A Phase 1b Dose-escalation Study to Assess the Safety, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of PLX2853 in Subjects With Relapsed or Refractory Acute Myeloid Leukemia or High-risk Myelodysplastic Syndrome
Overview
- Phase
- Phase 1
- Intervention
- PLX2853
- Conditions
- Relapsed Acute Myeloid Leukemia (AML)
- Sponsor
- Opna Bio LLC
- Enrollment
- 22
- Locations
- 6
- Primary Endpoint
- Area under the concentration-time curve (AUC) of PLX2853
- Status
- Completed
- Last Updated
- 4 years ago
Overview
Brief Summary
The purpose of this research study is to evaluate safety, pharmacokinetics, pharmacodynamics and preliminary efficacy of the investigational drug PLX2853 in subjects with Relapsed or Refractory Acute Myeloid Leukemia or High-risk Myelodysplastic Syndrome
Investigators
Eligibility Criteria
Inclusion Criteria
- •Confirmed diagnosis of one of the following myeloid malignancies, based on the 2016 revision of the World Health Organization classification:
- •A. Relapsed or refractory AML.
- •I. Subjects must have received no more than 3 prior induction therapies and have no standard therapeutic option that is expected to result in a clinical benefit.
- •B. Relapsed or refractory MDS.
- •I. Subjects must have high-risk disease (intermediate or greater disease according to the revised International Prognostic Scoring System \[IPSS-R\]).
- •II. Subjects must have received no more than 3 prior therapies, 1 of which must have included a hypomethylating agent such as azacytidine or decitabine.
- •III. Subjects must have no standard therapeutic option that is expected to result in a clinical benefit.
- •Age ≥18 years.
- •Eastern Cooperative Oncology Group (ECOG) performance status of ≤
- •Life expectancy of ≥3 months in the judgment of the investigator.
Exclusion Criteria
- •Prior treatment with a bromodomain inhibitor.
- •Any one of the following therapies:
- •A. Stem cell transplantation within 90 days of study drug initiation;
- •B. Active immunosuppressive therapy for graft-versus-host disease (GVHD);
- •C. GVHD prophylaxis within 2 weeks of study drug initiation.
- •Known uncontrolled fungal, bacterial, and/or viral infection ≥Grade
- •Uncontrolled autoimmune hemolytic anemia or immune thrombocytopenia.
- •Active symptomatic central nervous system involvement of AML. (Individuals who have had leptomeningeal disease that was effectively treated are eligible.)
- •A diagnosis of acute promyelocytic leukemia or chronic myeloid leukemia in blast crisis.
- •Known or suspected allergy to the study drug or any agent given in association with this trial.
Arms & Interventions
PLX2853
Approximately 30 subjects will be enrolled as part of dose escalation to identify the MTD/RP2D of PLX2853. Up to 6 additional subjects may be enrolled at the MTD/RP2D to further characterize the PK and PDy of PLX2853.
Intervention: PLX2853
Outcomes
Primary Outcomes
Area under the concentration-time curve (AUC) of PLX2853
Time Frame: From first dose of PLX2853 up to 30 days after end of treatment
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
Time Frame: First dose of study drug through at least 30 days after end of treatment
Half life (t1/2) of PLX2853
Time Frame: From first dose of PLX2853 up to 30 days after end of treatment
Terminal elimination rate constant (Kel)
Time Frame: From first dose of PLX2853 up to 30 days after end of treatment
Maximum observed concentration (Cmax) of PLX2853
Time Frame: From first dose of PLX2853 up to 30 days after end of treatment
Number of participants who experience dose limiting toxicity as defined in the protocol
Time Frame: up to 18 months
Dose escalation will be guided by a modified continuous reassessment method (mCRM) using a Bayesian logistic regression model that follows the escalation with overdose control (EWOC) principle. In this method, a decision to escalate to the next dose level is based on a review of all subjects who have completed the DLT observation period.
Time to peak concentration (Tmax) of PLX2853
Time Frame: From first dose of PLX2853 up to 30 days after end of treatment
Secondary Outcomes
- Duration of response (DOR)(DOR defined as the time from the initial objective response to disease progression or death, whichever occurs first, assessed up to 18 months)
- Overall response rate (ORR)(From the first dose of study drug until the date of documented response to treatment, assessed up to 18 months)
- Overall complete remission (OCR) rate(From the first dose of study drug until the date of documented best response to treatment, assessed up to 18 months)
- Event-free survival (EFS)(EFS time is defined as the time from the first dose of PLX2853 to treatment failure, relapse after initial response or death from any cause, assessed up to 18 months.)
- Progression-free survival (PFS)(PFS time is defined as the time from the first dose of PLX2853 to disease progression or death, whichever occurs first, assessed up to 18 months.)
- Overall survival (OS)(From the first dose of study drug until the date of death from any cause, assessed up to 18 months.)