On December 3, 2016 Seattle Genetics, Inc. (NASDAQ: SGEN), a global biotechnology company, reported phase 1b data evaluating vadastuximab talirine (SGN-CD33A; 33A) in combination with the frontline standard of care regimen for induction (cytarabine and daunorubicin, also known as 7+3) for younger patients with newly diagnosed acute myeloid leukemia (AML) in an oral presentation at the 58th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition taking place in San Diego, California, December 3-6, 2016 (Press release, Seattle Genetics, DEC 3, 2016, View Source [SID1234516877]). The data were also featured in an ASH (Free ASH Whitepaper) press program and selected to be included in the 2017 Highlights of ASH (Free ASH Whitepaper) post-meeting program. 33A is an investigational antibody-drug conjugate (ADC) targeted to CD33, a protein which is expressed on leukemic cells in nearly all AML patients. Schedule your 30 min Free 1stOncology Demo! "Our clinical trial data reported at ASH (Free ASH Whitepaper) demonstrate that adding vadastuximab talirine, also known as 33A, to standard of care treatment results in a rapid, high rate of remissions in frontline, younger AML patients with poor prognosis. Notably, seventy-eight percent of patients who achieved remissions in this trial tested negative for minimal residual disease, which means no cancer could be detected with a sensitive test," said Jonathan Drachman, M.D., Chief Medical Officer and Executive Vice President, Research and Development at Seattle Genetics. "In this trial, 33A in combination with 7+3 was well-tolerated, with a low early mortality rate. Based on these promising, early data, we plan to initiate a randomized phase 2 clinical trial in 2017 in younger newly diagnosed AML patients to further evaluate the potential benefit of adding 33A to standard of care."
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"People with acute myeloid leukemia die of infections or bleeding within weeks or a few months of diagnosis without effective, aggressive chemotherapy. Even with current treatment regimens, fewer than 50% of younger adults are successfully treated. The phase 1 results of 33A in combination with standard of care show a high rate of remissions in younger newly diagnosed AML patients without significantly adding to the toxicity of the treatment. Notably, 94 percent of remissions occur with only one cycle of treatment," said Harry P. Erba, M.D., Ph.D., University of Alabama-Birmingham and presenter of the phase 1 data at ASH (Free ASH Whitepaper). "Furthermore, the majority of these patients have no evidence of disease following the 33A combination even using a very sensitive test for residual leukemia (minimal residual disease negative). The rate at which patients become minimal residual disease negative following 33A combination treatment offers encouraging preliminary evidence that 33A in combination with 7+3 could reduce relapse rates and improve long-term outcomes for these patients."
The following interim results from the ongoing phase 1 study evaluating 33A in combination with 7+3 in frontline AML will be presented by Dr. Harry P. Erba, University of Alabama-Birmingham, in an oral session on Saturday, December 3, 2016:
A Phase 1b Study of Vadastuximab Talirine in Combination with 7+3 Induction Therapy for Patients with Newly Diagnosed Acute Myeloid Leukemia (AML) (Abstract #211, oral presentation on Saturday, December 3, 2016 at 4:00 p.m. PT)
Data were reported from 42 newly diagnosed AML patients with a median age of 46 years and intermediate or adverse cytogenetic risk of 50 percent and 36 percent, respectively. Seventeen percent of patients had secondary AML. Key findings include:
Of 42 patients evaluable for response, 32 patients (76 percent) achieved a complete remission (CR) or complete remission with incomplete platelet or neutrophil recovery (CRi). Ninety-four percent of the remissions (CR or CRi) occurred with one cycle of therapy.
Twenty-five of the 32 patients (78 percent) who achieved remission were negative for minimal residual disease (MRD). MRD-negative remission post-induction is generally correlated with reduced rates of relapse and improved overall survival.
Remissions were observed in higher-risk patients, including 18 of 21 (86 percent) and nine of 15 (60 percent) patients with intermediate or adverse cytogenetics, respectively.
Overall survival (OS) is still evolving and median OS has not yet been reached. The 30-day mortality rate was two percent. Twenty-one of 42 patients (50 percent) went on to receive an allogenic stem cell transplant.
The most common Grade 3 or 4 treatment-emergent adverse events occurring in 20 percent or more of patients were febrile neutropenia, thrombocytopenia, anemia and neutropenia. No non-hematologic treatment-emergent adverse events of Grade 3 or higher were reported in 15 percent or more of patients. No veno-occlusive disease/sinusoidal obstruction syndrome or significant hepatotoxicity was observed on treatment.
The most common Grade 1 and 2 treatment-emergent adverse events occurring in 20 percent or more of patients were nausea, diarrhea, constipation, hypokalemia and decreased appetite. No infusion-related reactions occurred.
This phase 1 study continues to enroll patients. A randomized phase 2 trial of 33A plus 7+3 versus 7+3 alone is planned.
Seattle Genetics is broadly evaluating 33A across multiple lines of therapy in patients with myeloid malignancies. The ongoing global phase 3 CASCADE study is a randomized, double-blind, multi-center trial designed to evaluate 33A in combination with hypomethylating agents (HMAs) in approximately 500 previously untreated AML patients. Further, phase 1 and 2 clinical trials for relapsed AML and for previously untreated myelodysplastic syndrome (MDS) are currently underway. More information about 33A and ongoing clinical trials can be found at www.ADC-CD33.com.
About Acute Myeloid Leukemia
Acute myeloid leukemia, also called acute myelocytic leukemia or AML, is an aggressive cancer of the bone marrow and blood that progresses rapidly without treatment. Cancerous cells called leukemic blasts multiply and crowd out normal cells in the bone marrow and interfere with normal blood cell production leading to anemia, infection, and bleeding. According to the SEER database and Kantar Health Sciences, in 2016 approximately 33,000 new cases of AML (mostly in adults) will be diagnosed in the U.S. and Europe. In the U.S. alone, nearly 10,500 deaths will occur from AML this year. Treatment options for AML have remained virtually unchanged for nearly 40 years and frontline treatment consists primarily of chemotherapy. A subset of patients (typically those over 60 years of age) cannot tolerate such therapy and are typically given lower intensity agents, supportive care, or are recommended for clinical trials.
About Vadastuximab Talirine (SGN-CD33A)
Vadastuximab talirine (SGN-CD33A; 33A) is a novel investigational ADC targeted to CD33 utilizing Seattle Genetics’ proprietary ADC technology. CD33 is expressed on most AML and MDS blast cells. The CD33 engineered cysteine antibody is stably linked to a highly potent DNA binding agent called a pyrrolobenzodiazepine (PBD) dimer via site-specific conjugation technology (EC-mAb). PBD dimers are significantly more potent than systemic chemotherapeutic drugs and the EC-mAb technology allows uniform drug-loading onto an ADC. The ADC is designed to be stable in the bloodstream and to release its potent cell-killing PBD agent upon internalization into CD33-expressing cells.
33A was granted Orphan Drug Designation by both the U.S. Food and Drug Administration (FDA) and the European Commission for the treatment of AML. FDA orphan drug designation is intended to encourage companies to develop therapies for the treatment of diseases that affect fewer than 200,000 individuals in the United States.