CAMBRIDGE, Mass.—With an eye toward treatment of hematological malignancies, Dragonfly Therapeutics Inc. announced June 12 a global strategic collaboration with Celgene Corp. and its affiliates to discover, develop and commercialize innovative immuno-oncology treatment options based on Dragonfly’s natural killer (NK) cell-based TriNKET technology platform.
“NK cell biology and immunotherapy are increasingly critical areas of hematologic research and we are looking forward to working with Dragonfly’s team of world-leading experts,” said Dr. Rupert Vessey, president of research and early development for Celgene. “This collaboration will leverage the strengths of each company as we work together to bring innovative therapies to patients.”
“Through execution of this strategic alliance with Celgene, Dragonfly is well positioned to accelerate our efforts to bring potential new immuno-oncology treatment options to patients with hematological malignancies,” added Bill Haney, co-founder and CEO of Dragonfly. “Celgene is a preeminent biopharmaceutical company with a demonstrated history of recognizing disruptive science that may lead to new treatment options for patients with cancer. We look forward to a successful collaboration.”
Under the terms of the deal, which includes a $33-million upfront payment and potential future milestone and royalty payments, Celgene gains an exclusive option to in-license worldwide rights for as many as four therapeutic candidates with potential utility in the treatment of acute myeloid leukemia (AML), multiple myeloma and additional hematological malignancies.
In the span of a couple days roughly a week before this announcement, Celgene put out two news releases on clinical progress in AML and multiple myeloma.
The first was news that bluebird bio Inc. and Celgene was sharing updated results at the American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago from the ongoing CRB-401 Phase 1 clinical study of bb2121—an investigational anti-BCMA CAR T cell therapy—in 18 patients with relapsed/refractory multiple myeloma. The objective of this Phase 1 dose-escalation study is to evaluate safety and efficacy of bb2121 and determine a recommended Phase 2 dose for the drug, which bluebird bio and Celgene are jointly developing.
“It is impressive to see objective responses in all patients treated at dose levels of 150x106 CAR+ T cells or higher in such a heavily pretreated population, including those with high tumor burden. We are encouraged by the duration and depth of responses, and pleased that the safety profile remains readily manageable,” said Dr. David Davidson, chief medical officer at bluebird bio. “Although these data are still early, it is encouraging that no patient in the active dose cohorts has had myeloma progression. In light of these results, we look forward to initiating the expansion phase of the CRB-401 study in the coming months.”
“The heavily pretreated, relapsed/refractory patients in this study have few effective treatment options, highlighting the importance of this interim data. All patients previously underwent autologous HSCT, and received a median of seven lines of prior therapy,” commented Michael Pehl, president of hematology and oncology for Celgene. “The consistency, depth and durability of these patients’ responses coupled with a manageable safety profile is very exciting, and we believe will provide hope for patients in this setting. Efforts are underway to advance the development of bb2121 for patients with relapsed/refractory multiple myeloma.”
The other news was that Celgene and Agios Pharmaceuticals Inc. had announced new efficacy and safety data from the ongoing Phase 1 dose-escalation and expansion study evaluating investigational oral Idhifa (enasidenib) in patients with relapsed or refractory AML (R/R AML) and an isocitrate dehydrogenase-2 (IDH2) mutation. Idhifa is an investigational first-in-class, oral, targeted inhibitor of the mutant IDH2 enzyme, which demonstrated an overall response rate of 40.3 percent, including a complete response rate of 19.3 percent in the study. These data were also presented at the ASCO meeting.
“The updated results, including duration of response, from the Phase 1 study reinforce the potential for enasidenib as a first-in-class therapy for patients with relapsed or refractory AML and an IDH2 mutation,” said Pehl. “Patients have very few treatment options for relapsed or refractory AML, so we are eager to advance this potential targeted therapy as quickly as possible.”
As of April 15, 2016, a total of 239 patients with advanced hematologic malignances and an IDH2 mutation were enrolled into the Phase 1 study, of which 176 patients had R/R AML. Data reported include patients receiving enasidenib at total daily doses ranging from 50 mg to 650 mg in the dose-escalation arm and 100 mg once daily in the Phase 1 expansion arms. A maximum tolerated dose was not reached. The median age of the patients enrolled in the study is 70 (ranging from 19-100). Patients with R/R AML received a median of two prior lines of therapy (ranging from one to 14).
The overall safety profile observed for enasidenib was consistent with previously reported data. Twenty-four percent of patients had treatment-related serious adverse events, notably IDH differentiation syndrome (8 percent), leukocytosis (4 percent), tumor lysis syndrome (3 percent) and hyperbilirubinemia (2 percent). The most common treatment-emergent adverse events were nausea (46 percent) hyperbilirubinemia (45 percent), diarrhea (40 percent) and fatigue (40 percent).
Data from 176 R/R AML patients with an IDH2 mutation demonstrated a 40.3 percent (71 of 176 patients) overall response rate, which was the primary endpoint of the study. Further, the complete response rate was 19.3 percent (34 of 176 patients). Median duration of response was 5.8 months for all patients who responded and 8.8 months for patients who achieved a complete response. Median time to first response was 1.9 months and median time to complete response was 3.8 months. Median overall survival for R/R AML patients as observed in the study was 9.3 months.
“In addition to the complete response in this study, we also observed changes in responses and hematologic parameters over time,” Dr. Eytan Stein, lead investigator and attending physician in the leukemia service at Memorial Sloan Kettering Cancer Center, stated in a press release. “This suggests that differentiation of myeloblasts—made possible by inhibition of mutated IDH2—may drive the clinical efficacy of enasidenib.”
“Targeting IDH mutations is thought to allow for the differentiation of malignant cells and introduces a new paradigm in the treatment of AML,” remarked Dr. Chris Bowden, chief medical officer of Agios. “These data show that IDH inhibition plays an important role in segments of AML and will continue to inform our research into this novel class of potential therapies.”