Phase 1/2 Trial of Annamycin Plus Cytarabine Doses First Patient With R/R AML

The next-generation anthracycline Annamycin has been administered to the first patient with relapsed/refractory acute myeloid leukemia in combination with cytarabine in a phase 1/2 study.

About the Phase 1/2 Study of Annamycin in Combination With Cytarabine

Trial Name: Phase 1/2 Study of Liposomal Annamycin in Combination With Cytarabine for the Treatment of Subjects With Acute Myeloid Leukemia (AML) That is Refractory to or Relapsed After Induction Therapy Identifier: NCT05319587

Sponsor: Moleculin Biotech, Inc.

Completion Date: April 30, 2025

The first patient has been dosed in a phase 1/2 study (NCT05319587) evaluating Annamycin combined with Cytarabine for the treatment of patients with acute myeloid leukemia (AML) who are refractory to, or relapsed after, induction therapy, according to Moleculin Biotech, Inc.1

Annamycin is a next-generation anthracycline designed to be non-cardiotoxic. In preclinical models, the agent has demonstrated that it can accumulate in the lungs at up to 30-fold the level of doxorubicin.

Annamycin also has shown to have the ability to avoid the multidrug resistance mechanisms that typically limit the efficacy of doxorubicin and other currently prescribed anthracyclines. Currently, Annamycin is being developed for the treatment of patients with relapsed/refractory AML and soft tissue sarcoma.

"We continue to be highly encouraged by the data demonstrated from the successfully concluded Annamycin single agent trials and the no evidence of cardiotoxicity seen to date. We remain very optimistic in Annamycin's potential to be an important treatment for refractory or relapsed AML in combination with Cytarabine. We are pleased to commence subject dosing in Italy and are continuing our efforts to bring additional sites online and build momentum in enrollment.We are committed to driving the development of Annamycin for the treatment of AML and look forward to continuing our evaluations of Annamycin in combination with Ara-C," commented Walter Klemp, chairman and chief executive officer of Moleculin, in the press release.

This open-label, phase 1/2 trial is looking to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of Annamycin in combination with Cytarabine for the treatment of patients with relapsed/refractory AML. During the phase 1b, dose-escalation portion of the study, a standard 3+3 design will be utilized and a group of 3 patients will be treated with an intravenous infusion of 190-mg/m2 of Annamycin for 3 consecutive days. The dose-escalation will occur based on safety assessments in sequential cohorts of 3 subjects each.2

The primary end point of the study is to evaluate the MTD and RP2D of the combination with secondary end points including pharmacokinetics and anti-leukemic activity.

Patients aged 18 years and older with AML that are refractory to or relapsed after induction therapy, have received no investigational therapy within 4 weeks of the first dose of study treatment, chemotherapy, radiation, or major surgery within 2 weeks prior to first dose of treatment, and who have recovered from toxicities associated with their therapies, unless treatment is indicated as a result of progressive disease, will be included in the study. Additionally, patients must have an ECOG performance status of 0-2, an HCT-CI score of 0-2, and adequate laboratory results. Men and women of childbearing potential must agree to use contraception during the duration of the trial and after discontinuing the study treatment.

This open-label, phase 1/2 MB-106 trial builds on the safety and dosage data that was previously reported in 2 successful and completed phase 1 trials: MB-104 and MB-105. Both studies were conducted in the United States and Europe, respectively.1

In the MB-105 trial, the final cohort of patients with relapsed/refractory AML who were 62-73 years of age had an overall response rate (ORR) of 80%. There was 1 complete response with incomplete recovery of peripheral blood count and 3 partial responses observed.

The FDA has already granted Annamycin fast track and orphan drug status for the treatment of soft tissue sarcoma lung metastases and the treatment of relapsed or refractory AML.

1. Moleculin announces dosing of first subject in Italy for phase 1/2 trial evaluating annamycin in combination with cytarabine (Ara-C) for the treatment of acute myeloid leukemia (AML). News release. Moleculin Biotech, Inc. March 1, 2023. Accessed March 30, 2023.
2. Study of liposomal annamycin in combination with cytarabine for the treatment of subjects with acute myeloid leukemia (AML). Updated February 1, 2023. Accessed March 30, 2023.

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