Liposomal Annamycin Plus Cytarabine Generates Responses in AML

Treatment with the combination of liposomal annamycin and cytarabine (AnnAraC) elicited responses in patients with acute myeloid leukemia (AML), particularly in a cohort of patients receiving second-line therapy, according to interim data from the phase 1b/2 MB-106 trial (NCT05319587).¹

Findings showed that in all evaluable patients (n = 18), AnnAraC produced a composite complete response (CRc) rate of 39%, including a CR rate of 33% and a CR with incomplete hematologic recovery (CRi) rate of 6%. Additionally, 2 patients achieved a partial response (PR).

Notably, evaluable patients treated in the second line (n = 10) experienced a CRc rate of 60%, including CR and CRi rates of 50% and 10%, respectively. One patient had a PR.

In the first-line setting, evaluable patients (n = 2) had a CRc rate of 50%, with 1 patient achieving a CR.

“We remain highly encouraged by the positive data seen to date in our phase 1B/2 AnnAraC trial for AML,” Walter Klemp, chairman and chief executive officer of Moleculin Biotech, stated in a news release. “With a CRc rate of 60% as second-line therapy and with 50% of those being full CRs, AnnAraC has the potential to offer [patients in the] second line a viable alternative, regardless of prior treatments or mutations. Importantly, we recently visited prominent key opinion leaders in Europe and the United Stated. Without exception, they each believe there remains a significant unmet need for second-line AML therapies, that our results in [patients in the] second line are significant, and that, if approved, they would use annamycin in their practice. We are seeing genuine enthusiasm for how annamycin might change the paradigm.”

The multicenter, open-label, dose-escalation MB-106 trial is enrolling patients at least 18 years of age with pathologically confirmed AML per World Health Organization classification, defined as either a bone marrow aspirate or biopsy, or a complete blood count, that demonstrates myeloblasts at more than 5%. Patients are allowed to be treatment naive or relapsed/refractory after induction therapy with more than 5% bone marrow blasts. An ECOG performance status of 0 to 2, as well as adequate laboratory results, are required.²

Key exclusion criteria include acute promyelocytic leukemia; prior mediastinal radiotherapy; central nervous system involvement; and a left ventricle ejection fraction of less than 50%, valvular heart disease, or severe hypertension.

Enrolled patients are being treated with liposomal annamycin as a 2-hour intravenous infusion once per day for the first 3 days of each 21-day cycle in combination with 2.0 g/mg² of cytarabine for 5 consecutive days during cycle 1.

Safety and determination of the maximum tolerated dose/recommended phase 2 dose are the study’s primary end points. Secondary end points include pharmacokinetics and anti-leukemia activity.

For all enrolled patients across all lines of therapy thus far (n = 20), the median age was 69 years (range, 19-78), and patients received a median of 1 prior line of therapy. Notably, 2 patients from the overall population were not yet evaluable for efficacy.¹

Regarding safety, Moleculin Biotech said among patients treated with liposomal annamycin across multiple studies (n = 82), no signs of cardiotoxicity have been exhibited, and the agent has demonstrated a lower toxicity profile vs traditional intensive therapy.

“Our growing body of data are now propelling our clinical and regulatory strategies toward our next phase of development. We are preparing for an end of phase 2 meeting with FDA and believe following this meeting we will be in a position to commence a pivotal registration study as a second-line therapy in AML before year end,” Klemp concluded.

References

1. Moleculin announces positive interim data in annamycin MB-106 phase 1B/2 AML trial. News release. Moleculin Biotech. March 25, 2024. Accessed March 25, 2024. https://moleculin.com/moleculin-announces-positive-interim-data-in-annamycin-mb-106-phase-1b-2-aml-trial/
2. Study of liposomal annamycin in combination with cytarabine for the treatment of subjects with acute myeloid leukemia (AML). ClinicalTrials.gov. Updated November 18, 2023. Accessed March 25, 2024. https://www.clinicaltrials.gov/study/NCT05319587