Camsirubicin Elicits Early Clinical Activity in Advanced Soft Tissue Sarcoma

The doxorubicin analogue camsirubicin in combination with pegfilgrastim (Neulasta) produced encouraging clinical activity and safety in patients with advanced soft tissue sarcoma, according to data from a phase 1b trial (NCT05043649).¹

Findings showed that among 10 evaluable patients, 5 achieved stable disease at 12 weeks. The remaining 5 patients experienced progressive disease. Notably, an 11th patient met the criteria for stable disease at 6 weeks but died due to COVID-19 prior to the week 12 evaluation.

Doxorubicin is approved by the FDA as first-line monotherapy for the treatment of patients with advanced soft tissue sarcoma. However, due to its risk of irreversible, life-threatening cardiotoxicity, treatment with doxorubicin is stopped once a lifetime cumulative dose is reached in approximately 4 to 6 months.²

Camsirubicin was designed via chemical modification to mitigate cardiotoxicity while retaining antitumor activity. Data from a previous phase 1 dose-escalating trial suggested a recommended phase 2 dose (RP2D) of 265 mg/m2 due to concerns of acute neutropenia. The phase 1b trial added pegfilgrastim with camsirubicin to address neutropenia toxicity to determine a higher maximum tolerated dose (MTD) for future studies.

The ongoing phase 1b trial is enrolling patients at least 18 years of age with a locally confirmed histological diagnosis of advanced unresectable or metastatic soft tissue sarcoma including leiomyosarcoma, dedifferentiated liposarcoma, myxoid liposarcoma, pleomorphic liposarcoma, undifferentiated pleomorphic sarcoma, malignant peripheral nerve sheath tumor, or synovial sarcoma who were not amenable to curative treatment with surgery or radiotherapy.³

Other key inclusion criteria include measurable disease, an ECOG performance status of 0 or 1, no previous treatment with anthracyclines, and no prior systemic cytotoxic therapies for advanced/metastatic sarcoma, left ventricular ejection fraction of at least 50% assessed within 28 days prior to enrollment, and adequate hepatic, renal, cardiac, and hematologic function.

All previous anticancer treatments must be completed at least 21 days prior to first dose of study drug.

Key exclusion criteria include intolerance to pegfilgrastim, known active central nervous system or leptomeningeal metastasis, prior treatment with doxorubicin, epirubicin, idarubicin, and/or other anthracyclines or anthracenediones, or prior radiotherapy of the mediastinal/pericardial area or whole pelvis radiation.

In the 3+3 trial design, patients received pegfilgrastim plus escalating doses of camsirubicin, starting at 265 mg/m2 (n = 3). Other doses of camsirubicin included 330 mg/m² (n = 3), 410 mg/m² (n = 3), and 520 mg/m² (n = 2). The trial has advanced to the fourth cohort without any dose-limiting toxicity. Treatment with camsirubicin consists of 6, 21-day cycles, with an extension of up to 16 cycles.

The co-primary end points of the trial are to determine the MTD and RP2D.

Among the 11 enrolled patients, the median age was 49 years (range, 26-81). Eight patients were male, and all 11 had an ECOG performance status of 1. One patient had a localized tumor, 5 patients had locally advanced disease, and 5 patients had metastatic disease.

No drug-related cardiotoxicity was observed up to current dose level of 520 mg/m² per cycle.

References

1. Monopar announces encouraging clinical data from ongoing camsirubicin phase 1b trial. News release. Monopar Therapeutics Inc. November 16, 2022. Accessed November 18, 2022. http://bit.ly/3EG2JJA
2. Chua VS, Chawla S, Gordon E. Phase 1b trial of camsirubicin, a novel doxorubicin analog, with concomitant pegfilgrastim for advanced soft tissue sarcoma to identify a new maximum tolerated dose/recommended phase 2 dose. Presented at: 2022 Connective Tissue Oncology Society (CTOS) Annual Meeting; November 16-19, 2022; Vancouver, BC, Canada. http://bit.ly/3tIgpgS
3. Camsirubicin + pegfilgrastim to determine MTD in ASTS. ClinicalTrials.gov. Updated September 20, 2021. Accessed November 18, 2022. https://clinicaltrials.gov/ct2/show/NCT05043649