NCT03725436

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

A Phase 1b Study of ALRN-6924 in Combination With Paclitaxel in Wild-Type TP53 Advanced or Metastatic Solid Tumors Including Estrogen-Receptor Positive Breast Cancer

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 28 (actual)
• Sponsor: M.D. Anderson Cancer Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase Ib trial studies the side effects and best dose of ALRN-6924 when given together with paclitaxel in treating patients with solid tumors that have spread to other places in the body or cannot be removed by surgery. Drugs used in chemotherapy, such as ALRN-6924 and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.

Detailed description

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.

Conditions

• Advanced Malignant Solid Neoplasm
• Anatomic Stage III Breast Cancer AJCC v8
• Anatomic Stage IIIA Breast Cancer AJCC v8
• Anatomic Stage IIIB Breast Cancer AJCC v8
• Anatomic Stage IIIC Breast Cancer AJCC v8
• Estrogen Receptor Positive
• HER2/Neu Negative
• Metastatic Malignant Solid Neoplasm
• Prognostic Stage III Breast Cancer AJCC v8
• Prognostic Stage IIIA Breast Cancer AJCC v8
• Prognostic Stage IIIB Breast Cancer AJCC v8
• Prognostic Stage IIIC Breast Cancer AJCC v8
• Recurrent Breast Carcinoma
• TP53 wt Allele
• Unresectable Malignant Solid Neoplasm

Interventions

Type	Name	Description
DRUG	MDM2/MDMX Inhibitor ALRN-6924	Given IV
DRUG	Paclitaxel	Given IV

Timeline

• Start date: 2019-01-24
• Primary completion: 2026-03-11
• Completion: 2026-03-11
• First posted: 2018-10-31
• Last updated: 2026-03-16

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study