Alternative Dosing for CRLX101(NLG207) Alone, With Avastin and With mFOLFOX6 in Advanced Solid Tumors

Inclusion Criteria: (All Subjects) * Male or female adult subjects ≥18 years of age * Diagnosis of histologically or cytologically confirmed for: * For Schedule 1 and 2: advanced solid tumor malignancy that is refractory to standard therapy and/or for whom no further standard therapy is available * For Schedule 3: advanced/metastatic tumors for which mFOLFOX6 is appropriate, or advanced/metastatic tumors that may be sensitive to each component of mFOLFOX6 or sensitive to topoisomerase 1 inhibitors including pancreatic, colorectal, esophageal, gastric, bladder or ovarian cancer, triple-negative breast cancer, small cell lung cancer (SCLC), cholangiocarcinoma, among others * For Schedules 1 and 2: Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 2, For Schedule 3: ECOG Performance Status of 0 or 1 * Life expectancy \>12 weeks in the opinion of the Investigator * Subjects with acceptable pre-study\* hematology and biochemistry labs ≤3 days prior to Week 1 Day 1 (W1D1) defined as: * absolute neutrophil count (ANC) ≥1.500 cells / µL (1.5 x 10°/L, without growth factor support * platelet count ≥100,000 cells/µL (100 x 10° cells/L), without growth factor support * hemoglobin ≥9 g/dL (90/g/L) * serum total bilirubin ≤1.5 upper limit of normal (ULN), unless Gilbert's disease * alanine transaminase (ALT) or aspartate transaminase (AST) ≤2.5 x ULN, (5 x ULN for subjects with liver metastases) * calculated or measured creatinine clearance ≥40 mL/min * NOTE: If screening hematology and biochemistry labs are performed ≤3 days prior to W1D1, additional pre-study labs do not need to be repeated to confirm eligibility. However, if screening hematology and biochemistry labs are performed greater than 3 days prior to W1D1, additional pre-study labs will need to be performed to confirm continued eligibility to ensure labs remain acceptable per protocol * Females of childbearing potential must agree to use two effective methods of contraception (or abstain completely from heterosexual intercourse) from the time of informed consent and for 30 days following last dose of study drug * NOTE: Females of childbearing potential are defined as women physically capable of becoming pregnant unless the female subject cannot have children due to surgery or other medical reasons (effective tubal ligation, ovaries or the uterus removed, or are post-menopausal). Fertile males of childbearing potential are defined as men who are sexually capable to impregnate the female partner even if surgically sterilized (i.e., vasectomy). * highly effective methods of contraception include intra-uterine device (IUD) and hormonal contraception (oral, injectable, patches or implant) * effective methods of contraception include barrier methods (latex condom, diaphragm with spermicide, cervical cap, sponge) * when possible, subjects should be strongly encouraged to include at least one highly effective method of contraception * Male subjects must agree to use appropriate method of barrier contraception (latex condom with a spermicidal agent) or abstain completely from heterosexual intercourse fro the time of informed consent and for 120 days following last dose of study drug unless female partner absolutely cannot have children because of surgery or for other medical reasons * Negative urine pregnancy test * Ability to understand and willingness to sign a written informed consent form * Able to comply with study visit schedule and assessments Exclusion Criteria: (All Subjects) * Subject has received: * chemotherapy or small molecular targeted therapy \<2 weeks prior to W1D1 * approved antibody therapy \<5 half-lives from W1D1 (or 4 weeks since last therapy, whichever is the shortest) * local palliative radiation \<14 days from W1D1 * invasive surgery requiring general anesthesia \<30 days from W1D1 * chemotherapy with nitrosoureas or mitomycin C \<45 days from W1D1 * Uncontrolled grade 2 or greater toxicity except alopecia related to any prior treatment (i.e., chemotherapy, targeted therapy, radiation or surgery) within 7 days prior to W1D1 unless approved by the Medical Monitor * Prolongation of QT/QTc interval (QTc interval \>470) using the Fredericia method of QTc analysis * Women who are pregnant or nursing * Any known human immunodeficiency virus (HIV) infection or acquired immune deficiency syndrome (AIDS) or any concurrent infection requiring IV antibiotics * Any known clinically significant or concurrent acute liver disease, including viral hepatitis * Primary brain malignant tumors * Subjects with uncontrolled symptomatic central nervous system (CNS) involvement * Subjects requiring steroids at stable dose (\>4 mg/day dexamethasone or equivalent) for at least 2 weeks * Uncontrolled hypertension \>150/100 mmHg * Concurrent participation in any other investigational therapeutic study, unless non-interventional study and approved by Sponsor * History of stroke, deep venous thrombosis (DVT), transient ischemic attack (TIA), unstable angina, or myocardial infarction within 3 months prior to W1D1 * Uncontrolled concurrent disease or illness including but not limited to: * symptomatic congestive heart failure (NYHA Class III or IV) per the NYHA Classification, unstable angina pectoris, clinically significant cardiac arrhythmia * unstable or untreated cardiac conditions or ejection fraction of \<50% as determined by echocardiogram (ECHO) or multiple gated acquisition scan (MUGA) * diabetes mellitus (i.e., fasting blood glucose \>220 despite acceptable chronic diabetes therapy) * psychiatric illness that would limit compliance with study requirements, as determined by the Investigator * Other severe, acute, or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration or that may interfere with the interpretation of study results and, in the judgment of the Investigator, would make the subject inappropriate for the study. * Known hypersensitivity to any component of CRLX101 or excipient or documented medical condition that would prohibit adequate pre-medication with antihistamine. * Presence of ≥Grade 1 cystitis Exclusion Criteria for Subjects Enrolled in Schedule 2 Only * Minor surgical procedure, excluding placement of a vascular access device, within 24 hours prior to W1D1. * Cardiovascular disease defined as congestive heart failure (NYHA Class II, III, or IV) per the NYHA Classification, angina pectoris requiring nitrate therapy, or myocardial infarction within the last 6 months prior to therapy * Uncontrolled hypertension (defined as the presence of systolic blood pressure ≥150 mmHg or diastolic blood pressure ≥100 mmHg on two separate occasions. Blood pressure must be controlled to a systolic blood pressure \<150 mmHg and/or to diastolic blood pressure \<100 mmHg prior to study treatment), or any prior history of hypertensive crisis or hypertensive encephalopathy * Peripheral vascular disease \>Grade 1 * Known congenital long QT syndrome, history of torsades de pointes or ventricular tachycardia. * Known history of pulmonary hypertension or non-infectious interstitial pneumonitis. * History or evidence of thrombotic or hemorrhagic disorders: including cerebrovascular accident (CVA) / stroke or transient ischemic attack (TIA), intracerebral hemorrhage or sub- arachnoid hemorrhage ≤ 6 months prior to W1D1 * Chronic daily aspirin \>325 mg/day or clopidogrel (\>75 mg/day) * History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to randomization * Any of the following serious, non-healing conditions:wound, ulcer, or bone fracture * Proteinuria at screening as demonstrated by either: urine dipstick ≥2+ (subjects discovered to have a ≥2+ proteinuria on dipstick urinalysis at baseline should undergo 24-hour urine collection and must demonstrate \<1g of protein in 24 hours to be eligible): 24-hour urine collection demonstrates \>1g of protein in 24 hours * Immunocompromised subjects, including known seropositivity for human immunodeficiency virus (HIV), or current or chronic hepatitis B and/or hepatitis C infection (as detected by positive testing for hepatitis B surface antigen \[HbsAg\] or antibody to hepatitis C virus \[anti HCV\] with confirmatory testing). \[Note: testing is not mandatory to be eligible for the study. However, if a subject is at risk for having undiagnosed hepatitis C virus (HCV) (due to history of injection drug use or due to geographic location for example), testing at screening should be considered\] * Chronic treatment with corticosteroids (prednisone \>12.5 mg/day or dexamethasone \>2 mg/day excluding inhaled steroids Exclusion Criteria for Subjects Enrolled in Schedule 3 Only * Known hypersensitivity to 5FU, oxaliplatin or other platinum agent, or to their excipients * Known dihydropyridine dehydrogenase (DPD) enzyme deficiency (testing not required) * Baseline peripheral neuropathy grade ≥ 2 * Progressive disease within ≤ 6 months of completing an oxaliplatin containing adjuvant therapy * Interstitial lung disease with ongoing signs and symptoms at the time of informed consent