Early-Phase Annamycin Clinical Trial for STS Lung Metastases Achieves Enrollment Goal

Sant P. Chawla, MD

The target number of patients with soft tissue sarcoma (STS) lung metastases have been enrolled in the phase 1b/2 study of annamycin, commencing the recruiting portion of the trial, announced Moleculin Biotech, in a press release.¹

The clinical trial milestone followed a fast track designation granted by the FDA to annamycin for the treatment of this patient population. The agent also received an orphan drug designation. Interim results from the study are expected to be reported in the second quarter of 2022, according to the company.^1,2

"With limitations in the current treatment landscape for STS, there remains a significant unmet need for patients and physicians. We are pleased to see the progress of this important study to evaluate Annamycin, which has demonstrated a lack of cardiotoxicity in recent human clinical trials, one of which is ongoing. I continue to be encouraged by the data seen to date and look forward to the continued advancements of this study toward offering potential hope to patients battling this difficult to treat cancer," added Sant P. Chawla MD, Director, Sarcoma Oncology Center, Director, Cancer Center of Southern California, in the press release.¹

The study will follow a multicenter, open-label, single-arm design with the goal of determining the maximum-tolerated dose (MTD) or the recommended phase 2 dose (RP2D) and safety of Annamycin in the first phase. In the phase 2 portion of the study, the primary end point is the efficacy of annamycin in patients with STS lung metastases. The maximum number of patients enrolled in phase 2 is 25.

Preclinically, annamycin demonstrated high in vivo activity in lung metastatic cancer models.3 The agent had a high cytotoxic potency and could overcome ATP-binding cassette transporter-mediated efflux and achieve a high intracellular uptake compared with a similar agent, doxorubicin. Further, annamycin showed a concentration in the lungs that was 6 times greater than that observed with doxorubicin, underscoring in vivo efficacy in lung-localized tumor models. The outcome of the analysis overall was that annamycin had a significantly higher uptake in the lungs when compared with doxorubicin.²

Subjects in the sarcoma lung metastasis model had a median survival of 87.5 days with annamycin versus only 21 days with saline. The survival ratio observed was 4.17 with annamycin versus 1 with saline (P < .0001).

Annamycin is a next-generation anthracycline agent. Annamycin has been shown to accumulate in the lungs at up to 30-fold the level of the current standard-of-care treatment, doxorubicin.

"We are pleased to have commenced patient enrollment and dosing in this important program evaluating annamycin, which we believe has the potential to address the limitations with current treatment options for STS lung metastases. Our team is committed to driving continued progress for the development of Annamycin. We look forward to getting the trial well-underway toward interim data and potentially address the unmet medical needs in the treatment of these highly resistant tumors," commented Walter Klemp, chairman, and chief executive officer of Moleculin, in a statement.¹

_References:

_{1. Moleculin announces first subject enrolled and dosed in phase 1b/2 clinical trial of annamycin for the treatment of sarcoma lung metastases. News release. Moleculin Biotech. June 21, 2021. Accessed June 25, 2021.}

_{2. Moleculin receives FDA approval of fast track designation for annamycin in the treatment of sarcoma lung metastases. News release. Moleculin Biotech, Inc. March 30, 2021. Accessed June 25, 2021. https://prn.to/39wCAwJ}

_{3. Zielinski R, Grela K, Zuniga RC, et al. Targeting sanctuary sites of cancer: Novel approaches to treatment of lung localized tumors. Poster presented at: 2020 AACR Annual Meeting; June 22-24, 2020; Virtual. Abstract 3074.}