In the dose de-escalation cohort: subjects must have evaluable disease
For escalation, subjects must have a pathologically confirmed diagnosis of PPV-MF, PET-MF, or PMF as per the European Hematology Association (EHA) or World Health Organization (WHO) diagnostic criteria (note that all diagnoses must include the presence of at least grade  marrow fibrosis according to the European Consensus on Grading of Bone Marrow Fibrosis as well as intermediate-, intermediate-, or high risk disease according to the International Working Group for Research and Treatment of Myelofibrosis (IWG-MRT) Dynamic International Prognostic Scoring System; patients with PV may enter the trial if they meet the labeled indication for ruxolitinib (eg hydroxyurea resistant or refractory)\r\n* Escalation Stage : patients who have not achieved normalization of splenomegaly, who have ongoing disease related symptoms (as defined by Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score [MPN-SAF TSS]), or blood counts with at least  weeks of therapy with a steady dose of ruxolitinib\r\n* Escalation Stage : patients who have not yet received therapy with any JAK-STAT inhibitory agents or patients on at least  weeks of a steady dose of ruxolitinib (patients with exposure to other JAK-STAT inhibitory agents are not eligible); after discussion with the study chair or designee, patients with suboptimal response on at least  weeks of a steady dose of ruxolitinib may be allowed to de-escalate ruxolitinib therapy in order to enter a safety cohort which is enrolling patients at a lower dose; patients must receive the lower dose of ruxolitinib for at least  consecutive days without event before adding TGR-; if the patient completed screening evaluation including bone marrow biopsy/aspirate prior to ruxolitinib de-escalation, it need not be repeated after de-escalation provided that all evaluation occurred within  days prior to the first dose of TGR-
Dose Escalation (Segment ):  - 
NOTE: the first subject in the first dose cohort must be >=  years of age if an adult has not been treated at that dose cohort on the companion Stanford protocol Phase  Dose Escalation Study of CD/CD Chimeric Antigen Receptor (CAR) T Cells in Adults with Recurrent or Refractory B Cell Malignancies and undergone safety evaluation at day  without evidence of dose limiting toxicity (DLT)
ENROLLMENT TO THE DOSE ESCALATION, EXPANSION AND PART II: Part I dose escalation: Participants are required to have measurable disease per RECIST . within  weeks of study entry
ENROLLMENT TO THE DOSE ESCALATION, EXPANSION AND PART II: Part I dose escalation: Concurrent use of proton-pump inhibitors (PPIs) is prohibited
Extrahepatic spread; for the dose escalation, regional lymphadenopathy and subcentimeter pulmonary nodules are allowed.
Phase I Dose Escalation:
Phase  (dose escalation) subjects must have either:
Bone only patients during dose escalation portion.
INCLUSION CRITERIA FOR DOSE ESCALATION COHORT
EXCLUSION CRITERIA FOR DOSE ESCALATION COHORT
Dose escalation only: known grade  toxicity probably or definitely attributed to past irinotecan treatment
Patients in Cohort  (dose escalation) may have any level of expression
DOSE ESCALATION COHORT: Prior receipt of docetaxel is permitted
DOSE ESCALATION COHORT: Measurable disease is not required for enrollment
known bone marrow involvement due to underlying malignant disease, in dose-escalation phase only
Phase Ia (dose-escalation)
For the dose escalation phase, the trial population will be limited to solid tumor types
During the Dose Escalation Phase: only adult patients with active disease failing standard therapy
Patients with CEA plasma levels >  ng/mL are excluded during dose escalation, but may be included after the MTD is determined.
For the dose escalation cohort, patients may have received any number of prior therapies
Dose Escalation cohort only: Willingness to participate in the SPECT/CT imaging as required by the protocol
DOSE ESCALATION COHORT: Prior treatment with at least one line of systemic therapy
DOSE ESCALATION COHORT: Subjects with advanced and unresectable solid tumor who progressed on at least one line of systemic therapy, and no approved therapy or standard therapy with demonstrated clinical benefit exists; and all subjects with TM mutation positive NSCLC have progressed on osimertinib\r\n* Note: disease measurability is not required for dose escalation
DOSE ESCALATION COHORT: Leukocytes ? ,/mcL
DOSE ESCALATION COHORT: Platelets ? ,/mcL
DOSE ESCALATION COHORT: Hemoglobin ?  g/dL
DOSE ESCALATION COHORT: Brain metastases: symptomatic, unstable, or disease requiring use of steroid treatment
DOSE ESCALATION COHORT: Pregnant or nursing
For Dose Escalation:
For Dose Escalation:
For Dose Escalation (Part A): Have measurable or nonmeasurable disease.
For dose escalation part: Patients with MCL at high risk for tumor lysis syndrome
Women who are pregnant or lactating Dose-Escalation Portion of the Study:
For Japan Escalation - the same as the global escalation I/E criteria except patients must be EGFR mutation positive
Dose Escalation
Subjects must have an advanced hematologic malignancy including: Phase / Dose escalation:
Patients may have not received treatment for  days before the first day of the study protocol (dose escalation only)
Dose-Escalation Stage:
Safety Cohort (Dose Escalation)
Previous treatment for MDS or MPN for dose escalation cohorts
Biopsy proven HER negative metastatic breast cancer (dose escalation portion and MTD expansion portion) or advanced solid tumor (dose escalation portion).
DOSE ESCALATION COHORT:
DOSE ESCALATION COHORT EXCLUSION:
DOSE ESCALATION COHORT: patients must have had at least one prior therapy
For dose escalation monotherapy: CLL, HL, NHL, MM
Eligibility based on prior treatment with CIT depends on the mechanistic class of the drug and the cohort for which the participant is being considered, as described below. In addition, all criteria pertaining to adverse events attributed to prior cancer therapies must be met All Cohorts (Dose-Escalation in Phase a and Dose-Escalation, Backfill, and Expansion in Phase b):
Dose Escalation Phase: Patients have exhausted, or be deemed to not benefit from, further conventional therapy and have evidence of progressive disease on study entry.
Part A- Diagnosed with advanced and/or metastatic cancer during dose escalation
There is no line limit for the dose escalation cohort and the dose expansion cohort
Dose escalation phase prior systemic treatment requirements:
Participants in the dose escalation cohort must have a serum albumin of ? . g/dL at screening.
Dose Escalation Segment
Part , Dose Escalation: tumor tissue
Phase  trials in dose escalation