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Cabozantinib inhibits multiple receptor tyrosine kinases, including the TAM kinase family, and may enhance response to immune checkpoint inhibitors. One cohort of the ongoing phase Ib COSMIC-021 study (NCT03170960) evaluating cabozantinib plus the PD-L1 inhibitor atezolizumab in men with metastatic castration-resistant prostate cancer (mCRPC) that has progressed in soft tissue on/after enzalutamide and/or abiraterone treatment for metastatic disease has shown promising efficacy. Here, we describe the rationale and design of a phase III trial of cabozantinib plus atezolizumab versus a second novel hormone therapy (NHT) in patients who have previously received an NHT for mCRPC, metastatic castration-sensitive PC or nonmetastatic CRPC and have measurable visceral disease and/or extrapelvic adenopathy - a population with a significant unmet need for treatment options. Trial Registration Clinical Trial Registration: NCT04446117 (ClinicalTrials.gov) Registered on 24 June 2020. [ABSTRACT FROM AUTHOR]

Patients with refractory or relapsed acute myeloid leukemia (R/R AML) have a poor prognosis, with a high unmet medical need. Idasanutlin is a small-molecule inhibitor of MDM2, a negative regulator of tumor suppressor p53. By preventing the p53-MDM2 interaction, idasanutlin allows for p53 activation, particularly in patients with TP53 wild-type (WT) status. MIRROS (NCT02545283) is a randomized Phase III trial evaluating idasanutlin + cytarabine versus placebo + cytarabine in R/R AML. The primary end point is overall survival in the TP53-WT population. Secondary end points include complete remission rate (cycle 1), overall remission rate (cycle 1) and event-free survival in the TP53-WT population. MIRROS has an innovative design that integrates a stringent interim analysis for futility; continuation criteria were met in mid-2017 and accrual is ongoing. Trial registration number: NCT02545283. [ABSTRACT FROM AUTHOR]

Treatment for relapsed/refractory multiple myeloma (RRMM) remains an unmet need. Isatuximab, an anti-CD38 monoclonal antibody has shown efficacy and tolerability as a monotherapy and combination therapy in Phase I/II studies in RRMM. Here, we describe the design of the Phase III ICARIA-MM study (NCT02990338) which will evaluate isatuximab in combination with pomalidomide (Pom) and low-dose dexamethasone (dex) (Pom/dex) versus Pom/dex alone in RRMM. Patients will be randomized in a 1:1 ratio. The primary endpoint is progression-free survival. Response will be determined by an independent response review committee using IMWG criteria (2016) and safety will be assessed throughout. Approximately 300 patients (150 in each arm) are expected to enroll. The first patient was recruited in January 2017 and accrual is ongoing. [ABSTRACT FROM AUTHOR]