Annamycin for STS Lung Metastases Shows Clinical Activity


Fifty percent of patients in the first 2 cohorts of an early-phase study experienced stable disease on annamycin, and no dose-limiting toxicities were observed.

Annamycin for soft tissue sarcoma (STS) lung metastases showed clinical activity and a tolerable safety profile, according to interim results of a phase 1b/2 clinical trial of the agent reported in a press release by Moleculin Biotech, Inc.

According to results, 50% of patients in the 210 mg/m2 cohort and the 270 mg/m2 cohort experienced clinical activity, as defined as stable disease and/or better through 4 months or more of treatment. Additionally, no dose-limiting toxicities have been observed.

Annamycin is a next-generation anthracycline that has demonstrated a lack of cardiotoxicity in multiple huma clinical trials. In animal trials, it has shown to accumulate in the lungs at up to 30-fold the level of doxorubicin. It currently holds both fast track and orphan drug designations from the FDA for the treatment of STS lung metastases.

The study (NCT04887298) has an estimated enrollment of 55 participants and an estimated completion date of May 2024. The primary end point is dose limiting toxicity. Secondary end points include efficacy of the agent and area under the plasma concentration versus time curve.

During the study, patients received a 2-hour intravenous infusion of annamycin on day 1 followed by 20 days off. Treatment is continued until disease progression or unacceptable toxicity. Tumor response is monitored every 6 weeks. Dose levels of 210 mg/m2, 270 mg/m2, and 330 mg/m2 were tested.

In the 210 mg/m2 cohort, 2 patients had stable disease up to 6 cycles, but both discontinued due to progressive disease. One patient discontinued after the first cycle. In the 270 mg/m2 cohort, one patient experienced a partial response. However, they discontinued to undergo surgical resection. In the 330 mg/m2cohort, 1 patient received 1 cycle of therapy, and no dose-limiting toxicities were observed. However, treatment was discontinued after 2 cycles due to progressive disease.

"Even though this is still early in the Phase 1b portion of the trial, the data continue to be encouraging. Three of the six patients in the first two cohorts reached four or more months with stable disease or better. In a patient population where the median progression-free survival is approximately 1.61 months, we believe Annamycin has the potential to bring a new and effective treatment option to patients with this significant unmet need," said Walter Klemp, chairman and chief executive officer of Moleculin, in a press release.

In order to participate in the study, patients must have a confirmed diagnosis of STS and documented lung metastases, have measurable disease, an estimated life expectancy greater than 3 months, an ECOG score of 2 or less, and be at least 18 years of age. Patients with left ventricle ejection fraction, a clinically relevant serious comorbid medical condition, is not using adequate contraception, or a known allergy to the study drug is not eligible to participate.

"Consistent with our earlier and ongoing acute myeloid leukemia trials to date, we continue to see a complete absence of cardiotoxicity in this STS trial," said Klemp. "We continue to emphasize this point because, even though anthracyclines are considered a cornerstone chemotherapy for many types of cancer including STS lung metastases, all currently approved anthracyclines are significantly cardiotoxic. Annamycin was designed to overcome this problem and we believe it has the potential to become the first non-cardiotoxic anthracycline approved for use. This could not only reduce the risk of many current anthracycline treatment regimens, but it could also enable longer treatment periods without cardiac risk."

Moleculin announces preliminary third cohort interim data in phase 1b/2 clinical trial of annamycin for the treatment of soft tissue sarcoma lung metastases. News release. Moleculin. December 27, 2021. Accessed January 3, 2022.
Study of liposomal annamycin for the treatment of subjects with soft-tissue sarcomas (STS) with pulmonary metastases. Accessed January 3, 2022.

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