This is a single center, phase I/Ib clinical trial evaluating the combination of the poly adenosine diphosphate-ribose polymerase (PARP) inhibitor olaparib with the DNA methyltransferase (DNMT) inhibitor ASTX727, which is an oral formulation of decitabine with cedazuridine (a cytidine deaminase inhibitor that allows for oral administration). The study population consists of adults with advanced/metastatic solid tumor malignancies with germline or somatic mutations in the HRR pathway (i.e., BReast CAncer gene 1 (BRCA1), BReast CAncer gene 2(BRCA2), Partner And Localizer of BRCA2 (PALB2), ATM, and/or Checkpoint kinase 2 (CHEK2) mutations).
Expansion Cohort A (n=6): Germline mutation* (with or without accompanying somatic mutation) in one or more of the following genes: BRCA1, BRCA2, PALB2, ATM, and/or CHEK2;
Expansion Cohort B (n=6): Germline and/or somatic mutation* in one or more of the following genes: BRCA1, BRCA2, PALB2, ATM, and/or CHEK2.
Testing for DNA repair mutations should occur prior to study consent or enrollment via a CLIA-approved test.
Has measurable disease per RECIST 1.1 as assessed by the investigator. Lesions situated in previously irradiated areas are considered measurable if progression has been demonstrated in such lesions.
Has received systemic anticancer therapies within 3 weeks of first dose, radiation within 2 weeks, antibody therapy within 4 weeks. Concomitant administration of Luteinizing hormone-releasing hormone (LHRH) analogues for prostate cancer and somatostatin analogues for neuroendocrine tumors are allowed as per standard of care.
Has not recovered from adverse events due to prior anti-cancer therapy to <= grade 1 (CTCAE v5.0) or baseline (other than alopecia).
Receipt of any other investigational agents or devices within 3 weeks prior to initiation of trial therapy.
Unable to swallow oral medications
Varun Monga, MBBS
Lead sponsor
University of California, San Francisco
Sponsor institution
National Cancer Institute (NCI)
Collaborator