Study of AZD5305 as Monotherapy and in Combination With Anti-cancer Agents in Patients With Advanced Solid Malignancies

Prior treatment

• Treatment with any of the following:
  • Nitrosourea or mitomycin C within 6 weeks of the first dose of study treatment
  • Any investigational agents or study drugs from a previous clinical study within 5 half-lives or 3 weeks (whichever is shorter) of the first dose of study treatment
  • Any other chemotherapy, immunotherapy or anticancer agents within 3 weeks of the first dose of study treatment
  • Any live virus or bacterial vaccine within 28 days of the first dose of study treatment
• Concomitant use of medications or herbal supplements known to be cytochrome P450 3A4 (CYP3A4) strong inhibitors or inducers.
• Receiving continuous corticosteroids at a dose of \>10 mg prednisone/day or equivalent for any reason.
• Major surgery within 4 weeks of the first dose of study treatment.
• Radiotherapy with a wide field of radiation within 4 weeks or radiotherapy with a limited field of radiation for palliation within 2 weeks of the first dose of study treatment.
• Spinal cord compression or brain metastases unless asymptomatic, treated and stable and not requiring continuous corticosteroids at a dose of \>10mg prednisone/day or equivalent for at least 4 weeks prior to start of study treatment. Patients with leptomeningeal carcinomatosis are excluded.
• Other cardiovascular diseases as defined by any of the following:
  • Symptomatic heart failure,
  • uncontrolled hypertension,
  • hypertensive heart disease with significant left ventricular hypertrophy
  • acute coronary syndrome (ACS)/acute myocardial infarction (AMI), unstable angina pectoris, coronary intervention procedure with percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) within 6 months.
  • cardiomyopathy of any etiology
  • presence of clinically significant valvular heart disease
  • history of atrial or ventricular arrhythmia requiring treatment; subjects with atrial fibrillation and optimally controlled ventricular rate (\< 100 beats per minute) are permitted.
  • subjects with atrial fibrillation and optimally controlled ventricular rate are permitted
  • transient ischaemic attack, or stroke within 6 months prior to screening
  • patients with symptomatic hypotension at screening
• Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of AZD5305

Other illness

• Any history of persisting (\> 2 weeks) severe pancytopenia due to any cause
• patient with known predisposition to bleeding (e.g., active peptic ulceration, recent \[within 6 months\] haemorrhagic stroke, proliferative diabetic retinopathy).
• Cardiac conditions as defined by the clinical study protocol
• Patients with myelodysplastic syndrome/acute myeloid leukaemia or with features suggestive of myelodysplastic syndrome (MDS)/acute myeloid leukaemia (AML).
• Known allergy or hypersensitivity to investigational product(s) or any of the excipients of the investigational product(s).
  • Prior malignancy whose natural history, in the Investigator's opinion, has the potential to interfere with safety and efficacy assessments of the investigational regimen.
  • other module-specific criteria may apply

Lab values

• Concomitant use of drugs that are known to prolong or shorten QT and have a known risk of Torsades de Pointes.

• Age ≥ 18 at the time of screening
• Histological or cytological confirmation of advanced malignancy considered to be suitable for study treatment and meeting module specific eligibility criteria..
• Eastern Cooperative Oncology Group Performance status (ECOG PS: 0-2)
• Life expectancy ≥ 12 weeks
• Progressive cancer at the time of study entry
• Patients must have evaluable disease as defined in module-specific criteria for Part A and Part B
• Adequate organ and marrow function as defined by the protocol.
• For Part B expansion cohorts: Provision of formalin-fixed and paraffin embedded (FFPE) tumour specimen is mandatory, where available, except if stated that it is optional in a specific Module.
  • For Part A:
  • \- Patients may have received up to one prior line of therapy with a PARPi-based regimen (either as a treatment or as maintenance)
  • For Part B:
  • \- Patients must not have received prior therapy with a PARPi-based regimen (either as a treatment or as maintenance).