Proteolix, Inc. today announced positive clinical data demonstrating that the company's lead product, carfilzomib, has single-agent activity and promotes durable responses in patients with relapsed and refractory multiple myeloma.
Carfilzomib is the first in a new class of specific proteasome inhibitors being developed by Proteolix for the treatment of hematologic malignancies and solid tumors.
Sundar Jagannath, M.D., Chief of the Multiple Myeloma Program, Bone Marrow and Blood Stem Cell Transplantation at St. Vincent's Comprehensive Cancer Center in New York, and Ravi Vij, M.D., Associate Professor of Medicine, Division of Oncology, Section of Bone Marrow Transplantation at Washington University School of Medicine, presented data from two ongoing Phase 2 clinical trials of carfilzomib in relapsed and refractory multiple myeloma patients during the Novel Therapies for Myeloma and Related Disorders oral session at the 50th Annual Meeting of the American Society of Hematology (ASH). Both Phase 2 clinical trials are being conducted by Proteolix in collaboration with the Multiple Myeloma Research Consortium (MMRC).
Activity in Relapsed and Refractory Multiple Myeloma Patients
Dr. Jagannath presented data from an ongoing, open-label, multi-center study of single-agent carfilzomib in multiple myeloma patients. All patients in this trial were refractory to their last treatment. Of 39 evaluable patients, ten (26%) achieved partial or minor responses and an additional 16 (41%) achieved stable disease. Importantly, responses have also been durable with median treatment duration of 240 days, or approximately eight months.
"Patients enrolled in this Phase 2 trial have previously failed bortezomib, lenalidomide, thalidomide, and stem cell transplant. Carfilzomib as a single-agent is well tolerated and has demonstrated encouraging activity," said Dr. Jagannath.
The most common adverse events reported have been fatigue, anemia and thrombocytopenia. Patients with impaired renal function tolerated the drug and responses were independent of renal status. Treatment with carfilzomib was associated with a low incidence of peripheral neuropathy, a common side effect associated with the approved proteasome inhibitor, bortezomib. Exacerbation of pre-existing peripheral neuropathy was rare and did not result in dose reductions or discontinuation of therapy. Overall, carfilzomib was generally well tolerated and toxicities were manageable.
These data were presented by Dr. Jagannath in an oral presentation titled Initial Results of PX-171-003, an Open-Label, Single-Arm, Phase 2 Study of Carfilzomib in Patients with Relapsed and Refractory Multiple Myeloma (MM) (Abstract #864).
Carfilzomib Activity in Relapsed Patients by Prior Exposure to Bortezomib
A second presentation by Dr. Vij described interim results from a Phase 2 clinical trial of single-agent carfilzomib in multiple myeloma patients designed to evaluate response rates based on patients' bortezomib treatment history. Patients enrolled in this trial received one to three prior therapies, such as bortezomib, thalidomide, lenalidomide or stem cell transplantation and had subsequently relapsed. A total of 31 patients have been enrolled in this study and are currently evaluable for response.
Of fourteen evaluable bortezomib-naive patients, eight (57%) achieved responses, including one patient with a complete response, two with very good partial responses and five with partial responses. Four additional patients achieved stable disease. Among seventeen patients who have received prior treatment with bortezomib, three (18%) achieved partial responses, one patient achieved a minor response, and ten patients achieved stable disease. The median time to disease progression has not yet been established for this study.
According to Dr. Vij, "Single-agent carfilzomib has shown impressive and durable activity, notably among patients who have failed transplantation and have not yet received treatment with a proteasome inhibitor. The emerging safety profile makes this an attractive option in patients who have pre-existing neuropathy. Continued evaluation of carfilzomib in less heavily pre-treated patients is warranted given these promising findings."
Carfilzomib was generally well tolerated among relapsed patients and toxicities were manageable. The most common adverse events were fatigue, anemia and neutropenia. Two cases of tumor lysis syndrome were observed among bortezomib-naive patients, and with additional monitoring and management guidelines no further events have been reported. No treatment-emergent Grade 3 or 4 peripheral neuropathy was reported in this study.
Dr. Vij presented these interim data from a study of relapsed patients in a presentation titled Initial Results of PX-171-004, an Open-Label, Single-Arm, Phase 2 Study of Carfilzomib in Patients with Relapsed Multiple Myeloma (MM) (Abstract #865).
"We are encouraged by the data that show that carfilzomib is active and has been successful in providing durable responses in patients who have relapsed or who do not respond to currently available treatment options," said Lori A. Kunkel, M.D., Proteolix's Chief Medical Officer. "We believe carfilzomib may have broad application in the treatment of hematologic malignancies and solid tumors."
Supporting Preclinical Data