Study of AMXT 1501 and DFMO in Combination With Standard Therapies in Advanced Solid Tumors
brief summary
This study will evaluate the safety, tolerability, and preliminary effectiveness of AMXT 1501 and DFMO when combined with standard treatments for advanced solid tumors. The trial includes two groups: * Cohort 1: Patients with ER+ / HER2- breast cancer receiving fulvestrant and capivasertib * Cohort 2: Patients with unresectable or metastatic cutaneous melanoma receiving pembrolizumab The Phase 1b portion will find the recommended Phase 2 dose (RP2D). The Phase 2 portion will further evaluate clinical activity at the RP2D using response criteria for solid tumors (RECIST 1.1). The study will also evaluate pharmacokinetics, pharmacodynamics, disease control, and overall safety.
detailed description
This is a multicenter, open-label Phase 1b/2 clinical trial evaluating the combination of oral AMXT 1501 and oral DFMO with standard of care (SOC) therapies in patients with advanced solid tumors who have progressed after prior therapy.
AMXT 1501 is a polyamine transport inhibitor, and DFMO is an inhibitor of polyamine biosynthesis. Together, they are designed to reduce tumor polyamines and potentially improve tumor response to standard cancer treatments. Preclinical and early clinical studies suggest that dual polyamine blockade may reduce tumor growth and reverse tumor-induced immunosuppression.
Cohort 1: ER+ / HER2- Breast Cancer
Patients receive AMXT 1501 + DFMO in combination with:
Fulvestrant 500 mg IM
Capivasertib 400 mg PO BID (4 days on, 3 days off)
Cohort 2: Unresectable or Metastatic Cutaneous Melanoma
Patients receive AMXT 1501 + DFMO in combination with:
Pembrolizumab 200 mg IV every 3 weeks
Phase 1b (Safety Run-In)
The primary objective is to evaluate safety, tolerability, dose-limiting toxicities (DLTs), and to identify the recommended Phase 2 dose (RP2D). A standard 3+3 dose-escalation design is used.
Phase 2 (Dose Expansion)
The study evaluates the efficacy of the combination regimens using:
Objective response rate (ORR)
Duration of response (DOR)
Disease control rate (DCR)
Progression-free survival (PFS)
Overall survival (OS)
Pharmacokinetics, pharmacodynamics, and biomarker analyses (including tumor biopsies) will also be conducted.
Up to approximately 92 patients will be enrolled across the two cohorts.
official title
A Phase 1b/2 Trial Investigating the Safety and Efficacy of Oral AMXT 1501 and Oral DFMO in Combination With Standard of Care in Patients With Advanced Solid Tumors Who Progressed After Prior Therapies