NCT05116683

ATX-101 in Advanced Dedifferentiated Liposarcoma and Leiomyosarcoma

A Phase II Study, With a Safety lead-in, to Evaluate ATX-101, a Peptide Drug Targeting PCNA, in Advanced Dedifferentiated Liposarcoma and Leiomyosarcoma

• Status: Terminated
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 4 (actual)
• Sponsor: Benjamin Izar · Academic / Other
• Sex: All
• Age: 18 Years – 99 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study is to evaluate the effectiveness of a new investigational drug, ATX-101, for the treatment of dedifferentiated liposarcoma (LPS) and leiomyosarcoma (LMS). ATX-101 is an intravenous (IV) drug which blocks the interaction of a protein called PCNA with a number of "stress response" proteins. These interactions are thought to be important for cancer cell survival and growth. ATX-101 may disrupt these interactions and therefore help treat the cancer. In this study, all patients will receive the same treatment. Most of the exams, tests, and procedures are part of the usual approach to medical care for this condition. However, some additional tests or procedures may be performed, and other tests may be performed more frequently than usual.

Detailed description

ATX-101 is a small molecule peptide comprised of a novel human proliferating cell nuclear antigen (PCNA) interacting motif termed APIM coupled to cellular and nuclear delivery domains. PCNA interacts with many cellular proteins and exerts pleiotropic effects in the cancer cell. Proteins that bind to PCNA via APIM are especially important in the cellular stress and DNA damage responses, as well as intracellular signaling, apoptosis, metabolism and anti-tumor immunity. In preclinical studies, ATX-101 demonstrated single-agent activity and potentiated other cytotoxic and targeted agents across multiple cancer models in vitro and in vivo, including LMS and LPS. ATX-101 is currently being evaluated in a phase 1 safety and pharmacokinetic study in solid tumors using a 3 + 3 dose escalation design. As of 10/29/2020, ATX-101 has been evaluated across dose levels of 20 mg/m2 - 60 mg/m2 IV weekly. Although no maximum tolerated dose (MTD) was reached, after review of the available safety data, the RP2D was determined to be 60 mg/m2 IV weekly, with no plans to dose escalate further. ATX-101 has been well tolerated, with no grade 3 or higher adverse events (AEs) observed during the phase 1 study. Common AEs include grade 1/2 infusion related reactions (which have been easily managed with supportive care), mild fatigue and diarrhea. In this study, ATX-101 demonstrated encouraging activity as prolonged disease stabilization in patients with progressive, heavily pre-treated malignancies.

Conditions

• Leiomyosarcoma
• Liposarcoma

Interventions

Type	Name	Description
DRUG	ATX-101	Patients will be given ATX-101 at 60 mg/m2 IV weekly in continuous 21 day cycles.

Timeline

• Start date: 2022-01-11
• Primary completion: 2022-10-27
• Completion: 2022-10-27
• First posted: 2021-11-11
• Last updated: 2023-12-06
• Results posted: 2023-12-06

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study