A Phase 2 Study of AZD1775 in SETD2-Deficient Advanced Solid Tumor Malignancies (ETCTN10170)
Ana De jesus-acosta
Johns Hopkins Kimmel Cancer Center in Baltimore
PRIMARY OBJECTIVES:I. To determine the objective response rate by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria of adavosertib (AZD1775) in advanced solid tumor malignancies other than clear cell renal cell carcinoma with evidence of biallelic loss of SETD2 using next-generation sequencing panel.II. To determine the objective response rate by RECIST 1.1 criteria of AZD1775 in clear cell renal cell carcinoma with evidence of loss of SETD2 using next-generation sequencing panel.SECONDARY OBJECTIVES:I. To determine the clinical benefit rate and duration of response of AZD1775 in SETD2-deficient tumors other than clear cell renal cell carcinoma.II. To determine the clinical benefit rate and duration of response of AZD1775 in SETD2-deficient clear cell renal cell carcinoma subgroup.III. To characterize the safety profile of AZD1775. IV. To determine whether H3K36me3 expression by immunohistochemical assay is associated with clinical outcomes.
•Cohort A: Histologically confirmed locally advanced or metastatic solid tumor malignancy other than clear cell renal cell carcinoma with progression on at least one prior systemic therapy and presence of biallelic loss of SETD2 detected in tumor tissue.•Cohort B: Patients with histologically confirmed locally advanced or metastatic clear cell renal cell caricnoma (with clear cell component on pathology), who have been treated with at least one prior systemic therapy for locally advanced or metastatic disease, including either tyrosine kinase inhibitor and/or immune checkpoint inhibitor, with evidence of SETD2 mutation on CLIA-certified next generation sequencing panelECOG equal to less than 1 (Karnofsky greater than equal to 70%)
Patients receive adavosertib orally (PO) once daily (QD) on days 1-5 and 8-12. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.After completion of study treatment, patients are followed up for 30 days.
03/05/2019 05:03 AM