Camsirubicin Elicits Encouraging Safety/Efficacy Data in Advanced Soft Tissue Sarcoma

The ongoing phase 1b clinical trial (NCT05043649) evaluating camsirubicin in patients with advanced soft tissue sarcoma revealed 50% of patients to have stable disease (SD) with no drug-related clinical cardiotoxicity observed in any patient.

Currently, the trial is at its 4th dose level of 520 mg/m2, almost 2 times the starting dose of the trial. As the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) has not been reached, the trial continues to enroll patients and escalate the dose.

Doxorubicin is the current first-line standard of care treatment for most patients with advanced soft tissue sarcoma. However, previous exploratory studies of camsirubicin patients with cancer demonstrated the potential to treat patients at higher dose levels for over a year. In these preclinical and exploratory clinical studies, no irreversible heart toxicity with camsirubicin was observed in any patients.

This current phase 1b study aims to evaluate whether camsirubicin can be given at an even higher dose than what was previously achieved with doxorubicin. In the open-label, dose-escalation study, investigators look to determine the MTD of camsirubicin plus pegfilgrastim in patients with advanced soft tissue sarcoma.

After a screening period of up to 28 days, patients enrolled will receive camsirubicin through intravenous infusion at an 8 mg/min rate on day 1 of a 21-day cycle for 6 cycles. If patients demonstrate clinical benefit when they complete 6 cycles, they are allowed to continue to receive camsirubicin until disease progression, unacceptable toxicity, or completion of their 16th cycle.

For the first 3 patients enrolled in the trial, the starting dose was set at 265 mg/m2. With a positive recommendation from the trial safety review committee at the completion of each dose level, the trial is allowed to then treat at least three new patients at the next dose level, which is 25% higher.

Primary end point of the study is to establish the MTD/RP2D of camsirubicin with pegfilgrastim (Neulasta). Other end points include assessing the safety profile, efficacy, progression-free survival, time to progression, overall response rate, duration of response, overall survival, and pharmacokinetics.

Eleven patients, including 8 females and 3 males, have been enrolled in the trial. The median age of those enrolled is 49 years (range, 26-81) and all had an ECOG performance status of 1. At baseline, tumors were advanced and metastatic in 5 patients each and localized in 1 patient.

Findings revealed that 5 of 10 patients exhibited SD at 12 weeks and 1 patient who met the criteria for SD at the first CT scan at 6 weeks died due to COVID-19 and was not evaluable at the 12-week CT scan. There also were no drug-related clinical cardiac toxicities seen in any patient. This was tracked by left ventricular ejection fraction which is an industry standard measure of cardiotoxicity.

Overall, these findings show that this subtype of patients who achieved SD when treated with camsirubicin is in line with those who are more likely to respond to doxorubicin.

_REFERENCES:

_{1. Monopar announces encouraging clinical data from ongoing camsirubicin phase 1b trial. News release. Monopar Therapeutics Inc. November 16, 2022. Accessed November 17, 2022. https://yhoo.it/3gbpbkg}

_{2. Chua VS, Chawla S, Gordon E, et al. 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: Connective Tissue Oncology Society (CTOS) Annual Meeting; November 16-19, 2022; Vancouver, Canada.}