Patient must meet eligibility to come onto the Intercept Master Protocol (as detailed in linked entry ACTRN12621000439842).
In order to be eligible to the MBG453 treatment arms exclusion criteria includes:
- Prior allogeneic stem cell transplantation within 3 months of post-conditioning or on greater than or equal to 10mg/day prednisolone for graft vs host disease
- QT-interval corrected according to Fridericia’s formula (QTcF) greater than 470ms (except for right bundle branch block)
- Subject is HIV positive
- Patients with greater than or equal to 5% myeloblasts in bone marrow on morphologic assessment
- Evidence of other clinically significant uncontrolled condition(s) including, but not limited to:
a. Uncontrolled and/or active systemic infection (viral, bacterial or fungal)
b. Acute/Chronic hepatitis B virus (HBV) or hepatitis C (HCV) requiring treatment.
- Systemic chronic corticosteroid therapy (greater than or equal to 10 mg/day prednisone or equivalent) or any immunosuppressive therapy within 7 days of first dose of study treatment. Topical, inhaled, nasal and ophthalmic steroids are allowed.
- For initial enrolment to INTERCEPT therapy, patients who have received previous TIM3 inhibitor treatment are excluded. This exclusion criteria does not apply to patients crossing-over from MBG453 arm to the combination MBG453 + azacitidine arm, unless MBG453 was ceased due to MBG453-related toxicity.
- Patients with active, known or suspected autoimmune disease. Patients with vitiligo, type I diabetes, residual hypothyroidism only requiring hormone replacement, psoriasis not requiring systemic treatment or conditions not expected to recur should not be excluded
- History of or current drug-induced interstitial lung disease or pneumonitis grade greater than or equal to 2
- Subject has been diagnosed with another malignancy, unless disease-free for at least 2 years and not needing active treatment. Patients with fully excised BCC/SCC/CIN or other minor malignancy are not excluded
- Subject has clinically significant abnormality of coagulation profile, such as disseminated intravascular coagulation
- Use of any live vaccines against infectious diseases (i.e. Influenza, varicella, pneumococcus) within 4 weeks of initiation of study treatment
- Impaired cardiac function or clinically significant cardiac disease, including any of the following:
• Clinically significant and/or uncontrolled heart disease such as congestive heart failure requiring treatment (NYHA Grade greater than or equal to 2) with an LVEF of less than 40%, uncontrolled hypertension or clinically significant arrhythmia
• Acute myocardial infarction or unstable angina pectoris less than 3 months prior to study entry
- Known hypersensitivity to azacitidine or mannitol.