Patients with acute myeloid leukemia given annamycin demonstrated tolerable safety and preliminary efficacy with the agent, according to topline results from a phase 1/2 study.
Treatment with annamycin in patients with acute myeloid leukemia (AML) showed tolerable safety and preliminary efficacy with an objective response rate of 80%, according to topline results from a phase 1/2 study (MB-105; NCT03388749).1
Annamycin has an FDA fast track designation for the treatment of relapsed or refractory AML as well as an orphan drug designation. The agent also has fast track and orphan drug designations for the treatment of soft tissue sarcoma lung metastases.
“We are very pleased with these topline results, both in terms of safety and the initial data suggesting efficacy, especially since these patients were relapsed or refractory,” said Walter Klemp, chairman and chief executive officer of Moleculin, in a press release, “Given the recently published research showing that annamycin in combination with cytarabine substantially outperformed annamycin as a single agent in an aggressive AML mouse model, these topline results are encouraging as we continue to develop annamycin in combination with cytarabine for the treatment of AML. Having previously announced the start of our open label MB-106 trial of annamycin in combination with cytarabine for the treatment of AML phase 1/2 trial in Poland and Italy, we are optimistic about annamycin’s potential for the treatment of AML, as we continue to gather the data that ultimately will be necessary to support approval.”
The open-label, single-arm study enrolled 20 subjects who were aged 60 years or older with relapsed or refractory AML. The patients have a median of 4 prior lines of therapy (range 1-18).
The study followed a 3 + 3 design in which patients were treated with a starting dose of 120 mg/m2/day for 30 days, then the dose was escalated. After cohort 0 began with the starting dose of annamycin, treatment at 30-mg/m2/day occurred in increment for cohorts 1 through 5 until patients were enrolled at the 240 mg dose level.1,2
The study is investigating safety determined by the maximum-tolerated dose and the recommended phase 2 dose (RP2D) of annamycin. In February for 2022, the RP2D was determined to 240 mg/m2. The secondary end points of the study include pharmacokinetics and anti-leukemic activity.
Toplines results showed that 1 patient experienced a complete response with incomplete recovery of peripheral blood count, and 3 patients achieved partial response. In terms of safety, the common adverse events were hematologic toxicities, including neutropenia, thrombocytopenia, and anemia.1
Regarding the safety findings, Klemp stated, “We also are encouraged by the absence of cardiotoxicity with annamycin to date. This is particularly relevant in light of a recently published retrospective study showing that the incidence of heart failure more than doubles for cancer patients treated with anthracyclines compared to cancer patients not receiving anthracyclines. annamycin was designed to be non-cardiotoxic, and we believe the initial safety data, if replicated along with efficacy data as our development work continues, suggest an opportunity for annamycin to become a preferred anthracycline treatment for AML and other indications.”