Winship researchers are testing for the first time in patients an investigational drug that is intended to improve outcomes for patients with relapsed myeloma, particularly for the 10% of those with multiple myeloma who face poor prognosis because they lack chromosome 17p.
The drug, Antibody Targeted Amanitin Conjugate HDP-101, was developed by the German company Heidelberg Pharma AG and is being studied in an open-label, multi-site Phase I/IIa clinical trial. The trial will evaluate the BCMA antibody-Amanitin conjugate for the treatment of relapsed or refractory multiple myeloma. The drug is being tested at three sites: Winship Cancer Institute of Emory University, the MD Anderson Cancer Center in Houston, and Heidelberg University hospital in Germany.
The trial's principal investigator at Winship, Jonathan L. Kaufman, MD, who is a professor in the Department of Hematology and Medical Oncology of Emory University School of Medicine and medical director of Winship's ambulatory infusion centers, treats patients with multiple myeloma and amyloidosis at Emory University Hospital. He says, "Based on the preclinical results, I have high hopes for this study with HDP-101. The payload Amantin is a novel agent in cancer therapy with a unique mode of action that differentiates it from other therapies and promises significant advantages for the treatment of myeloma."
The Amantin HDP-101 Trial
The trial's first part, a Phase I dose escalation study, will evaluate tolerability of different doses to determine either the maximum tolerated dose (MTD) or recommend a biologically active dose of HDP-101 for the Phase II part of the study. A planned 36 patients will receive HDP-101 intravenously every three weeks until disease progression, when it will be discontinued at the investigator’s discretion or the patient withdraws.
During Phase IIa, the recommended dose of HDP-101 will be administered to 30 patients. This phase will assess the drug's preliminary anti-tumor activity and further evaluate its safety. Patients in this phase will be stratified based on their 17p deletion status.
Preclinical data show that Amantin is potentially more effective against tumor cells that harbor the 17p deletion, which lets them bypass a cellular anti-tumor mechanism. Patients with the 17p deletion usually show shortened duration of benefit to established therapies and have a poor prognosis. The Phase IIa part of the trial is intended to evaluate both the efficacy of HDP-101 in multiple myeloma patients with or without a 17p deletion.
Multiple myeloma (MM) is uncommon but is the second most common type of bone and bone marrow cancer. Median age at diagnosis is 70 years, and patients can suffer from anemia, high calcium, kidney failure, bone pain and spontaneous fractures as well as other complications. Current treatment options include steroids, immunomodulatory drugs, proteasome inhibitors, immunotherapy and high dose chemotherapy supported by autologous stem cell transplantation.
"For many patients with multiple myeloma," says Kaufman, "currently available therapies stop working despite initial success, necessitating further treatment options. We are eagerly waiting for first clinical data for HDP-101, and hope to be able to expand the treatment options available to these patients."