– Both Combination and Monotherapy Data Show 33A is Well-Tolerated with Rapid, High Remission Rates for AML Patients in Multiple Phase 1 Trials; Data Highlighted in Three Oral Presentations –
– Addition of 33A to Hypomethylating Agents in Frontline Older AML Results in 73 Percent Remission Rate, with 50 Percent of Those Remissions Negative for Minimal Residual Disease; Data Supportive of Phase 3 CASCADE Study –
SAN DIEGO, CA, USA I December 5, 2016 I Seattle Genetics, Inc. (Nasdaq: SGEN), a global biotechnology company, today highlighted three oral data presentations on vadastuximab talirine (SGN-CD33A; 33A) in patients with acute myeloid leukemia (AML) at the 58th American Society of Hematology (ASH) Annual Meeting and Exposition taking place in San Diego, California, December 3-6, 2016. The data included updated results from an ongoing phase 1 clinical trial evaluating 33A in combination with hypomethylating agents (HMAs; azacitidine, decitabine) in frontline older AML patients. Further oral presentations focused on results from phase 1 clinical trials evaluating 33A in three distinct settings, including 1) as monotherapy in newly diagnosed older AML patients, 2) in combination with high-dose cytarabine for younger AML patients in first remission and 3) as monotherapy maintenance for younger AML patients who have completed frontline therapy or after allogeneic stem cell transplant. 33A is an investigational antibody-drug conjugate (ADC) targeted to CD33, a protein which is expressed on leukemic cells in nearly all AML patients.
Seattle Genetics is broadly evaluating 33A across multiple lines of therapy in patients with myeloid malignancies. In addition to the clinical trials presented at ASH this year, 33A is currently being evaluated in combination with HMAs in the ongoing global phase 3 CASCADE study. This trial is randomized, double-blind, and being conducted at multiple centers globally to evaluate if 33A in combination with azacitidine or decitabine can extend overall survival compared to azacitidine or decitabine alone in approximately 500 older patients with newly diagnosed AML. Additional phase 1 and 2 clinical trials for frontline younger AML and frontline myelodysplastic syndrome (MDS) are also underway. More information about 33A and ongoing clinical trials can be found at www.ADC-CD33.com.
“We are pleased with the growing body of data demonstrating that vadastuximab talirine, also known as 33A, has a promising overall tolerability and activity profile in clinical trials for patients with AML,” said Jonathan Drachman, M.D., Chief Medical Officer and Executive Vice President, Research and Development at Seattle Genetics. “We are committed to improving the therapeutic options for AML patients through innovative, targeted approaches. Our most advanced 33A clinical study, CASCADE, is a randomized phase 3 trial designed to test 33A in combination with hypomethylating agents, or HMAs, in approximately 500 older patients with newly diagnosed AML. Based on the encouraging data presented at ASH, we believe 33A has the potential for clinical development in multiple AML settings, with the goal of providing new treatment options for patients struggling with this aggressive and life-threatening disease.”
“AML therapy has not meaningfully changed over the past 40 years, and there is a dire need for improved treatment options. Older AML patients have a particularly poor prognosis with the standard of care, hypomethylating agents or HMAs,” said Amir Fathi, M.D., Massachusetts General Hospital Cancer Center. “I am pleased with the balance of activity and tolerability we have observed in phase 1 clinical trials evaluating 33A both as monotherapy and combination therapy in AML patients. For older patients with newly diagnosed AML, the 73 percent remission rate of 33A in combination with HMAs, with 50 percent of those patients negative for minimal residual disease, signals promise in improving long-term outcomes.”
The following data from the ongoing phase 1 studies evaluating 33A combination therapy or monotherapy in AML patients were presented:
Vadastuximab Talirine Plus Hypomethylating Agents: A Well-Tolerated Regimen with High Remission Rate in Frontline Older Patients With Acute Myeloid Leukemia (Abstract #591, oral presentation on Monday, December 5, 2016 at 7:30 a.m. PT)
Outcomes for AML patients who are older or ineligible to receive standard chemotherapy remain poor. HMAs are frequently used in this setting, but efficacy is limited. Updated results from an ongoing phase 1 study evaluating 33A in combination with HMAs (either azacitidine or decitabine) in newly diagnosed older AML patients were presented by Dr. Amir Fathi, Massachusetts General Hospital Cancer Center.
Data were reported from 53 frontline AML patients with a median age of 75 years and predominantly intermediate or adverse cytogenetic risk who had declined intensive therapy. Regarding additional poor-prognosis indicators, 42 percent of patients had evidence of underlying myelodysplasia, 11 percent had FLT3-mutated disease and 43 percent had secondary AML, which is AML that arises from prior chemotherapy, a pre-existing MDS or myeloproliferative disease. Key findings include:
- Of 49 patients evaluable for response, complete remission (CR) or CR with incomplete platelet or neutrophil recovery (CRi) was observed in 36 patients (73 percent).
- Remissions were observed in higher-risk patients, including 17 of 22 patients (77 percent) with secondary AML, five of five patients (100 percent) who were FLT3/ITD positive and 17 of 26 patients (65 percent) age 75 or older.
- Eighteen of the 36 patients (50 percent) who achieved remission (CR or CRi) were negative for minimal residual disease (MRD), which means no cancer could be detected with a sensitive test.
- With a median follow-up of 14.7 months, median overall survival for all patients was 11.3 months and 28 percent of patients remained alive and on study as of last follow-up. The 30- and 60-day mortality rates were two and eight percent, with no treatment-related deaths occurring during that time.
- For patients who achieved MRD-negative remission, the median survival had not yet been reached.
- The most common Grade 3 or 4 treatment-emergent adverse events occurring in 20 percent or more of patients were thrombocytopenia, febrile neutropenia, anemia and neutropenia.
- The most common Grade 1 and 2 treatment-emergent adverse events occurring in 20 percent or more of patients were fatigue, nausea, constipation, peripheral edema and decreased appetite.
Vadastuximab Talirine Monotherapy in Older Patients with Treatment Naive CD33-Positive Acute Myeloid Leukemia (Abstract #590, oral presentation on Monday, December 5, 2016 at 7:15 a.m. PT)
Interim results from 93 patients in the ongoing phase 1 study evaluating 33A monotherapy in AML patients were previously presented at the 2015 ASH Annual Meeting. New results describing the safety and activity of the recommended 33A monotherapy dose of 40 micrograms per kilogram (mcg/kg) in an expansion cohort of treatment-naïve older AML patients were presented by Dr. Anjali Advani, Cleveland Clinic.
Data were reported from 27 treatment-naïve older AML patients with a median age of 74 years and intermediate or adverse cytogenetic risk of 70 percent and 26 percent, respectively. Regarding additional poor-prognosis indicators, 48 percent of patients had evidence of underlying myelodysplasia and 22 percent had FLT3 mutated disease. Key findings include:
- Of the 26 patients evaluable for response, remission (CR or CRi) was observed in 15 patients (58 percent), with a median time to remission of 1.4 months.
- Forty-three percent of patients who achieved remission were MRD negative.
- Responses were observed in higher-risk patients, with remissions achieved in seven of 12 patients (58 percent) with underlying myelodysplasia and three of four patients (75 percent) who were positive for FLT3/ITD.
- The 30- and 60-day mortality rates were zero and 15 percent, respectively. The median overall survival for all patients was seven months.
- The most common Grade 3 or higher treatment-emergent adverse events occurring in 20 percent or more of patients were thrombocytopenia, febrile neutropenia and anemia.
- The most common Grade 1 and 2 treatment-emergent adverse events occurring in 20 percent or more of patients were peripheral edema, decreased appetite, fatigue, diarrhea and dizziness.
A Phase 1b Study of Vadastuximab Talirine as Maintenance and in Combination with Standard Consolidation for Patients with Acute Myeloid Leukemia (Abstract #340, oral presentation on Sunday, December 4, 2016 at 10:15 a.m. PT)
Interim results from an ongoing phase 1b study evaluating 33A in the AML post-remission setting, as a single agent for maintenance therapy or in combination with consolidation therapy (high-dose cytarabine; HiDAC), were presented by Dr. Jay Yang, Karmanos Cancer Institute.
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 therapies 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.
About Seattle Genetics
Seattle Genetics is an innovative biotechnology company that develops and commercializes novel antibody-based therapies for the treatment of cancer. The company’s industry-leading antibody-drug conjugate (ADC) technology harnesses the targeting ability of antibodies to deliver cell-killing agents directly to cancer cells. ADCETRIS® (brentuximab vedotin), the company’s lead product, in collaboration with Takeda Pharmaceutical Company Limited, is the first in a new class of ADCs commercially available globally in 65 countries for relapsed classical Hodgkin lymphoma (HL) and relapsed systemic anaplastic large cell lymphoma (sALCL). Seattle Genetics is also advancing vadastuximab talirine (SGN-CD33A; 33A), an ADC in a phase 3 trial for acute myeloid leukemia. Headquartered in Bothell, Washington, Seattle Genetics has a robust pipeline of innovative therapies for blood-related cancers and solid tumors designed to address significant unmet medical needs and improve treatment outcomes for patients. The company has collaborations for its proprietary ADC technology with a number of companies including AbbVie, Astellas, Bayer, Celldex, Genentech, GlaxoSmithKline and Pfizer. More information can be found at www.seattlegenetics.com.
SOURCE: Seattle Genetics
