A Single Arm, Phase Ib/II Trial of Single Agent Pacritinib in Patients With 1q21.3 Amplified Solid Tumors Enriching for Interleukin-1 Receptor-associated Kinase 1 Pathway Activation (PAIR)

Inclusion Criteria: Patients may be included in the study only if they meet all of the following criteria: * Age \> or = 21 years. * Histological or cytological diagnosis of malignant advanced solid tumors refractory to standard therapy or for which no suitable effective standard therapy exists. o Patients who fit above criteria will be pre-screened for presence of 1q21.3 amplification using a plasma assay based on digital PCR. Patients with tumors that exhibit 1q21.3amplification will be enrolled. Positive 1q21.3 amplification is defined as more than 3 standard deviations above the mean comparing the averaged copy number ratio of 3 genes (TUFT1, S100A8 and S100A7) relative to the reference gene RPP30 measure in sample (13). * ECOG 0-2 * Has measureable or evaluable disease based on RECIST 1.1 criteria * Estimated life expectancy of at least 12 weeks. * Has documented progressive disease from last line of therapy * Has recovered from acute toxicities from prior anti-cancer therapies * Adequate organ function including the following: * Bone marrow: * Absolute neutrophil (segmented and bands) count (ANC) \> or = 1.5 x 109/L * Platelets \> or = 100 x 109/L * Hemoglobin \> or = 8 x 109/L * Hepatic: * Bilirubin \< or = 1.5 x upper limit of normal (ULN), * ALT or AST \< or = 2.5x ULN, (or \< or = 5 X with liver metastases) * Renal: * Creatinine \< or = 1.5x ULN * Signed informed consent from patient * Able to comply with study-related procedures. * Prior therapy (patients enrolled in phase Ib may be enrolled if they fulfil prior therapy criteria for either Cohort A or Cohort B) * Cohort A only: Has received at least 2 lines of systemic therapy (endocrine or chemotherapy) in the palliative setting. Chemotherapy in an adjuvant setting for which patients relapsed within 6 months of completion can be considered as line(s) of palliative therapy. * Cohort B only: Any number of prior lines of palliative chemotherapy. Exclusion Criteria: Patients will be excluded from the study for any of the following reasons: * Treatment within the last 30 days with any investigational drug. * Concurrent administration of any other tumour therapy, including cytotoxic chemotherapy, hormonal therapy, and immunotherapy. * Major surgery within 28 days of study drug administration. * Active infection that in the opinion of the investigator would compromise the patient's ability to tolerate therapy. * Pregnancy. * Breast feeding. * Serious concomitant disorders that would compromise the safety of the patient or compromise the patient's ability to complete the study, at the discretion of the investigator. * Significant recent bleeding history defined as CTCAE grade 2 or higher within the past 3 months, unless precipitated by an inciting event (e.g. surgery, trauma, injury). * Suboptimal cardiac function, defined by: * Any history of CTCAE grade \> or = 2 non-dysrhythmia cardiac conditions within the last 6 months * New York Heart Association class II, III or IV congestive cardiac failure * Left ventricular ejection fraction of \<45% * QTc prolongation of \>450ms as assessed by ECG or other factors that increase the risk of QT interval prolongation * Second primary malignancy that is clinically detectable at the time of consideration for study enrollment. * Symptomatic brain metastasis. * History of significant neurological or mental disorder, including seizures or dementia. * Unable to comply with study procedures * Systemic treatment with a strong CYP3A4 inhibitor or storn CYP450 inducer within 14 days prior to treatment Day 1 Phase Ib lead-in can recruit patients who fulfil critieria for either Cohort A or Cohort B AND all other inclusion/exclusion criteria