Safety and Tolerability of DS-7423 in Subjects With Advanced Solid Malignant Tumors

Exclusion Criteria

• •History of second malignancy and primary central nervous system malignancies, except adequately treated nonmelanoma skin cancer, curatively treated in situ disease, or other solid tumors curatively treated, with no evidence of disease for \>= 3 years
• •Gastrointestinal diseases that could affect the absorption of DS-7423
• •Subjects with a fasting glucose \> 126 mg/dL (\> 7 mmol/L)
• •History of diabetes mellitus (Type I or II) or hemoglobin A1c (HbA1c) \> 7.0%
• •Tested positive for hepatitis B or C serological markers (HBsAg or antiHCV)
• •Recipient of live vaccine within 1 month of or during study drug treatment
• •Concomitant use of chronic systemic corticosteroids
• •Subjects requiring daily supplemental oxygen
• •Recipient of a stem cell or bone marrow transplant
• •Has a concomitant medical condition that would increase the risk of toxicity, in the opinion of the investigator or sponsor
• •Clinically active brain metastases, defined as untreated and symptomatic, or requiring therapy with steroids or anticonvulsants to control associated symptoms. Subjects with treated brain metastases that are no longer symptomatic and who require no treatment with steroids may be included in the study if they have recovered from the acute toxic effect of radiotherapy. A minimum of 4 weeks must have elapsed between the end of whole brain radiotherapy and study enrollment (2 weeks for stereotactic radiotherapy)
• •Has unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to NCI CTCAE, Version 4.0, grade =\< 1 or baseline. Subjects with chronic grade 2 toxicities may be eligible per the discretion of the investigator or sponsor (eg, grade 2 chemotherapy-induced neuropathy)
• •Systemic treatment with anticancer therapy, antibody-based therapy, retinoid therapy, or hormonal therapy within 3 weeks before study drug treatment; or treatment with nitrosoureas or mitomycin C within 6 weeks before study drug treatment; or treatment with small-molecule targeted agents within 2 weeks, or 5 half-lives before study drug treatment, whichever is longer. Previous and concurrent use of hormone replacement therapy, the use of gonadotropin-releasing hormone modulators for prostate cancer, and the use of somatostatin analogs for neuroendocrine tumors are permitted if such therapy has not been changed within 60 days before study drug treatment
• •Therapeutic radiation therapy or major surgery within 4 weeks before study drug treatment or palliative radiation therapy within 2 weeks before study drug treatment
• •Participation in a clinical study within 3 weeks (2 weeks or 5 half-lives, whichever is longer, for small-molecule targeted agents) before study drug treatment, or current participation in other investigational procedures
• •Concomitant treatment with strong inducers or strong inhibitors of cytochrome P450 (CYP) 3A4/5, and CYP2C8
• •Prolongation of corrected QT interval by Fridericia's method (QTcF) at rest, where the mean QTcF interval is \> 450 millisecond (ms) for males and \> 470 ms for females based on triplicate ECG
• •Pregnant or breastfeeding
• •Substance abuse or medical, psychological, or social conditions that may, in the opinion of the investigator, interfere with the subject's participation in the clinical study or evaluation of the clinical study results
• •Prior NCI CTCAE, Version 4.0, grade 3/4 toxicity from a dual phosphatidylinositol 3 kinase (PI3K)/mammalian target of rapamycin (mTOR) inhibitor (including, but not limited to, BEZ-235, XL765, GDC-0980, SF1126, GSK2126458, PF4691502, and PF05212384), requiring dose reduction and/or study discontinuation
• •\- Prior treatment with a dual PI3K/ mTOR inhibitor (including, but not limited to, BEZ-235, XL765, GDC-0980, SF1126, GSK2126458, PF4691502, and PF05212384)