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.