Camsirubicin Reduces Tumor Size in Advanced Soft Tissue Sarcoma

Treatment with camsirubicin (MNPR-201; GPX-150; 5-imino-13-deoxydoxorubicin) led to a reduction in tumor size in patients with advanced soft tissue sarcoma, according to data from an ongoing phase 1b trial (NCT05043649).¹

Findings showed that 2 patients treated at 650 mg/m2 of camsirubicin experienced tumor size reductions of 18% and 20%, respectively, following the first 2 cycles of treatment. Additional cycles of therapy are planned for both patients.

At the previously investigated dose level of 520 mg/m2, 1 patient achieved a 21% reduction in tumor size after 6 cycles of treatment. After having unresectable disease at the time of enrollment, this patient underwent successful surgery with clear margins. Additionally, all 3 patients in the 520 mg/m2 cohort experienced stable disease with either a net reduction or no change in tumor size per RECIST v1.1 criteria.

Although doxorubicin is the standard frontline treatment for patients with advanced soft tissue sarcoma, patients discontinue treatment after 6 to 8 cycles because of the risk of irreversible heart damage.

Camsirubicin is a novel proprietary analog of doxorubicin that is designed to retain the anticancer activity of doxorubicin and minimize the toxic effects on the heart.²

The open-label, single-arm, dose-escalation, phase 1b trial is enrolling patients at least 18 years of age with locally confirmed histological diagnosis of advanced unresectable or metastatic malignant soft tissue sarcoma that is not amenable to curative treatment with surgery or radiotherapy.3 Patients are also required to have measurable disease per RECIST v1.1 criteria, an ECOG performance status of 0 or 1, and a left ventricular ejection fraction (LVEF) of at least 50% within 28 days of enrollment.

Patients are not allowed to have received prior treatment with anthracyclines in any setting or any prior systemic cytotoxic therapies for advanced or metastatic sarcoma. Other key exclusion criteria include known active central nervous system or leptomeningeal metastasis, or prior radiotherapy of the mediastinal/pericardial area or whole pelvis radiation.

The study began with camsirubicin administered at 265 mg/m2 once every 3 weeks for 6 cycles. Doses are being increased in increments of 50% until a grade 2 non-hematologic toxicity is observed. After this occurrence, doses will be escalated by 25% until a maximum tolerated dose (MTD) is established. All patients are also receiving 6 mg of prophylactic pegfilgrastim approximately 24 to 96 hours following each camsirubicin infusion to prevent neutropenia.

The primary end points of the study are to establish the MTD and the recommended phase 2 dose. The incidence of treatment-emergent adverse effects is a secondary end point.

Regarding safety, drug-related cardiotoxicity defined by the industry standard LVEF has not been observed. Additionally, dose cohorts have not needed to be expanded because of toxicities. Seventy-one percent of patients treated with camsirubicin did not experience hair loss, and 14% experienced hair loss of more than 50%. Furthermore, mild-to-severe oral mucositis was reported in 14% of patients.

References

1. Monopar provides encouraging camsirubicin clinical data update. News release. Monopar Therapeutics. August 8, 2023. Accessed August 8, 2023. https://ir.monopartx.com/press-releases/detail/75/monoparprovides-encouraging-camsirubicin-clinical-data
2. Camsirubicin. Monopar Therapeutics. Accessed August 8, 2023. https://www.monopartx.com/pipeline/Camsirubicin
3. Camsirubicin + pegfilgrastim to determine MTD in ASTS. ClinicalTrials.gov. Updated May 30, 2023. Accessed August 8, 2023. https://classic.clinicaltrials.gov/ct2/show/NCT05043649