A Phase II Study, With a Safety lead-in, to Evaluate ATX-101, a Peptide Drug Targeting PCNA, in Advanced Dedifferentiated Liposarcoma and Leiomyosarcoma
Overview
- Phase
- Phase 2
- Intervention
- ATX-101
- Conditions
- Leiomyosarcoma
- Sponsor
- Benjamin Izar
- Enrollment
- 4
- Locations
- 1
- Primary Endpoint
- Progression Free Rate (PFR)
- Status
- Terminated
- Last Updated
- 2 years ago
Overview
Brief 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.
Investigators
Benjamin Izar
Assistant Professor, Division of Hematology/Oncology, Department of Medicine
Columbia University
Eligibility Criteria
Inclusion Criteria
- •Histologically confirmed dedifferentiated liposarcoma (LPS) or leiomyosarcoma
- •ATX-101 in Sarcoma Phase II
- •(LMS). Pathology review occurs at the center enrolling the patient on this trial.
- •Disease must be locally advanced and unresectable or metastatic. Disease which may be resected but with an associated level of morbidity deemed unacceptable by the treating clinician is considered eligible.
- •Patients must have measurable disease by RECIST criteria version 1.
- •In addition, the first 10 patients enrolled on the study must have a site of disease amenable to image-guided biopsy at minimal risk or less, and must agree to undergo this biopsy.
- •Patients must evidence of disease progression, either clinically or radiographically, within the 12 weeks prior to study enrollment, as determined by the investigator enrolling the patient on the study.
- •Patients must have been treated with at least one prior systemic regimen for advanced sarcoma: LMS: Anthracycline-based chemotherapy, or gemcitabine/docetaxel. LPS: No specification as to the prior treatment received. Neoadjuvant or adjuvant systemic therapy does not qualify as prior treatment unless completed within 6 months of disease relapse.
- •Patients must be age 18 years or older. Because the safety of ATX-101 in patients less than 18 years of age has not been characterized, children are excluded from the present study.
- •Patients must demonstrate an Eastern Cooperative Oncology Group (ECOG) performance status of ≤
Exclusion Criteria
- Not provided
Arms & Interventions
ATX-101
Patients will be treated with ATX-101 60 mg/m2 IV weekly in continuous 21 day cycles. Patients will receive premedication prior to the ATX-101 infusion to reduce the risk of infusion-related reactions.
Intervention: ATX-101
Outcomes
Primary Outcomes
Progression Free Rate (PFR)
Time Frame: 12 weeks
The study will evaluate the preliminary efficacy of ATX-101 in advanced L-sarcomas (LMS, LPS) by measuring the PFR (progression free rate) at 12 weeks (PFR12). Progression evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm (the appearance of one or more new lesions is also considered progression).
Secondary Outcomes
- Objective Response Rate (ORR)(Up to approximately 7 months)
- Number of Adverse Events(Up to approximately 7 months)
- Duration of the Response(Up to approximately 7 months)
- Median Progression Free Survival (PFS)(Up to approximately 5 months)
- Median Overall Survival (OS)(Up to approximately 7 months)