A multi-center, open-label, first-in-human, phase I dose-escalation study of single agent RO5503781, a small molecule MDM2 inhibitor, administered orally in patients with advanced malignancies, except leukemia.

1. Patient must have histologically or cytologically confirmed advanced malignancies, except all forms of leukemia, for which standard curative or palliative measures do not exist, are no longer effective, or are not acceptable to the patient.;2. Measureable disease (by RECIST criteria version 1.1 for solid tumors or by Cheson Criteria for malignant lymphomas or evaluable disease prior to the administration of study drug.;3. Patients must be willing to provide archival tumor tissue for biomarker testing (if available). ;4. Ability to understand and the willingness to sign a written informed consent form and comply with all study requirements.;5. Life expectancy of >=12 weeks.;6. Minimum weight of 35 kg.;7. Age >= 18 years.;8. ECOG performance status of 0 to 1.;9. Female patients with child-bearing potential and post menopausal females with less than two years of amenorrhea must have a negative serum pregnancy test within 72 hours of the study first drug administration. ;10. Patient must be willing to use effective methods of contraception. Female patients must be postmenopausal (defined as two years of amenorrhea), surgically sterile, or they must agree to use a physical barrier method of contraception. Oral or injectable contraceptive agents cannot be the sole method of contraception. Male patients must be surgically sterile or agree to use acceptable method of contraception.;Country Specific Requirement for France: All patients must be willing to use effective methods of contraception while receiving study treatment and for 10 days after the last dose of RO5503781. Female patients must be postmenopausal (>=2 years of amenorrhea), surgically sterile, or they must agree to use a physical barrier method of contraception. Oral or injectable contraceptive agents can not be the sole method of contraception. Male patients must be surgically sterile or agree to use acceptable method of contraception.;11. There are no limitations on additional, allowable type and amount of prior anti-tumor therapy. Acute toxicities from any prior anti-tumor therapy, surgery, or radiotherapy must have resolved to NCI-CTCAE Grade <= 1. Care should be taken for patients who have developed cytopenias with prior radiotherapy to assure adequate bone marrow recovery prior to study initiation. The last dose of prior therapy must be >= 21 days prior the first administration of study drug RO5503781 (or >=5 x terminal half-life of the therapy for any therapy given less than 21 days previously). ;12. Adequate bone marrow function as defined by:;• ANC of >= 1.5 x 109/L. ;• Platelets count >= lower limit of normal ;• Hemoglobin of >= 9.0 g/dl. ;13. Adequate hepatic function assessed by: ;• Serum total bilirubin <= 2 mg/dl, unless resulting from hemolysis or known Gilbert*s disease.;• AST/ALT <= 2.5 x institutional ULN (or <= 5 x ULN if liver metastases). ;14. Adequate renal function assessed by Serum creatinine within reference lab normal limits OR creatinine clearance >= 50 calculated by Cockcroft Gault (if in the PI judgment, serum creatinine level may not adequately reflect renal function). ;15. Patients with stable CNS metastases (have had therapy or don*t require therapy, are off steroids, have no change on screening CT or MRI and are asymptomatic), are eligible. ;16. Patients with chronic, stable and rate-controlled Atrial Fibrillation are eligible.;17. Biomarker Cohorts and Apoptosis Imaging;Cohort ONLY: Patients in consideration for the;biomarker cohort or apoptosis imaging cohort;(Netherlands Only) must consent and be able to;undergo paired biopsies for tumor biomarker;analyses.;18. Biomarker Cohorts and Apoptosis Imaging;Cohort ONLY: patient*s tumor size must be >= 2;cm and must consent to undergo [18F]-FLT-PET;imaging (biomarker cohort only), or [18F]-FLTPET;imaging and [18F]CP18 imaging (apoptosis;imaging cohort).;19. Apoptosis Imaging Cohort (Netherlands Only):;Patients must consent to provide all CT scans;up to 6 months prior to entering the study, if;available.

1. Patients with history of any form of leukemia except for Stage 0 and 1 chronic lymphocytic leukemia (CLL) not requiring treatment in addition to their underlying solid tumor.;2. Patients who have received hormonal therapy within the 2 weeks prior to the first dose of study medication. Patients with prostate cancer who are not surgically castrated should remain on GnRH analogues. ;3. Patients who are using other investigational agents or who had received investigational drugs <= 4 weeks prior to study treatment start.;4. Patients with pre-existing GI disorders that may interfere with proper absorption of the drug(s), as per investigator discretion.;5. Patients with history of allergic reactions attributed to components of the formulated product.;6. Patients with history of seizure disorders or unstable CNS metastases. ;7. Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as:;• unstable angina, symptomatic or otherwise uncontrolled arrhythmia requiring medication (does not include stable, lone atrial fibrillation), QTcF > 480 msecs based on the average of 3 screening ECG*s , uncontrolled hypertension., symptomatic congestive heart failure (NYHA II, III, IV), myocardial infarction <= 6 months prior to first study treatment, serious uncontrolled cardiac arrhythmia, cerebrovascular accidents <= 6 months before study treatment start.;• any active (acute or chronic) or uncontrolled infection/disorders that impair the ability to evaluate the patient or for the patient to complete the study. ;• nonmalignant medical illnesses that are uncontrolled or whose control may be jeopardized by this study treatment, such as, severe diabetes mellitus that is not controlled with medical management.;8. Patients who must receive CYP2C8 inhibitors, substrates or inducers, strong CYP 3A4 inducers or moderate/strong CYP3A4 inhibitors listed in protocol while on study. Substrates and Inhibitors listed in protocol must be discontinued 7 days prior to start of study medication. Inducers found in protocol must be discontinued 14 days prior to start of study medication.;9. Patients with evidence of electrolyte imbalance such as hypokalemia, hyperkalemia, hypocalcemia, hypercalcemia, hypomagnesemia, and hypermagnesemia of Grade >= 2, as per NCI-CTCAE, version 4.03. Treatment for correction of above electrolyte imbalances is permitted during screening to meet eligibility. ;10. Pregnant or breast feeding patients.;11. Patients with reproductive potential not willing to use effective method of contraception.;Country Specific Requirement for France: Patients with reproductive potential not willing to use effective methods of contraception while receiving study treatment and for 10 days after the last dose of RO5503781.;12. HIV-positive patients who are currently receiving combination anti-retroviral therapy.;13. Patients with known coagulopathy, platelet disorder or history of non-drug induced thrombocytopenia.;14. Patients receiving oral or parenteral anticoagulants/antiplatelet agents (e.g. chronic daily treatment with aspirin (> 325 mg/day), clopidogrel or subcutaneous anticoagulant prophylaxis). Patients may receive anticoagulant flushes for maintenance of indwelling catheters.;15. Patients who refuse to potentially receive blood products and/or have a hypersensitivity to blood products.;16. Patients with known bone marrow disorders which may interfere with bone marrow recovery, (i.e. tumor involvement, fibrosis), or patients with delayed recovery from prior chemoradiotherapy (i.e. after radiation to the pelvis).;17. A physical exam or laboratory finding that contra-indicates the use of investigational therapy or otherwise places the patient at excessively high risk for treatment, as determined by the study investigator. A discussion between the Investigator and Sponsor regarding eligibility is encouraged for such cases.;18. Biomarker Cohorts and Apoptosis Imaging;Cohorts ONLY: patients who have had a;hypersensitivity reaction to FLT or 18F will be;excluded from having an [18F]-FLT-PET scan.;19. Apoptosis Imaging Cohort ONLY (Netherlands;Only): patients who have had a hypersensitivity;reaction to [18F]CP18 or CP18 will be excluded;from this cohort.