A Study of DS-2248 in Participants With Advanced Solid Tumors

Inclusion Criteria: 1. A pathologically documented advanced solid malignant tumor refractory to standard treatment or for which no standard treatment is available. 2. Eastern Cooperative Oncology Group (ECOG) performance status ≤1. 3. Have adequate bone marrow function, defined as: * Platelet count ≥100x10\^9/L or more. * Hemoglobin (Hb) level ≥9.0 g/dL. * Absolute neutrophil count ≥1.5 x 10\^9/L. 4. Have adequate renal function, defined as: \- Creatinine clearance ≥60 mL/min, as calculated using the modified Cockcroft-Gault equation AND creatinine ≤1.5 times upper limit of normal(ULN). 5. Have adequate hepatic function, defined as: * Aspartate aminotransferase (AST) levels ≤3 times ULN (if liver metastases are present, ≤5x ULN) * Alanine aminotransferase (ALT) levels ≤3x ULN (if liver metastases are present, ≤5x ULN * Bilirubin ≤1.5x ULN 6. Have adequate blood clotting function, defined as: \- Prothrombin time and activated partial thromboplastin time ≤1.5x ULN 7. Participants should be able to provide written informed consent, comply with protocol visits and procedures, be able to take oral medication, and not have any active infection or chronic co-morbidity that would interfere with therapy. 8. Participants (male and female) of childbearing/reproductive potential must agree to use double-barrier contraceptive measures or avoid intercourse during the study and for 90 days after the last dose of study drug. If female and of childbearing potential, must have a negative result of a pregnancy test (serum or urine)within 72 hours prior to initiating study treatment. Surgically sterile individuals and postmenopausal females are considered not having child-bearing potential. 9. Participants must be fully informed about their illness and the investigational nature of the study protocol (including foreseeable risks and possible side effects) and must sign and date an Institutional Review Board approved informed consent form (including Health Insurance Portability and Accountability Act authorization, if applicable) before performance of any study-specific procedures or tests. 10. Participants must be willing to provide pre-existing diagnostic or resected tumor samples, such as formalin-fixed paraffin-embedded sections, if available. Providing fresh pre-treatment tumor biopsy is optional for participants in dose escalation cohorts and in dose expansion Stage 1. Post-treatment biopsies are optional for all the participants in the study (dose escalation and dose expansion cohorts). Additional Inclusion Criteria for Part 2 (Dose Expansion) 1. Pathologically documented stage IIIB/IV non-small cell lung cancer. 2. Measurable disease based on Response Evaluation Criteria In Solid Tumors (RECIST) criteria, Version 1.1. 3. Participants must meet 1 of the following 3 criteria in order to be included in Part 2: 1. Acquired resistance to reversible Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitor (EGFR-TKI), which should meet the following criteria: * Previous treatment with single-agent therapy (erlotinib, gefitinib, afatinib or others). * Either of the following: A tumor that harbors an EGFR mutation known to be associated with drug sensitivity (i.e., G719X, exon 19 deletion, L858R, L861Q) -OR- Prior objective clinical benefit from EGFR-TKI, as evidenced by complete response (CR), partial response (PR), or stable disease (SD) ≥6 months as defined by RECIST or World Health Organization criteria. * Systemic progression of disease as defined by RECIST or World Health Organization criteria while treatment with gefitinib, erlotinib, afatinib or others. * No intervening therapy other than EGFR-TKIs (erlotinib, gefitinib, afatinib or others) after progression on an EGFR-TKI. * Pre-treatment biopsy (performed via bronchoscopy or imaging guidance) for molecular testing of the tumor is desired but not mandatory for enrollment in Stage 1. However, pre-treatment biopsy within 21 days prior to the first day of treatment is required for enrollment in Stage 2. 2. Presence of ALK fusion gene in the tumor demonstrated by fluorescence in situ hybridization (FISH) and the participant has acquired resistance to ALK inhibitor therapy. Exclusion Criteria: 1. History of second malignancies or primary central nervous system malignancies, except adequately treated non-melanoma skin cancer, curatively treated in-situ disease, or other solid tumors curatively treated, with no evidence of disease for ≥3 years. 2. Gastrointestinal diseases that could affect the absorption of DS-2248. 3. Subjects with peptic ulcer disease requiring on-going treatment with pH-modifiers 4. Subjects with history of inflammatory bowel disease. 5. Subjects with retinal or uveal diseases including macular degeneration with central vision loss, retinal detachment, diabetic retinopathy, and uveitis. 6. Recipient of a stem cell or bone marrow transplant. 7. Has a concomitant medical condition that would increase the risk of toxicity, in the opinion of the Investigator or Sponsor. 8. 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). 9. Has unresolved toxicities from previous anti-cancer therapy, defined as toxicities (other than alopecia) not yet resolved to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (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 (e.g., Grade 2 chemotherapy-induced neuropathy). 10. Systemic treatment with anticancer therapy, antibody-based therapy, retinoid therapy, or hormonal therapy (except megestrol acetate as supportive care) 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 Tyrosine Kinase Inhibitors within 7 days for erlotinib and afatinib and 10 days for gefitinib before study drug treatment. 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. 11. Therapeutic radiation therapy or major surgery within 4 weeks before study drug treatment or palliative radiation therapy within 2 weeks before study drug treatment. 12. Participation in a clinical drug study within 3 weeks for small-molecule TKIs before study drug treatment, or current participation in other investigational procedures. 13. Concomitant treatment with potent inducers or potent inhibitors of cytochrome P450 3A4 (CYP3A4). 14. Concomitant treatment with a medication known to cause renal tubular damage or reduce renal perfusion at the dose administered, including aminoglycosides, amphotericin B, pentamidine, nonsteroidal anti-inflammatory drugs, and zoledronate. 15. Corrected QT interval (QTc by Bazett's formula) prolongation at rest, where the mean QTc interval is \>450 msec based on triplicate ECG. 16. Pregnant or breastfeeding. 17. 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. 18. Less than 1 week since using systemically acting drugs that increase gastric pH, such as H2-blockers and proton pump inhibitors. Antacids should be avoided within 48 hours of the first dose of DS-2248. 19. Use of St. John's Wort (hypericin) is not permitted for 30 days before and during the study. Foods or beverages containing grapefruit should be avoided within 48 hours before and during the study. Additional Exclusion Criteria for Part 2 (Dose Expansion) 1. Prior treatment with Hsp90 inhibitors 2. Intervening therapy after progression on an EGFR-TKI (erlotinib, gefitinib, afatinib or others), unless re-treated with EGFR-TKI.