SAN DIEGO, CA - A combination of two targeted agents - one approved by the Food and Drug Administration and one undergoing testing - has demonstrated safety as well as encouraging signs of effectiveness in a phase 1 clinical trial in patients with relapsed or hard-to-treat chronic lymphocytic leukemia (CLL) or mantle cell lymphoma (MCL). Dana-Farber Cancer Institute researchers will report the findings at the 58th annual meeting of the American Society of Hematology (ASH).
The combination of the approved drug ibrutinib and the novel agent TGR-1202 is being tested in patients to determine if the two agents can be safely given at the same time and whether they lead to more durable remissions in CLL and MCL compared to ibrutinib alone. While ibrutinib, which targets the cell protein BTK, often reduces the amount of cancer in patients with relapsed or drug-resistant CLL or MCL, it rarely eliminates the cancer or generates long-lasting results in MCL or high-risk forms of CLL. By pairing it with TGR-1202, which blocks the P13K-delta protein, researchers hope to disable two key parts of cancer cells' growth circuitry.
As of late July, investigators had treated 28 patients - 17 with CLL, 11 with MCL - with the tandem therapy. The regimen was shown to be safe, with an 800 mg dose of TGR-1202 found to be suitable for further study.
"The efficacy of the combination looks promising as well," said Dana-Farber's Matthew Davids, MD, principal investigator of the investigator-initiated trial. Davids will present the findings Monday, December 5, at 8 a.m. in Room 5AB of the San Diego Convention Center. "We have already seen a complete response - no evidence of cancer - in one patient with CLL, and several other patients are approaching complete response," Davids added.
Another potential benefit of the two-drug combination is that it could offer greater flexibility in treatment, Davids remarked. Patients who need to discontinue one of the drugs because of temporary complications could continue with the other and resume the two-drug regimen when the complications subside.
While enrollment of patients with CLL in the trial is complete, openings remain for patients with MCL, and the study is open at several sites across the country through the Blood Cancer Research Partnership, a Dana-Farber-led hematologic malignancies research consortium funded through the Leukemia & Lymphoma Society.
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The senior author of the study is Jennifer Brown, MD, PhD, of Dana-Farber. Co-authors are Haesook Kim, PhD, Alyssa Nicotra, Alexandra Savell, Karen Francoeur, RN, Jeffrey Hellman, PA-C, Caron Jacobson, MD, and David C. Fisher, MD, of Dana-Farber; Hari Miskin, MS, and Peter Sportelli of TG Therapeutics, New York, N.Y.; Asad Bashey, MD, PhD, of Northside Hospital, Atlanta, Ga.; Laura Stampleman, MD, of Pacific Cancer Care, Monterey, Cal.; Jens Rueter, MD, of Eastern Maine Medical Center; Adam Boruchov, MD, of Saint Francis Hospital and Medical Center, Hartford, Conn.; and Jon Arnason, MD, of Beth Israel Deaconess Medical Center.
Research funding for the study was provided by TG Therapeutics (New York, NY).
About Dana-Farber Cancer Institute
From achieving the first remissions in childhood cancer with chemotherapy in 1948, to developing the very latest new therapies, Dana-Farber Cancer Institute is one of the world's leading centers of cancer research and treatment. It is the only center ranked in the top 4 of U.S. News and World Report's Best Hospitals for both adult and pediatric cancer care.
Dana-Farber sits at the center of a wide range of collaborative efforts to reduce the burden of cancer through scientific inquiry, clinical care, education, community engagement, and advocacy. Dana-Farber/Brigham and Women's Cancer Center provides the latest in cancer care for adults; Dana-Farber/Boston Children's Cancer and Blood Disorders Center for children. The Dana-Farber/Harvard Cancer Center unites the cancer research efforts of five Harvard academic medical centers and two graduate schools, while Dana-Farber Community Cancer Care provides high quality cancer treatment in communities outside Boston's Longwood Medical Area.
Dana-Farber is dedicated to a unique, 50/50 balance between cancer research and care, and much of the Institute's work is dedicated to translating the results of its discovery into new treatments for patients locally and around the world.