Treatment with the investigational agent SY-2101 has begun in a phase 3 clinical trial of patients with newly-diagnosed acute promyelocytic leukemia.
The first patient with newly diagnosed acute promyelocytic leukemia (APL) has been dosed with SY-2101, initiating an investigation of the pharmacokinetics, safety, and tolerability of the agent in a phase 3 clinical trial, according to a press release issued by Syros Pharmaceuticals.1
SY-2101 is a novel oral form of arsenic trioxide (ATO). In previous studies, the agent administered once daily was well-tolerated in patients and showed similarity to intravenous (IV) ATO, the standard of care option, in terms of oral bioavailability and PK exposure.
"The current standard of care cures most patients but is tremendously burdensome, requiring regular and lengthy infusions of an IV formulation of ATO over nearly a yearlong course of treatment," said Farhad Ravandi, MD, professor of medicine, chief of Section of Acute Myeloid Leukemia, Department of Leukemia at The University of Texas MD Anderson Cancer Center, in a press release. "An oral form of ATO that offers similar efficacy while dramatically reducing the treatment burden would represent a major advance for APL patients. The preliminary phase 1 data for SY-2101 are very promising, and I look forward to its continued advancement in the current and future studies."
Approximately 24 patients with APL will be enrolled in the 3-part study. In part 1, patients will be given a single dose of IV ATP followed by a single dose of SY-2101 administered 1 week later, which will then be followed by another single dose of SY-2101 a week later. Blood tests and safety evaluation will be performed following each dose of the study drugs.2
In part 2, patients only received the standard dose of IV ATO will blood test and safety assessment following. Then, in part 3, patients who had a molecular response to therapy will receive SY-2101 instead of IV ATO during the fourths consolidation therapy cycle, which will be followed by blood draw for testing and a safety assessment.
To be eligible for inclusion, patients are required to have low risk APL that is characterized by t(15;17) translocation or PML/RARA gene expression positivity. All patients must have received ATO plus ATRA induction therapy and must have had consolidation therapy or are eligible to received consolidation therapy. Those enrolled must also be able to tolerable a full dose of ATO, be in morphological complete remission following induction therapy, and must not be pregnant.
The study will exclude individuals who are not eligible for consolidation, are being treated for a non-APL malignancy, have an active, life-threatening, or uncontrolled systemic infection, are immunocompromised, or those who are positive for hepatitis B or C, or human immunodeficiency virus. In the case that a patient has undergone surgery, they must be adequately recovered 4 weeks prior to the start of the study. Patients who have received other investigational agents within 4 weeks of screening in the study are ineligible to enroll as are patients with hypersensitivity to arsenic and those who developed grade 3 or higher non-hemaotlogic toxicities associated with ATO treatment.
"We are thrilled to now be dosing patients in our dose confirmation study of SY-2101," said David A. Roth, MD, chief medical officer at Syros, in a press release.1 "We believe SY-2101 could quickly become the new standard of care for APL by offering patients similar efficacy with a substantially more accessible and convenient therapy. We plan to move swiftly from our dose confirmation study into a Phase 3 trial next year, with the goal of filing a new drug application in 2024."
1. Syros announces first patient in dose confirmation study of SY-2101, a novel oral form of arsenic trioxide, in acute promyelocytic leukemia. News release. Syros Pharmaceuticals. September 29, 2021. Accessed September 29, 2021.
2. A study for oral SY-2101 for participants with acute promyelocytic leukemia. Clinicaltrials.gov. Accessed October 1, 2021.