Seattle Genetics, Inc. (Nasdaq: SGEN) today presented interim phase 1 clinical data from SGN-CD19A, an antibody-drug conjugate (ADC) in development for the treatment of B-cell malignancies, including acute lymphoblastic leukemia (ALL), at the 55 th American Society of Hematology (ASH) Annual Meeting and Exposition taking place in New Orleans, Louisiana, December 7-10, 2013. SGN-CD19A is an ADC targeting CD19, a protein expressed uniformly on almost all B-cell malignancies. ADCs are monoclonal antibodies that are designed to selectively deliver cytotoxic agents to tumor cells. This approach is intended to spare non-targeted cells and thus reduce many of the toxic effects of traditional chemotherapy while enhancing antitumor activity. “The phase 1 trial evaluating SGN-CD19A has demonstrated encouraging early antitumor activity and a generally well-tolerated safety profile among heavily pretreated patients with acute lymphoblastic leukemia and very aggressive types of lymphoma. In addition, multiple complete remissions have been observed in a parallel phase 1 study evaluating SGN-CD19A in aggressive non-Hodgkin lymphoma. Dose-escalation is ongoing in both phase 1 clinical trials, and we plan to report additional data during 2014,” said Jonathan Drachman, M.D., Chief Medical Officer and Executive Vice President, Research and Development at Seattle Genetics. “Across our six internal clinical development-stage ADCs and more than a dozen collaborator programs, our industry-leading technology continues to empower innovative candidates in development as potential treatment options for patients.” With over a decade of experience and knowledge in ADC innovation, Seattle Genetics is the leader in developing ADCs, a technology designed to harness the targeting ability of antibodies to deliver cell-killing agents directly to cancer cells. Of the approximately 30 ADC candidates in clinical development across the biotechnology and pharmaceutical industry, more than 18 utilize Seattle Genetics’ proprietary ADC technology. A First-in-Human Phase 1 Study of the Antibody-Drug Conjugate SGN-CD19A in Relapsed or Refractory B-Lineage Acute Leukemia and Highly Aggressive Lymphoma (Abstract #1437) Data were reported from 16 adult patients and four pediatric patients with relapsed or refractory B-lineage ALL and highly aggressive lymphoma, including B-cell lymphoblastic lymphoma (B-LBL) and Burkitt lymphoma. The median age of adult patients was 46 years and the median number of prior systemic therapies was two, with six patients (38 percent) having received a prior allogeneic stem cell transplant. The median age of pediatric patients was 14 years and the median number of prior systemic therapies was three, with two patients (50 percent) having received a prior allogeneic stem cell transplant.
The primary endpoints of the ongoing clinical trial are to estimate the maximum tolerated dose and to evaluate the safety of SGN-CD19A. In addition, the trial is evaluating antitumor activity, pharmacokinetics, progression-free survival and overall survival. In this dose-escalation study, patients receive SGN-CD19A on days one and eight of every 21-day cycle. Key findings presented by Dr. Uma Borate from The University of Alabama in Birmingham, AL, included:
- At the time of data analysis, the maximum tolerated dose had not yet been reached. Enrollment and dose escalation are ongoing.
- Of the 16 adult patients treated across all dose levels, three (19 percent) achieved a complete remission or complete remission with incomplete platelet recovery, eight (50 percent) had resistant disease with clinical benefit or stable disease and five (31 percent) had progressive disease.
- At dose levels greater than 1.0 milligram per kilogram (mg/kg), eight of 10 adult patients had clinical benefit, consisting of complete remission, complete remission with incomplete platelet recovery, resistant disease with clinical benefit or stable disease.
- Of the four pediatric patients, one patient had resistant disease with clinical benefit, one had resistant disease without clinical benefit, one had progressive disease and one was unevaluable.
- The most common adverse events of any grade occurring in adult patients were fever (56 percent), nausea (44 percent), chills (38 percent), fatigue (38 percent), blurred vision (38 percent) and vomiting (38 percent). Adverse events seen in at least two pediatric patients (50 percent or more) were vomiting (three patients) and abdominal pain, cough, shortness of breath, nausea and fever (two patients each).
Preclinical data presented at the 2011 American Association for Cancer Research Annual Meeting demonstrated that SGN-CD19A effectively binds to target cells, internalizes and induces potent cell-killing activity and durable tumor regressions at low doses in multiple preclinical cancer models. SGN-CD19A is being evaluated in two ongoing phase 1 clinical trials for patients with B-cell ALL and aggressive non-Hodgkin lymphoma.About Acute Lymphoblastic Leukemia Acute lymphoblastic leukemia, also called acute lymphocytic leukemia or ALL, is an aggressive type of cancer of the bone marrow and blood that progresses rapidly without treatment. In ALL, lymphoblasts, which are malignant, immature white blood cells, multiply and crowd out normal cells in the bone marrow. ALL is the most common type of cancer in children. According to the American Cancer Society, approximately 6,000 people were diagnosed with ALL during 2012 and more than 1,400 died from the disease. About Seattle Genetics Seattle Genetics is a biotechnology company focused on the development and commercialization of innovative antibody-based therapies for the treatment of cancer. Seattle Genetics is leading the field in developing antibody-drug conjugates (ADCs), a technology designed to harness the targeting ability of antibodies to deliver cell-killing agents directly to cancer cells. The company’s lead product, ADCETRIS ® (brentuximab vedotin) is an ADC that, in collaboration with Takeda Pharmaceutical Company Limited, has been approved for two indications in more than 35 countries, including the U.S., European Union and Canada. Additionally, ADCETRIS is being evaluated broadly in more than 20 ongoing clinical trials. Seattle Genetics is also advancing a robust pipeline of clinical-stage ADC programs, including SGN-CD19A, SGN-CD33A, SGN-LIV1A, ASG-22ME and ASG-15ME. Seattle Genetics has collaborations for its ADC technology with a number of leading biotechnology and pharmaceutical companies, including AbbVie, Agensys (an affiliate of Astellas), Bayer, Genentech, GlaxoSmithKline and Pfizer. More information can be found at www.seattlegenetics.com. Certain of the statements made in this press release are forward looking, such as those, among others, relating to the therapeutic potential of SGN-CD19A. Actual results or developments may differ materially from those projected or implied in these forward-looking statements. Factors that may cause such a difference include the inability to show sufficient activity in these recently initiated clinical trials and the risk of adverse events as SGN-CD19A advances in clinical trials. More information about the risks and uncertainties faced by Seattle Genetics is contained in the company’s 10-Q for the quarter ended September 30, 2013 filed with the Securities and Exchange Commission. Seattle Genetics disclaims any intention or obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise.