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Seattle Genetics Initiates Phase 2 Clinical Trial of Denintuzumab Mafodotin (SGN-CD19A) Combination Therapy in Relapsed or Refractory Diffuse Large B-cell Lymphoma (DLBCL)

-Trial Based on Data From Phase 1 Trial in B-cell Non-Hodgkin Lymphoma-

BOTHELL, Wash.--(BUSINESS WIRE)--Oct. 29, 2015-- Seattle Genetics, Inc. (NASDAQ:SGEN) today announced the initiation of a randomized phase 2 clinical trial of denintuzumab mafodotin (SGN-CD19A) in combination with the second-line salvage regimen of rituximab (Rituxan), ifosfamide, carboplatin and etoposide (RICE), for patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). DLBCL is the most common type of aggressive non-Hodgkin lymphoma. The study is intended to evaluate the activity and safety of the combination regimen compared to RICE alone. Denintuzumab mafodotin is an antibody-drug conjugate (ADC) targeting CD19, a protein expressed uniformly on almost all B-cell malignancies. The ADC is designed to be stable in the bloodstream and release its cytotoxic agent upon internalization into CD19-expressing cells. This approach is intended to spare non-targeted cells and thus reduce many of the toxic effects associated with traditional chemotherapy while enhancing antitumor activity.

“The only curative option for patients with diffuse large B-cell lymphoma, or DLBCL, who relapse after initial treatment is an intensive salvage regimen with the goal of achieving the best possible response prior to autologous stem cell transplant. Those who are transplanted in PET-negative complete remission have the best outcomes. Currently, only 50 percent of DLBCL patients are able to proceed to a transplant following treatment with any of the currently available salvage treatment regimens, representing a significant need to identify more effective treatment options,” said Jonathan Drachman, M.D., Chief Medical Officer and Executive Vice President, Research and Development at Seattle Genetics. “In relapsed DLBCL patients in a phase 1 clinical trial, we have observed an objective response rate over 50 percent with denintuzumab mafodotin monotherapy and a tolerability profile that is well suited to combination regimens. Our preclinical data suggest that combining denintuzumab mafodotin with RICE may result in synergistic activity, potentially leading to improved treatment outcomes in relapsed or refractory DLBCL patients.”

In this phase 2 randomized, open-label, multi-center clinical trial, approximately 150 relapsed/refractory DLBCL or grade 3B follicular lymphoma patients who are eligible for an autologous stem cell transplant (ASCT) will be randomized to receive RICE either with or without denintuzumab mafodotin every three weeks for three cycles. The primary endpoint is to compare the complete remission rates between the two study arms. Secondary endpoints include safety of the combination regimen, progression-free survival, overall survival and the number of patients who are able to undergo autologous transplant.

At the 2014 American Society of Hematology (ASH) Annual Meeting, data were presented from an ongoing phase 1 trial of relapsed/refractory aggressive non-Hodgkin lymphoma patients who received single-agent denintuzumab mafodotin every three weeks. Of the 51 evaluable patients, including 45 DLBCL patients, the objective response rate across all dose levels was 35 percent, including 20 percent complete remissions and 16 percent partial remissions. In the subset of patients who had relapsed disease, the objective response rate was 55 percent, including 32 percent complete remissions and 23 percent partial remissions. The most common adverse events of any grade occurring in more than 25 percent of patients were blurred vision (60 percent), dry eye (46 percent), fatigue (38 percent), constipation (33 percent) and keratopathy (31 percent). Ocular symptoms and corneal findings were superficial, generally reversible, and were managed with steroid eye drop treatment and dose modifications. The majority of affected patients experienced improvement and/or resolution at last follow up. Furthermore, no significant myelosuppression or peripheral neuropathy were observed, suggesting that denintuzumab mafodotin may be well tolerated in combination with multi-agent chemotherapy.

For more information about the denintuzumab mafodotin phase 2 DLBCL clinical trial, including enrolling centers, visit www.clinicaltrials.gov.

About Lymphoma

Lymphoma is a general term for a group of cancers that originate in the lymphatic system. There are two major categories of lymphoma: Hodgkin lymphoma and non-Hodgkin lymphoma. Non-Hodgkin lymphoma represents a diverse group of cancers that develop in the lymphatic system and are characterized by uncontrolled growth and accumulation of abnormal lymphocytes. Lymphocytes are a type of blood cells that are responsible for defending the body against infection. The most common forms of non-Hodgkin lymphoma are diffuse large B-cell lymphoma (an aggressive subtype) and follicular lymphoma (an indolent subtype).

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 a CD30-targeted ADC that, in collaboration with Takeda Pharmaceutical Company Limited, is commercially available in more than 55 countries, including the U.S., Canada, Japan and members of the European Union. Additionally, ADCETRIS is being evaluated broadly in more than 30 ongoing clinical trials in CD30-expressing malignancies. Seattle Genetics is also advancing a robust pipeline of clinical-stage programs, including denintuzumab mafodotin, SGN-CD33A, SGN-LIV1A, SGN-CD70A, ASG-22ME, ASG-15ME and SEA-CD40. 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.

Forward-Looking Statement:

Certain of the statements made in this press release are forward-looking, such as those, among others, relating to the therapeutic potential of denintuzumab mafodotin in treating patients with DLBCL and expected conduct of the Phase 2 clinical study including anticipated number of patients and clinical sites. 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 risks of adverse events associated with denintuzumab mafodotin use, negative or unexpected denintuzumab mafodotin clinical trial results even after promising results in earlier company-sponsored trials, and adverse regulatory actions affecting denintuzumab mafodotin. More information about the risks and uncertainties faced by Seattle Genetics is contained under the caption “Risk Factors” included in Exhibit 99.1 to the company’s Current Report on Form 8-K filed with the Securities and Exchange Commission on September 9, 2015. 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.

Source: Seattle Genetics, Inc.

Seattle Genetics, Inc.
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