Annamycin Showcases Early Clinical Activity in Soft Tissue Sarcoma Lung Metastases

Pipeline Report | <b>Pipeline Report: October 2021</b>

Treatment with the next-generation anthracycline annamycin was found to result in preliminary clinical activity without dose-limiting toxicities in patients with soft tissue sarcoma lung metastases.

Treatment with the next-generation anthracycline annamycin was found to result in preliminary clinical activity without dose-limiting toxicities (DLTs) in patients with soft tissue sarcoma lung metastases, according to early data from 2 cohorts of an ongoing phase 1/2 trial (NCT04887298).1

In the first cohort, 1 patient is still receiving annamycin and is currently in cycle 5 of treatment. The patient is anticipated to enter cycle 6 at the end of October. At the end of cycle 4, a scan demonstrated that the patient had stable disease. Another subject discontinued the agent after 6 cycles of treatment, which translated to 4.5 months. This patient stopped treatment because of disease progression, although disease stability was maintained up to that time point. A third patient discontinued annamycin following cycle 1. Following the end-of-study scan, stable disease was observed. The patient discontinued the study because cycle 2 treatment was delayed for more than 6 weeks from the previous dosing.

In the second cohort, 1 patient is still receiving annamycin and is currently in cycle 3 of treatment. At the end of cycle 2, a scan indicated that the patient achieved a partial response defined as more than a 30% reduction in tumor size. Another patient discontinued the study following 2 cycles of treatment and an end-of-cycle scan that showed progressive disease. Another patient received 1 cycle of treatment and discontinued due to reasons unrelated to the study treatment. Results from the end-of-study scan for this patient are pending.

“To witness the activity of annamycin in the treatment of soft tissue sarcoma lung metastases, even this early in a phase 1 trial, we believe is encouraging,” Walter Klemp, chairman and chief executive officer of Moleculin Biotech, Inc., stated in a press release. “Four of the 5 patients who have completed scans to date demonstrated a response to treatment, including 3 with extended and, in 1 case, continuing stable disease and 1 patient with a substantial reduction in tumor size. These interim data bolster our optimism about the potential for annamycin to address the limitations with the current standard-of-care treatment options for soft tissue sarcoma lung metastases.”

To be eligible for enrollment on the phase 1 trial, patients needed to have a pathologically confirmed diagnosis of soft tissue sarcoma and documented lung metastases; they needed to be candidates for chemotherapy, but not eligible for potentially curative surgical resection of pulmonary-only metastatic disease.2

Moreover, patients needed to be at least 18 years of age, have previously received anthracycline therapy for their disease and experienced disease progression before study entry, have measurable disease, an estimated life expectancy of longer than 3 months, an ECOG performance status of 0 to 2, and acceptable laboratory results.

If they had a condition that puts them at unacceptable risk; left ventricular ejection fraction of less than 50%, valvular heart disease, or severe hypertension; a baseline QT/QTc interval of longer than 480 milliseconds, or clinically relevant serious comorbid medical conditions, they were excluded.

Study participants received annamycin via a 2-hour intravenous infusion on day 1, followed by 20 days off; cycle 1 of treatment consisted of 21 days. Patients visit the study site every 21 days, plus or minus 3 days, so that they can be monitored for safety, given a physical examination, undergo laboratory evaluations, get their vital signs checked, have their weight measured, get their ECOG performance status tested, and to get electrocardiograms performed. This is all followed by an infusion of the study drug.

Additional laboratory assessments like clinical chemistry and complete blood count, will be done at 7 days, plus or minus 3 days, and 14 days, plus or minus 3 days, from infusion with annamycin for further safety monitoring each cycle. Cardiac function evaluation will be followed by echocardiograms at the time of screening, at the end of the first 2 cycles, and then every other cycle thereafter. They will be done at the end of the treatment visit and during follow-up, if possible, at 6 months, plus or minus 1 month, and 1 year, plus or minus 1 month, following treatment discontinuation.

Patients will continue to receive treatment with annamycin every 21 days until disease progression or intolerable toxicity.

Moreover, investigators are examining tumor response every 6 weeks, plus or minus 1 week, from the first day of the first cycle of treatment and at the end-of-treatment visit; this will then be done every 3 months, plus or minus 1 month, until progressive disease.

Patients who discontinue the study after having experienced a maximum response and who do not begin another treatment will be followed every 3 months, plus or minus 1 month, to observe progression-free survival. Those who go on to another treatment following study discontinuation will only be followed for overall survival.

Moleculin Biotech, Inc. has opened enrollment for the third cohort of the phase 1b portion of the research. At minimum, 3 patients will be enrolled to each dosing cohort until a maximum tolerated dose of annamycin is determined. The maximum number of patients per cohort is 6, so up to 36 patients may be enrolled to this phase of the trial.

“Ultimately, we believe annamycin has the potential to bring a new and effective treatment option to patients with a significant unmet need,” Klemp added. “With these data now in hand, we are cautiously optimistic as we begin patient enrollment and dosing in the next cohort.”

In March 2021, the FDA granted a fast track designation to annamycin as treatment for patients with soft tissue sarcoma lung metastases.3 The designation followed preclinical data reported at the 2020 AACR Annual Meeting, as well as from an independent laboratory, which

demonstrated that the agent was able to reach 6- to 34-fold higher levels of accumulation in the lungs compared with doxorubicin.4

In December 2020, the FDA granted an orphan drug designation to annamycin for the treatment of patients with soft tissue sarcomas.5

References

  1. Moleculin announces interim data in phase 1b/2 clinical trial of annamycin for the treatment of soft tissue sarcoma lung metastases. News release. Moleculin Biotech, Inc. October 18, 2021. Accessed October 26, 2021. https://bit.ly/318sDo9
  2. Study of liposomal annamycin for the treatment of subjects with soft-tissue sarcomas (STS) with pulmonary metastases. ClinicalTrials.gov. Updated September 22, 2021. Accessed October 26, 2021. https://clinicaltrials.gov/ct2/show/NCT04887298
  3. Moleculin receives FDA approval of fast track designation for annamycin in the treatment of sarcoma lung metastases. Moleculin Biotech, Inc. October 26, 2021. Accessed March 30, 2021. https://prn.to/3rzZZ6H
  4. Moleculin announces Annamycin receives FDA orphan drug designation for soft tissue sarcomas. Moleculin. News release. December 29, 2020. Accessed October 26, 2021. https://prn.to/2L3KioK
  5. Moleculin announces Annamycin receives FDA orphan drug designation for soft tissue sarcomas. Moleculin. News release. December 29, 2020. Accessed October 26, 2021. https://prn.to/2L3KioK