FDA Grants Rare Pediatric Disease Designation to Novel Radiopharmaceutical for Osteosarcoma

US FDA

The FDA has granted a rare pediatric disease designation to the bone-targeting radiopharmaceutical, Samarium-153-DOTMP (CycloSam), for use as a potential therapeutic option for patients with osteosarcoma.¹

The nuclear technology utilizes low specific activity Samarium-153, which reduces europium impurity, and DOTMP, which is a chelator that is thought to eliminate off-target migration and to target sites of high bone turnover. The product also utilizes a streamlined manufacturing process that is already in place.

The product also delivers targeted radiation selectively to the skeletal system, and as such, it is hypothesized to be favorable to leverage in bone marrow ablation as preconditioning for bone marrow transplantation, and in procedures to reduce external beam radiation to bone tumors.

“Combined with the orphan drug designation for osteosarcoma that we received last year from the FDA, the rare pediatric disease designation may allow QSAM Biosciences Inc. to potentially bring CycloSam to market more rapidly through additional incentives and eligibilities that ultimately help these young patients for whom there is currently little hope,” Douglas Baum, chief executive officer at QSAM, stated in a press release.

A dose-finding phase 1 trial (NCT03612466) has been launched to evaluate the radiopharmaceutical product both alone and in combination with external beam radiotherapy.² To be eligible for participation, patients need to have a histologically confirmed diagnosis of a solid tumor metastatic to bone, or a histologically confirmed diagnosis of osteosarcoma with either an unresectable primary tumor or metastases.

Patients also need to have measurable disease, acceptable renal and hematologic function, a life expectancy of at least 8 weeks, a Karnofsky performance status greater than 50%, and they must have previously received effective therapy for their underlying disease and have no potentially curative options available to them.

If patients previously received radiotherapy to all known areas of their current disease, have a known contraindication to radiotherapy, or are pregnant or breastfeeding, they will be excluded.

The study design comprises a total of 6 cohorts, and the first 3 cohorts will evaluate the product by itself. If determined to be safe, subsequent cohorts will then receive the product followed by external beam radiotherapy.

Patients will have a peripheral blood stem cell harvest in anticipation of prolonged myelosuppression. They will receive 2 doses of the radiopharmaceutical agent, which will be administered 7 days apart. Stem cells will be reinfused 24 days after the initial dose received, if needed.

Dose levels 1 through 3 will comprise treatment with the radiopharmaceutical alone, and if the maximum tolerated dose (MTD) has not been reached at level 3, then external beam radiotherapy will be added to dose levels 4 through 6, beginning on day 15.

Those enrolled to the cohorts receiving dose levels 4 through 6 will receive external beam radiotherapy to all radiographically evident sites of disease. If the MTD is not determined at level 6, then the study will end, and dose level 6 will be established as the recommended phase 2 dose of the product.

Participants will undergo disease re-evaluation 30 days after they complete all study treatment. They will also be assessed at 4, 6, 8, and 12 months thereafter, unless they experience progressive disease.

The primary outcome measure for the trial is to identify the MTD. Key secondary outcome measures include overall survival, time to progression, and clinical response rate at 30 days, 4 months, 8 months, and 12 months, after treatment completion.

“Patients with this disease are eligible to participate in our current phase 1 clinical trial, however, we anticipate that we will initiate a separate clinical trial in the coming year specifically focused on primary bone cancers, such as osteosarcoma and Ewing sarcoma,” Baum added in the press release. “We are dedicated as a company to making a difference in the lives of children and their families battling these forms of bone cancer.”

In August 2021, the FDA granted an orphan drug designation to CycloSam for use as a potential option in patients with osteosarcoma.³

References

1. QSAM Biosciences receives rare pediatric disease designation from FDA for CycloSam in the treatment of osteosarcoma. News release. QSAM Biosciences, Inc.; February 2, 2022. Accessed February 2, 2022. https://yhoo.it/3gktiqE
2. A dose finding study of CycloSam® combined with external beam radiotherapy. ClinicalTrials.gov. Updated December 6, 2021. Accessed February 2, 2022. https://clinicaltrials.gov/ct2/show/NCT03612466
3. QSAM Biosciences receives orphan drug designation from FDA for CycloSam in the treatment of osteosarcoma. News release. QSAM Biosciences, Inc.; August 18, 2021. Accessed February 2, 2022. https://bit.ly/3J0ZprA