A Modular Phase I/IIa, Open-label, Multicentre Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Preliminary Efficacy of Ascending Doses of AZD5305 as Monotherapy and in Combination With Anti-cancer Agents in Patients With Advanced Solid Malignancies

Trial ID: NCT04644068

Interventional - Phase 1/2 - Active, not recruiting

This research is designed to determine if experimental treatment with PARP inhibitor, AZD5305, alone, or in combination with anti-cancer agents is safe, tolerable, and has anti-cancer activity in patients with advanced solid tumors.

Conditions

• Ovarian Cancer
• Breast Cancer
• Pancreatic Cancer
• Prostate Cancer
• Additional Indications Below for Module 4 and 5
• Non-small Cell Lung Cancer
• Colorectal Cancer
• Bladder Cancer
• Gastric Cancer
• Biliary Cancer
• Cervical Cancer
• Endometrial Cancer
• Small Cell Lung Cancer Only in Module 5

Interventions

• AZD5305
• Paclitaxel
• Carboplatin
• T- Dxd
• Dato-DXd
• Camizestrant

Eligibility

Inclusion criteria

• 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).
• Key

Exclusion criteria

• 1. Nitrosourea or mitomycin C within 6 weeks of the first dose of study treatment
• 2. 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
• 3. Any other chemotherapy, immunotherapy or anticancer agents within 3 weeks of the first dose of study treatment
• 4. 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.
• Concomitant use of drugs that are known to prolong or shorten QT and have a known risk of Torsades de Pointes.
• 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.
• Any history of persisting (\> 2 weeks) severe pancytopenia due to any cause
• Treatment with any of the following:
• 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.
• 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
• Other cardiovascular diseases as defined by any of the following:
• 1. Symptomatic heart failure,
• 2. uncontrolled hypertension,
• 3. hypertensive heart disease with significant left ventricular hypertrophy
• 4. 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.
• 5. cardiomyopathy of any etiology
• 6. presence of clinically significant valvular heart disease
• 7. history of atrial or ventricular arrhythmia requiring treatment; subjects with atrial fibrillation and optimally controlled ventricular rate (\< 100 beats per minute) are permitted.
• 8. subjects with atrial fibrillation and optimally controlled ventricular rate are permitted
• 9. transient ischaemic attack, or stroke within 6 months prior to screening
• 10. patients with symptomatic hypotension at screening
• Patients with myelodysplastic syndrome/acute myeloid leukaemia or with features suggestive of myelodysplastic syndrome (MDS)/acute myeloid leukaemia (AML).
• 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
• 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

Sponsor

AstraZeneca

Source: ClinicalTrials.gov

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