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)

2.1. Hypothesis * Single agent pacritinib is effective in disease control of patients with 1q21.3 amplified solid tumors * Single agent pacritinib is safe in patients with 1q21.3 amplified solid tumors * Treatment with pacritinib will decrease plasma cfDNA copy number ratio of 1q21.3 in patients with 1q21.3 amplified solid tumors * Plasma cfDNA copy number ratio of 1q21.3 will correlate with serial radiological findings in patients with 1q21.3 amplified solid tumors 2.2. Primary Objectives • To determine the proportion of patients with 1q21.3 amplified breast cancer (primary population: Cohort A) who remain progression-free at 4 months after treatment with pacritinib 2.3. Secondary Objectives * To determine the safety and tolerability of pacritinib in patients with treatment refractory solid tumors * To determine the RP2D of pacritinib in patients with treatment refractory solid tumors * To evaluate disease response from pacritinib by RECIST criteria version 1.1 and tumor markers * To determine the proportion of patients with 1q21.3 amplified treatment refractory solid tumors excluding (exploratory population: Cohort B) who remain progression-free at 4 months after treatment with pacritinib 2.4. Exploratory Objectives * To determine pharmacokinetic (PK) parameters including Cmax/min and steady state concentrations of pacritinib through serial plasma sampling * To determine pharmacodynamics (PD) parameters including highly sensitive C-reactive protein (CRP), HbA1c, changes in cytokine levels and plasma cfDNA levels of copy number ratio of 1q21.3 * Correlation of plasma cfDNA levels of copy number ratio of 1q21.3 with radiological findings determined by RECIST criteria 1.1 and tumor markers