timing of treatment with durvalumab (MEDI4736) relative to sequential chemoradiation therapy), Section 5.1 (Inclusion Criteria), Section 9.2 (Sample Size Determination) Table 13: The time window from end of sCRT to first dose of IP was extended from 28 to 42 days. Section 1.2, Table 1, Footnote l (SoA): The frequency of on study pregnancy testing was changed from “every 4 weeks” to “prior to every dosing visit (within 3 calendar days prior to dosing in line with other laboratory tests)”. Section 5.1 (Inclusion Criterion 7): Inclusion criterion 7 was amended to supplement guidance on acceptable baseline imaging. It was added that assessment of tumour response should be performed based on the latest scan performed per physician assessment/criteria). If the patient has an intermediate scan between chemotherapy and radiotherapy, this scan should be used as baseline scan provided it fulfils the RECIST-defined CT imaging acquisition parameters. Section 5.2 (Exclusion Criterion 11, option (a)): It was added to exclusion criterion 11 that patients with ≥Grade 2 lymphopenia will be evaluated on a case-by-case basis after consultation with the Study Physician. Section 8.2.2 (Physical Examination): Clarification was made that targeted physical examinations during the treatment cycles are not expected in asymptomatic patients. Section 8.2.3 (Vital Signs): Clarification that respiratory rate and temperature measurements are part of the vital signs assessments. Section 9.2 (Sample Size Determination): The sample size per cohort was changed: WHO/ECOG PS 0 to 1 cohort from 120 to 100-120 patients and WHO/ECOG PS 2 cohort from 30 to up to 30, depending on recruitment.

Section 1.1 (Synopsis), Section 3 (Study objectives), Table 3 footnote: It was clarified that TRAEs and PRAEs are used interchangeably and PRAEs will be reported in the SAP, Tables, Figures, and Listings, and CSR Section 1.1 (Synopsis, Treatments and treatment duration), Section 4.1 (Overall design, Figure 2), and Section 6.1.2 (Dose and treatment regimens): It was clarified that treatment for up to a maximum of 24 months is referring to a maximum of 24 months from Cycle 1 Day 1. Section 4.1 (Overall design, Investigational product, dosage and mode of administration): It was clarified that treatment is for a maximum of 24 months from Cycle 1 Day 1. Section 6.1.1 (Investigational product, Preparation of durvalumab (MEDI4736) doses for administration with an IV bag) and Section 8.2.3 (Vital signs): A time window of ±10 minutes for the durvalumab infusion time was added based on latest AstraZeneca durvalumab protocol template. Section 6.1.3 (Treatment after the end of the study, Treatment after final overall survival data cut-off): The misleading sentence that no OS data will be recorded in the study database after DCO was deleted and it was clarified that in this section the DCO is referring to the final DCO Section 8.3.13 (Safety data to be collected following the final data cut-off of the study): It was clarified that in this section the DCO is referring to the final DCO. Section 8.4.1 (Reporting of serious adverse events): The guidance on how to proceed if the WBDC system is unavailable was updated to match the safety handling plan. Section 8.4.5.1 (Specific toxicity management and dose modification information – Durvalumab and durvalumab + tremelimumab): The reference to the website containing the current Dosing Modification and Toxicity Management Guidelines was removed.