Study is Designed to Assess the Safety and Tolerability of AZD4547 at Increasing Doses in Patients With Advanced Tumours

• To investigate the safety and tolerability of AZD4547 when given orally to patients with advanced solid malignancies and define the maximum tolerated dose (MTD). [ Time Frame: Safety Blood samples weekly throughout dosing. Physical Examination every 3 weeks. ECG and vital signs at least every 3 weeks. ]
• To investigate the safety and tolerability of AZD4547 when given orally to patients with advanced solid malignancies and define the maximum tolerated dose (MTD). [ Time Frame: Ophthalmology at baseline and 3 weeks after start of BD dosing. MUGA / Echocardiogram at baseline, 3 weeks after start of BD dosing, and then every 3 months. ]

• To characterise the pharmacokinetics (PK) of AZD4547 following a single administration and at steady state after dosing when given orally. [ Time Frame: PK samples out to 96 hours after single dose (in parts A & B only). Steady state PK profile 3 weeks after the start of BD dosing. ]
• To obtain a preliminary assessment of the anti tumour activity of AZD4547 by evaluation of tumour response using Response Evaluation Criteria in Solid Tumours (RECIST) criteria version 1.1 [ Time Frame: Baseline assessment, then assessment every 6 weeks after start of treatment. ]

• To characterise the pharmacokinetics (PK) of AZD4547 following a single administration and at steady state after multiple dosing when given orally. [ Time Frame: PK samples out to 96 hours after single dose. Staeady State PK profile 3 weeks after start of BD dosing ]
• To obtain a preliminary assessment of the anti-tumour activity of AZD4547 by evaluation of tumour response using Response Evaluation Criteria in Solid Tumours (RECIST) criteria v1.1. [ Time Frame: Baseline assessment, then assessment every 6 weeks after start of treatment. ]

• Cancer
• Advanced Solid Malignancies

• Drug: AZD4547
  Single dose is followed by washout 5-10 days before multiple dose, and at dose of 80mg twice daily
• Drug: AZD4547
  Patients start at a dose of 80 mg twice daily, with no washout
• Drug: AZD4547
  Single dose is followed by washout 5-10 days before multiple dose

• Experimental: Part A
  Ascending doses of AZD4547 administered orally to patients to define the maximum tolerated dose (MTD) and/or a continuous, tolerable Recommended Dose (RD)
  Intervention: Drug: AZD4547
• Experimental: Part B
  Dose expansion phase, at the RD defined in Part A
  Intervention: Drug: AZD4547
• Experimental: Part C
  Expansion phase in patients with FGFR1 and FGFR2 amplified tumours commencing at the RD defined from Part A
  Intervention: Drug: AZD4547

Inclusion Criteria:

• Minimum life expectancy of 12 weeks
• The presence of a solid, malignant tumour that is resistance to standard therapies or for which no standard therapies exist
• In the expansion for the study patients must have a tumour at least 1cm in size that can be measure using a CT or MRI scan, and provide a tumour sample to the sponsor company for testing of FGFR1 and/or 2 amplification
• Expansion, 5 groups of advanced cancer
• Solid tumours,FGFR1 and/or FGFR2 gene amplified
• Squamous NSCLC, FGFR1 gene low & high amplified
• Gastric adenocarcinoma, including the lower oesophagus/gastro-oesophageal junction, FGFR2 gene low & high amplified
• Aged at least 25 years

Exclusion Criteria:

• Treatment with any other chemotherapy, immunotherapy or anticancer agents within 3 weeks before the first dose of study
• An inability to be able to take the study medication
• A bad reaction to AZD4547 or any drugs similar to it in structure or class.