The next-generation anthracycline analog annamycin demonstrated significant clinical activity in patients with soft tissue sarcoma lung metastases, achieving a 59.4% clinical benefit rate in the completed phase 1b/2 MB-107 trial. The multicenter, open-label study enrolled 36 evaluable patients and showed promising efficacy outcomes despite the heavily pretreated patient population.
Efficacy Results Exceed Expectations
In the study population evaluable for efficacy, the clinical benefit rate comprised 18 patients who achieved stable disease and 1 patient who experienced a partial response, with no complete responses observed. The median progression-free survival was 63 days (95% CI, 43-105), and the median overall survival reached 411 days (95% CI, 241-583) across all patients.
The phase 2 portion of the trial, which evaluated annamycin at the recommended dose of 330 mg/m², demonstrated particularly encouraging results. Despite patients having received a median of 6 prior therapies, the median progression-free survival was 105 days and median overall survival was 13.5 months in this all-comer population. These outcomes exceeded typical results for second-line monotherapies, which generally achieve overall survival of 8-12 months.
"The impact annamycin demonstrated on median overall survival, particularly with patients who received multiple prior chemotherapy regimens, exceeded expectations," stated Walter Klemp, chairman and chief executive officer of Moleculin. "Additionally, the improvement seen with PFS after two doses represents a real potential for annamycin to provide a meaningful treatment option for the treatment of soft tissue sarcoma lung metastases."
Enhanced Outcomes in Treatment Responders
Patients who achieved a response or stable disease after 2 cycles of annamycin showed substantially improved outcomes, with a median progression-free survival of 122 days and median overall survival of 19.7 months. This subset analysis demonstrated that achieving clinical benefit from annamycin resulted in meaningfully better long-term outcomes.
For patients with fewer prior therapies (≤2) receiving doses of annamycin ≤330 mg/m², overall survival reached 19.9 months with progression-free survival of 127 days, suggesting potential for even greater benefit in less heavily pretreated populations.
Safety Profile Addresses Key Concern
A critical finding from the MB-107 trial was the absence of cardiotoxicity across all treatment cohorts, as confirmed by independent expert review. This represents a significant advantage over traditional anthracyclines, which are associated with dose-limiting cardiac toxicity that restricts their clinical utility.
The study implemented comprehensive cardiac monitoring through serial echocardiograms conducted at baseline, following completion of the first 2 cycles, every other cycle thereafter, at end of treatment, and during follow-up at 6 months and 1 year post-treatment when feasible.
Trial Design and Patient Population
The MB-107 study enrolled patients at least 18 years of age with pathologically confirmed soft tissue sarcoma who had radiographically measurable disease in the lung. Patients needed to have lung metastases eligible for chemotherapy but not eligible for potentially curative surgical resection of pulmonary-only metastatic disease.
In phase 2, annamycin was administered as an intravenous infusion over 2 hours on day 1 of each 21-day cycle. Treatment continued until radiographic evidence of disease progression per RECIST 1.1 criteria or development of unacceptable toxicity. Tumor response evaluations were performed every 6 weeks during treatment.
Regulatory Status and Market Opportunity
Annamycin has 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. The drug also holds orphan drug designation from the European Medicines Agency for relapsed or refractory acute myeloid leukemia.
According to The American Cancer Society, approximately 13,500 individuals will be diagnosed with soft tissue sarcoma in 2025. The soft tissue sarcoma market was valued at $1.58 billion in 2024 and is expected to reach $2.57 billion by 2030, rising at a compound annual growth rate of 8.43%.
The positive results from MB-107 support further evaluation of annamycin for soft tissue sarcoma lung metastases, with Moleculin exploring opportunities to advance this treatment option toward potential regulatory approval and patient access.
