ALRN-6924 and Paclitaxel in Treating Patients With Advanced, Metastatic, or Unresectable Solid Tumors

Primary Objectives: * Determine the dose-limiting toxicities (DLT) and the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) of ALRN-6924 in combination with paclitaxel in adult patients with advanced or metastatic solid tumors with wild-type (WT) TP53. * Evaluate the safety and tolerability of ALRN-6924 in combination with paclitaxel in patients with advanced or metastatic WT TP53 solid tumors. Secondary Objective: • Evaluate the anti-tumor activity of ALRN-6924 in combination with paclitaxel in solid tumors (in dose escalation) and hormone-receptor positive breast cancer (in expansion). Exploratory objective: * Assess predictive and pharmacodynamic (PD) markers of response. * Assess the effects of ALRN-6924 and paclitaxel on cell proliferation and apoptosis. * Assess the effects of ALRN-6924 and paclitaxel on cell-free DNA (cfDNA) dynamics and macrophage inhibitory cytokine-1 (MIC-1) OUTLINE: This is a dose-escalation study of MDM2/MDMX inhibitor ALRN-6924. Patients receive paclitaxel intravenously (IV) over 1 hour and MDM2/MDMX inhibitor ALRN-6924 IV over 1 hour on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 2 months for 1 year and then every 3 months thereafter.