A phase 1b/2 clinical trial aims to evaluate the safety of lanraplenib plus gilteritinib in patients with relapsed/refractory FLT3-mutated acute myeloid leukemia.
The first patient has been dosed in the phase 1b/2 clinical trial (NCT05028751) of lanraplenib (Lanra) in combination with gilteritinib in patients with relapsed/refractory FLT3-mutated acute myeloid leukemia (AML), according to Kronos Bio, Inc.1
The multi-center, open-label, dose-escalation, clinical trial will evaluate patients with relapsed/refractory FLT3-mutated AML to examine the safety of lanraplenib and the FLT3 inhibitor gilteritinib.2
Trial Name: A Study to Evaluate Lanraplenib (LANRA) in Combination With Gilteritinib in Participants With FLT3-mutated Relapsed or Refractory Acute Myeloid Leukemia (AML)
ClinicalTrials.gov Indentifier: NCT05028751
Completion Date: October 2024
Recruitment Status: Recruiting
Sponsor: Kronos Bio
Recruitment Contact: Director of Clinical Operations 650-484-1583 clinicaltrials@kronosbio.com
Lanraplenib is a next-generation selective inhibitor targeting spleen tyrosine kinase being evaluated as a treatment option for patients with relapsed/refractory FLT3-mutated AML. Previously, lanraplenib has been examined in more than 250 patients with autoimmune diseases and preclinical studies have shown lanraplenib to have anti-leukemic activity against NPM1-mutated and FLT3-mutated AML samples.
“The initiation of this study is an important first step as we advance lanraplenib for patients with certain genetically defined types of AML,” said Jorge DiMartino, MD, PhD, chief medical officer, executive vice president of Clinical Development at Kronos Bio, said in a press release. “Our long-term vision is to develop lanraplenib as a cornerstone of targeted regimens for these patients, allowing us to potentially reach as many as two-thirds of patients with AML. Today’s announcement represents important progress toward that goal.”
The trial is being conducted in 2 stages with stage 1 consisting of the dose-escalation portion and stage 2 as the expansion stage.
In the first stage, investigators aim to evaluate the initial safety, pharmacokinetic and anti-leukemic activity of escalating once-daily doses of lanraplenib when combined with the standard approved dose of gilteritinib. Additionally, the dose-escalation portion of the trial will assess the FLT3 measurable residual disease (MRD) negative rate in patients who achieve a complete response (CR) as well as determine the predictive value of a number of biomarkers that may correlate with clinical outcomes.
After the recommended dose of lanraplenib is determined, the expansion portion of the trial aims to enroll 30 participants and will further assess the safety of lanraplenib and its anti-leukemic activity as measured by composite CR rate and duration of response.
Enrollment in the trial is open to adult patients aged 18 years and older with AML who have had at least 1 prior line of therapy. Other requirements include FLT3-mutated disease documented in a local reference laboratory, an ECOG performance status of 0, 1, or 2, adequate hepatic and renal function, prothrombin time, activated partial thromboplastin time, and international normalized ratio ≤1.5x upper limit of normal unless receiving therapeutic anticoagulation, and left ventricular ejection fraction ≥50% confirmed by echocardiogram or multi-gated acquisition scan. Women of child-bearing potential must have a negative serum ß-human chorionic gonadotropin test.
The primary end point for part 1 and 2 of the trial is the number of participants who experience a treatment-emergent adverse event and/or a dose-limiting toxicity (DLT) for lanraplenib. Other primary end points for part 1 include to determine the maximum tolerated dose of lanraplenib and its recommended phase 2 dose.
Secondary end points for part 1 consist of maximal plasma concentration, time to maximal plasma concentration, area under the plasma concentration, and time curve from hour 0 to the last measurable time point. For parts 1 and 2, other secondary end points are composite CR rate, composite CR rate with partial hematologic recovery, duration of response, event-free survival, and overall survival.
The trial is actively recruiting in California, Georgia, Texas, and Wisconsin and has an estimated study completion date of October 2024.
