MONETTE: This phase II study is evaluating how safe, tolerable and effective targeted therapy (ceralasertib) is alone, and in combination with immunotherapy (durvalumab), in people with inoperable or advanced melanoma and primary or secondary resistance to PD(L)1 InhibitionA Randomised, Open-Label, Phase 2 Study of Ceralasertib Monotherapy and Ceralasertib Plus Durvalumab in Patients With Unresectable or Advanced Melanoma and Primary or Secondary Resistance to PD-(L)1 Inhibition

Exclusion

• Patients must not have experienced a toxicity that led to permanent discontinuation of prior checkpoint inhibitors (CPI) treatment.
• History of another primary malignancy except for malignancy treated with curative intent with no known active disease ≥ 3 years before the first dose of study treatment
• Uveal melanoma
• Must not have experienced a Grade ≥ 3 immune-related AE or an immune-related neurologic or ocular AE of any grade while receiving prior immunotherapy
• History of symptomatic congestive heart failure, unstable angina pectoris, uncontrolled cardiac arrhythmia, which is symptomatic or requires treatment (CTCAE Grade 3), symptomatic or uncontrolled atrial fibrillation despite treatment, or asymptomatic sustained ventricular tachycardia. Patients with atrial fibrillation controlled by medication or arrhythmias controlled by pacemakers may be permitted upon discussion with the study clinical lead.
• History of organ transplant that requires use of immunosuppressive medications
• Inadequate bone marrow and impaired hepatic or renal function
• Known active infection requiring systemic therapy, active hepatitis infection, positive hepatitis C virus antibody, hepatitis B virus (HBV) surface antigen or HBV core antibody (anti-HBc), at screening
• Patients with confirmed COVID-19 infection by polymearse chain reaction test who have not made a full recovery.