AZD4573 as Monotherapy or in Combinations with Anti-cancer Agents in Patients with r/r PTCL or r/r cHL

Exclusion Criteria

• Type of Participant and Disease Characteristics:
• - PTCL only: Presence of bulky disease (defined as largest lymphoma lesion ≥ 10 cm) or a LDH value > 3 x ULN.
• - PTCL only: Diagnosis of any of the following: Lymphoblastic/precursor T-cell lymphoma or leukaemia; T-cell prolymphocytic leukaemia; T-cell large granular lymphocytic leukaemia; Cutaneous T-cell lymphoma (eg, primary cutaneous type ALCL, mycosis fungoide/Sezary syndrome).
• Medical Conditions:
• - With the exception of alopecia and neuropathy, presence of any unresolved non haematological toxicities from prior therapy greater than CTCAE Grade 1 at the time of starting study treatment.
• - Presence of, or history of, CNS lymphoma, leptomeningeal disease, or spinal cord compression.
• - History of prior non-haematological malignancy except for the following:
• • Malignancy treated with curative intent and with no evidence of active disease present for more than 1 year prior to screening and felt to be at low risk for recurrence by treating physician.
• • Adequately treated lentigo maligna melanoma without current evidence of disease or adequately controlled non-melanomatous skin cancer.
• • Adequately treated carcinoma in situ without current evidence of disease.
• - Any evidence of:
• • Severe or uncontrolled systemic disease (eg, severe hepatic impairment, interstitial lung disease [bilateral, diffuse, parenchymal lung disease]).
• • Current unstable or uncompensated respiratory or cardiac conditions.
• • Uncontrolled hypertension.
• • Uncontrolled active systemic fungal, bacterial, viral, or other infection (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment).
• • IV anti-infective treatment within 1 week before first dose of study drug.
• - Known history of infection with HIV.
• - Serologic status reflecting active hepatitis B or C infection:
• • Participants who are hepatitis B core antibody (anti-HBc) positive and who are surface antigen negative will need to have a negative PCR result before enrolment. Those who are hepatitis B surface antigen positive or hepatitis B PCR-positive will be excluded.
• • Participants who are hepatitis C antibody positive will need to have a negative PCR result before enrolment. Those who are hepatitis C PCR-positive will be excluded.
• - Any of the following cardiac criteria:
• • Resting QT interval corrected using Fridericia’s formula (QTcF) ≥ 470 msec obtained from a single ECG.
• • Any clinically important abnormalities in rhythm (except for participants with a pacemaker in place), conduction or morphology of resting ECG (e.g., complete left bundle branch block, third degree heart block).
• • Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age.
• - Documented confirmation and ongoing treatment of adrenal gland insufficiency or pancreatitis.
• - Undergone any of the following procedures or experienced any of the following conditions within 6 months prior to first dose:
• • Coronary artery bypass graft
• • Angioplasty
• • Vascular stent
• • Myocardial infarction
• • Angina pectoris
• • CHF (New York Heart Association Class ≥ 2)
• • Ventricular arrhythmias requiring continuous therapy
• • Atrial fibrillation, which is judged as uncontrolled by the treating physician
• • Haemorrhagic or thrombotic stroke, including transient ischemic attacks or any other CNS bleeding