Several cases of local reactions of erythema and induration have been reported and more recently four patients experienced allergic reactions related to TG01 or TG01/GMCSF . Two of them experienced a serious adv erse event of anaphylaxis soon after TG01 administration considered to be related to the GM-CSF/TG01 injections or TG01 alone . The third patient experienced on 2 occasions symptoms of an allergic reaction approximately 10 min after injections ( GM-CSF/TG01 ). The last patient experienced dizziness, lightheaded, puffiness of both eyes following GM-CSF/ TG01 before starting gemcitabine treatment . The mechanism for the anaphylactic reactions occurring so long after the start of vaccination, but following the cour se of gemcitabine, and its similarity to the two other cases where gemcitabine has been given for at least 3 -4 cycles, might suggest some association as yet unexplained. In addition flu- like symptoms (including fever), headaches, urticaria and oedema may occur. Back pain, nausea and diarrhoea have also been reported as treatment related and there were 2 related serious adverse events of arthritis and hypoglycaemia. It is difficult to dissociate abnormal (Grade 3/4) laboratory toxicities from the patients’ underlying disease or medications and in study 98010, which uses all of the peptides of TG01, there were 3 events of granulocytopaenia, raised alkaline phosphatase and raised gamma -GT. However, there were only 13 patients in this category so carefully monitoring of haematology and biochemistry is required. CT TG01 -01 Version v 10.0 27 June 2018 Confidential 57 / 87 GM-CSF is generally well tolerated and, with the low dose anticipated may have few if any adverse reactions. However, in previous studies the most common adverse events are: transient myalgia, weakness, mild fatigue, rashes, and mild erythema at the site of injection. Gemcitabine : Most frequent toxicities reported with gemcitabine given as single agent are myelosuppression, nausea and vomiting, transient elevations of one or both serum transaminases, pro teinuria and haematuria and a few cases of haemolytic uraemic syndrome (HUS), f ever frequently associated with other flu- like symptoms, r ash, dyspnoea, oedema , flu-like symptoms with or without fever , infection, alopecia and paresth aesias. 5-FU: most frequent toxicities reported with 5 -FU are stomatitis , oesopharyngitis , diarrh oea, anorexia, nausea and emesis, alopecia, dermatitis and leucopenia. Leucovorin : most frequent toxicities reported with Leucovorin are diarrhoea, stomatitis , myelosupression, skin rash, hives, pruritus and wheezing (although rare). 4.5.2 Chemotherapy dose interruption/reduction Gemcitabine Institutions should follow the manufacturer’s instructions for dosing modification for the country in which the study is being conducted.