Tuesday, April 21, 2015
Two encouraging Memorial Sloan Kettering Cancer Center (MSK) studies were featured in this year’s American Association for Cancer Research (AACR) Annual Meeting press program. The AACR is the world’s oldest and largest professional organization dedicated to advancing cancer research and the press program highlights cancer research that a panel of AACR experts considers the most significant of the year and deserving of media attention.
Richard O’Reilly, Chair of the Department of Pediatrics and Chief of the Pediatric Bone Marrow Transplant Service and Susan Prockop, Assistant Attending in the Pediatric Bone Marrow Transplantation Service shared promising news from two clinical trials, testing a treatment for Epstein-Barr virus–associated lymphoproliferative disorder (EBV-LPD). More than 60 percent of patients with EBV-LPD who were not responding to standard rituximab (Rituxan) treatment did respond to a new type of immunotherapy called Epstein-Barr virus– specific cytotoxic T lymphocyte (EBV-CTL) therapy.
This new method involved giving patients cytotoxic T cells (CTLs) from a donor with normal immune function. The trial results showed that EBV-CTL therapy is effective, putting more than 60 percent of patients into long-lasting remission whether the T cells are collected from the patient’s transplant donor or from a bank of T cells contributed by healthy third-party donors. MSK has created a bank of more than 300 types of modified EBV immune T cells that are ready for use almost immediately. Side effects in both trials were minimal and without serious complications.
Out of the 39 trial participants in the first clinical trial, 26 patients received three weekly doses of T cells generated from their transplant donor, and 13 received HLA-matched, EBV-CTLs generated from MSK’s bank of EBV-CTLs generated from third-party healthy donors. Of those, 23 trial participants responded completely, with nine having already survived five or more years since treatment.
In the second trial, only EVB-CTLs from the bank at MSK were used. Among the 18 trial participants, nine had a complete response; three had partial responses that have been durable; and one had stable disease. All of those who achieved a complete response continue to do well, and researchers will be following the patients long-term.
“The good news from our two clinical trials is that EBV-CTLs generated from either the patient’s transplant donor or from the bank of normal donor T cells developed at Memorial Sloan Kettering put aggressive EBV-LPD that had failed to respond to rituximab into long-lasting remission in more than 60 percent of patients.” said Dr. O’Reilly.
Based on this success, the U.S. Food & Drug Administration (FDA) granted MSK Breakthrough Therapy Designation to develop EBV-CTLs from third parties. MSK is working with Atara Biotherapeutics, Inc. to continue refining and expanding the technology.
Medical oncologist Maura Dickler reported encouraging results from a first-in-human phase I/IIa clinical trial that suggests a new drug for breast cancer is safe, enabling research to move forward into the next phase testing its effectiveness.
Dr. Dickler reported that the new investigational estrogen receptor degrader GDC-0810 was safe and tolerable in postmenopausal women with advanced breast cancer positive for the estrogen receptor (ER), and a subset of the women — all of whom were previously treated with standard endocrine therapy — gained clinical benefit from the drug. The drug could help patients who have become resistant to current therapies or whose breast cancer has returned.
The clinical trial tested GDC-0810 in women with ER-positive breast cancer that has returned or continued growing after standard hormonal therapy. PET imaging using a fluorescent agent revealed that the drug occupies the ER receptors efficiently and prevents estrogen from being taken up by the cancer cells.
“Resistance to hormone therapy is a major problem for women with metastatic, ER-positive breast cancers, and new treatments are urgently needed.” explained Dr. Dickler.
The findings suggest the drug might be effective against tumors that have developed resistance to standard hormone therapy due to mutated ER receptors. Side effects of the drug were manageable. “Therapies such as GDC-0810 that are effective against these treatment-resistant tumors could be a significant advance for these patients,” Dr. Dickler added.