Annamycin Drives Clinical Benefit in Soft Tissue Sarcoma Lung Metastases

Soft Tissue Sarcoma |
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The next-generation anthracycline analog annamycin demonstrated clinical activity and a favorable safety profile in patients with soft tissue sarcoma and lung metastases, according to updated findings from the phase 1b/2 MB-107 trial (NCT04887298).1

In the study population evaluable for efficacy (n = 36), the clinical benefit rate (CBR) was 59.4%, comprising 18 patients who achieved stable disease and 1 patient who experienced a partial response. The median progression-free survival (PFS) was 63 days (95% CI, 43-105), and the median overall survival (OS) was 411 days (95% CI, 241-583).

In the phase 2 portion of the trial (n = 17), which evaluated annamycin at a dose of 330 mg/m², patients experienced improved disease control; the median PFS was 105 days, and the median OS was 13.5 months in an all-comer population with a median of 6 prior therapies.

Notably, patients from who had a response or SD after 2 cycles of annamycin achieved a median PFS of 112 and a median OS of 19.7 months.

Importantly, annamycin was not associated with any cardiotoxicity across all treatment cohorts, as confirmed by independent expert review.

“These positive topline results from MB-107 are incredibly encouraging. The impact annamycin demonstrated on median OS, particularly with patients who received multiple prior chemotherapy regimens, exceeded expectations. Additionally, the improvement seen with PFS after w doses represents a real potential for annamycin to provide a meaningful treatment option for the treatment of soft tissue sarcoma lung metastases,” Walter Klemp, chairman and chief executive officer of Moleculin, stated in a news release. “Looking ahead, we believe these results strongly support further evaluations of annamycin for the treatment of soft tissue sarcoma lung metastases, and we look forward to exploring opportunities to potentially bring this important treatment option to patients.”

MB-107 Trial Design

The multicenter, open-label, single-arm study enrolled patients at least 18 years of age with pathologically confirmed soft tissue sarcoma who had radiographically measurable disease in the lung; notably, those with extra-pulmonary disease were allowed to enroll.2 Patients needed to have lung metastases that were eligible for chemotherapy but not eligible for potentially curative surgical resection of pulmonary-only metastatic disease. Other key inclusion criteria comprised disease progression on prior therapy; a life expectancy of more than 3 months; an ECOG performance status of 2 or lower; an interval of at least 2 weeks from the last dose of prior treatment; and adequate hematologic and organ function.

In phase 2, annamycin was delivered via intravenous (IV) infusion over a 2-hour period on day 1 of each 21-day cycle.1 Treatment continued until radiographic evidence of disease progression per RECIST 1.1 criteria or the development of unacceptable toxicity

Patients returned to the study site every 21 days (±3 days) for comprehensive safety assessments. These assessments included adverse effect (AE) monitoring, physical examinations, vital signs, weight, electrocardiograms (ECGs), laboratory testing (complete blood count, clinical chemistry), and ECOG performance status evaluations.

Cardiac safety, a key focus of the study given annamycin's anthracycline backbone, was assessed with serial echocardiograms (ECHOs). ECHOs were conducted at baseline, following completion of the first 2 cycles, every other cycle thereafter, at the end of treatment (EOT) visit, and—when feasible—during follow-up at 6 months (±1 month) and 1 year (±1 month) post-treatment.

Tumor response evaluations were performed every 6 weeks (±1 week) during treatment starting from cycle 1, day 1, at the EOT visit, and every 3 months (±1 month) thereafter until disease progression. Subjects who discontinued therapy after achieving maximal response and did not receive subsequent anticancer therapy were followed for PFS every 3 months (±1 month). For patients who initiated additional treatment after discontinuation, only OS was followed, with post-treatment ECHOs at 6 and 12 months when feasible.

The incidence of dose-limiting toxicities was the trial’s primary end point.2 Secondary end points included efficacy outcomes and pharmacokinetics.

Annamycin previously received fast track and orphan drug designations from the FDA for relapsed/refractory acute myeloid leukemia, along with orphan drug designation for soft tissue sarcoma.1

References

1. Moleculin reports positive topline efficacy results from U.S. phase 1b/2 clinical trial evaluating annamycin for the treatment of soft tissue sarcoma lung metastases (MB-107). News Release. Moleculin Biotech. June 4, 2025. Accessed June 4, 2025. https://moleculin.com/moleculin-reports-positive-topline-efficacy-results-from-u-s-phase-1b-2-clinical-trial-evaluating-annamycin-for-the-treatment-of-soft-tissue-sarcoma-lung-metastases-mb-107/
2. Study of liposomal annamycin for the treatment of subjects with soft-tissue sarcomas (STS) with pulmonary metastases. ClinicalTrials.gov. Updated October 24, 2024. Accessed June 4, 2025. https://clinicaltrials.gov/study/NCT04887298