This is a first-in-human, multicenter, open-label, phase 1 study to evaluate the safety, PK, PD and preliminary efficacy of STX-0712 in patients with advanced CMML and AML for whom there are no further treatment options known to confer clinical benefit.
This is an open-label, non-randomized phase 1 trial to assess the safety and preliminary efficacy of STX-0712 in refractory/resistant CMML and relapsed/refractory monocytic or monocytic-predominant AML. The study will be conducted in two parts: Dose Escalation (Part 1) and Dose Expansion (Part 2). Dose Escalation will accrue CMML and AML patients across 2 cohorts using the BOIN adaptive design, followed by Dose Expansion in both cohorts using Simon's 2-Stage Design. Cohort 1 will enroll approximately 3-6 CMML patients at each dose level. After at least two dose levels have been deemed safe in Cohort 1, the Sponsor may decide to open Cohort 2 to enroll AML patients. Approximately 20 patients will be enrolled in each Dose Expansion cohort. All eligible participants will be administered the study drug, STX-0712, as a single intravenous (IV) infusion every 21 days. Patients will remain on study therapy until treatment discontinuation criteria are met.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
105
STX-0712 is IV administered every 21 days until the patient discontinues treatment.
Stanford University
Stanford, California, United States
RECRUITINGMoffitt
Tampa, Florida, United States
RECRUITINGDFCI
Boston, Massachusetts, United States
RECRUITINGMayo Clinic
Rochester, Minnesota, United States
RECRUITINGOHSU
Portland, Oregon, United States
RECRUITINGVanderbilt University
Nashville, Tennessee, United States
NOT_YET_RECRUITINGMD Anderson Cancer Center
Houston, Texas, United States
RECRUITINGTo determine the maximum tolerated dose (MTD) and/or minimum effective dose (MED)
Incidence of dose-limiting toxicity (DLT) events during the DLT monitoring period
Time frame: Until the end of Dose Escalation (approximately 12 months)
To evaluate the overall safety and tolerability of STX-0712
Incidence of adverse events (AEs), characterized overall and by type, seriousness, relationship to study treatment, timing, and severity graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0
Time frame: Until the end of the study (approximately 24 months)
To evaluate the initial anti-tumor activity of STX-0712 in the CMML and AML cohorts
Investigator-assessed overall response rate (ORR) as measured by standard response criteria: For CMML: Proportion of participants achieving complete response (CR), complete cytogenetic remission, partial response (PR), marrow response, and clinical benefit according to the 2015 myelodysplastic/myeloproliferative neoplasms International Working Group (MDS/MPN IWG) criteria. For AML: Proportion of participants achieving complete remission (CR), CR with partial hematologic recovery (CRh), complete remission with incomplete count recovery (CRi), morphological leukemia-free state (MLFS), and PR according to modified European Leukemia Network (ELN) 2022 criteria
Time frame: Until the end of the study (approximately 24 months)
To evaluate the initial anti-tumor activity of STX-0712 in the CMML and AML cohorts
Absolute decrease in peripheral blood monocytes by 50% from baseline in CMML and AML.
Time frame: Until the end of the study (approximately 24 months)
Pharmacokinetics of STX-0712: maximum concentration (Cmax)
maximum concentration (Cmax)
Time frame: Until the end of the study (approximately 24 months)
Pharmacokinetics of STX-0712: time to reach maximum concentration (Tmax)
time to reach maximum concentration (Tmax)
Time frame: Until the end of the study (approximately 24 months)
Pharmacokinetics of STX-0712: area under the curve (AUC)
Area under the curve (AUC)
Time frame: Until the end of the study (approximately 24 months)
Pharmacokinetics of STX-0712: half-life (t½)
Half-life (t½)
Time frame: Until the end of the study (approximately 24 months)
To characterize the PD profile of STX-0712 after single and repeat-dose administration
Decrease in tumor cells following STX-0712 dose STX-0712 single-dose and repeat-dose blood PD biomarkers of target activation
Time frame: Until the end of the study (approximately 24 months)
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