Seattle Genetics and Bristol-Myers Squibb Highlight First Data from Phase 1/2 Study Evaluating ADCETRIS® (Brentuximab Vedotin) in Combination with Opdivo (nivolumab) in Relapsed or Refractory Hodgkin Lymphoma at ASH Annual Meeting

– Combination Data Showed 90 Percent Objective Response Rate and 62 Percent Complete Response Rate with an Acceptable Safety Profile in Pre-Transplant Relapsed or Refractory Classical Hodgkin Lymphoma Patients –

– Data Support Continued Clinical Investigation of ADCETRIS and Opdivo Combination in Hodgkin Lymphoma –

SAN DIEGO, CA, USA I December 5, 2016 I Seattle Genetics, Inc. (NASDAQ:SGEN) and Bristol-Myers Squibb Company (NYSE:BMY) today highlighted the first reported data from an ongoing phase 1/2 clinical trial evaluating ADCETRIS (brentuximab vedotin) in combination with Opdivo (nivolumab) in relapsed or refractory classical Hodgkin lymphoma (HL) at the 58th American Society of Hematology (ASH) Annual Meeting and Exposition taking place in San Diego, California, December 3-6, 2016. The data reported from 42 patients, including 29 evaluable for response, were featured in an oral presentation and selected to be included in the 2017 Highlights of ASH post-meeting program. ADCETRIS is an antibody-drug conjugate (ADC) directed to CD30, a defining marker of classical HL that plays a role in tumor growth and survival. Opdivo is a programmed death-1 (PD-1) immune checkpoint inhibitor that is designed to harness the body’s own immune system to help restore anti-tumor immune response. ADCETRIS and Opdivo are not approved in combination for the treatment of relapsed or refractory HL or for other indications.

“The phase 1/2 study combining the antibody-drug conjugate ADCETRIS with the PD-1 immune checkpoint inhibitor Opdivo is a promising investigational approach as it combines a targeted therapy with a therapy designed to activate the immune system and the combination may have synergistic activity,” said Alex Herrera, M.D., lead trial investigator and assistant professor at the City of Hope Medical Center, Duarte, California. “The preliminary results are compelling and support further exploration of this novel regimen, free of traditional chemotherapy.”

“We are evaluating ADCETRIS broadly as the foundation of care for CD30-expressing lymphomas, including combination strategies that have the potential to improve efficacy,” said Jonathan Drachman, M.D., Chief Medical Officer and Executive Vice President, Research and Development at Seattle Genetics. “Preliminary data from the trial evaluating ADCETRIS in combination with Opdivo as pre-transplant salvage therapy for classical HL patients demonstrate a 90 percent objective response rate, with a 62 percent complete response rate and an acceptable safety profile. We look forward to further evaluation of this innovative combination regimen in other disease settings, including frontline older HL patients and CD30-expressing non-Hodgkin lymphoma, in partnership with Bristol-Myers Squibb.”

Fouad Namouni, M.D., Head of Development, Oncology, Bristol-Myers Squibb, commented, “With these new data presented at ASH, Bristol-Myers Squibb continues its efforts to strengthen its broad Immuno-Oncology and hematology development programs for Opdivo. Through our continued partnership with Seattle Genetics, we hope to build on the significant progress we’ve made with Opdivo as monotherapy and deliver new combination treatment options with the potential to improve the lives of patients impacted by blood cancers with high unmet needs.”

Preliminary Results from a Phase 1/2 Study of Brentuximab Vedotin in Combination with Nivolumab in Patients with Relapsed or Refractory Hodgkin Lymphoma (Abstract #1105, oral presentation at 4:30 p.m. PT)

Data were reported from 42 patients with relapsed or refractory HL after failure of frontline therapy who received the combination regimen of ADCETRIS plus Opdivo. Patients were treated once every three weeks with up to four cycles of combination therapy. After completion of the fourth cycle of treatment, patients were eligible to undergo an autologous stem cell transplant (ASCT). The median age of patients was 37 years. The majority of patients (88 percent) were refractory or had progressed after receiving the standard of care frontline treatment ABVD (Adriamycin, bleomycin, vinblastine and dacarbazine).

Key findings presented include:

  • Of 29 response-evaluable patients, 26 patients (90 percent) had an objective response, including 18 patients (62 percent) with a complete metabolic response and eight patients (28 percent) with a partial metabolic response. One patient (three percent) had stable disease and two patients (seven percent) had progressive disease.
  • Of the 42 patients enrolled, all patients (100 percent) received one or more dose of the study therapies, 12 patients (29 percent) remain on treatment, 28 patients (67 percent) have completed treatment and two patients (five percent) discontinued prior to the end of treatment. At the time of data analysis in the ongoing trial, nine patients (21 percent) initiated an ASCT and two patients (five percent) received an alternative salvage therapy prior to ASCT. Preliminary analysis shows no impact of ADCETRIS and Opdivo combination on stem cell mobilization or engraftment.
  • The median number of doses administered for both ADCETRIS and Opdivo was four. Of the 42 patients, no patients had a dose reduction during treatment due to an adverse event for either therapy. Dose delays occurred for three patients (seven percent) with ADCETRIS treatment and four patients (10 percent) with Opdivo treatment. Reasons for dose delays were urticaria, thrombosis, elevated lipase, chills and hypoxia.
  • The most common adverse events of any grade occurring prior to ASCT in more than 20 percent of patients were fatigue, nausea, infusion related reaction, pruritus and rash. One patient had a treatment-related serious adverse event after Cycle 1 of ADCETRIS, with Grade 3 dehydration, Grade 1 asthenia and nausea, Grade 2 hypercalcemia and malaise.
  • Infusion-related reactions (IRR) were observed in 38 percent of patients and most symptoms included flushing and nausea (14 percent each); chest discomfort, dyspnea, urticaria (12 percent each); cough and pruritis (10 percent each). A protocol amendment was made requiring premedication with low-dose corticosteroids and antihistamine. No patients discontinued treatment due to an IRR.
  • Potential immune-related adverse events included IRR (36 percent [one IRR not reported as associated with infusion]; Grade 1 or 2), rash (29 percent; Grade 1 or 2), diarrhea (26 percent; Grade 1 or 2), transaminase elevation (10 percent; Grade 1 and 3/4) and hypothyroidism (five percent; Grade 2). There were no occurrences of pneumonitis or colitis.

ADCETRIS and Opdivo are being evaluated as combination therapy in multiple ongoing phase 1/2 clinical trials. In addition to the study presented at ASH, a trial titled “A Safety and Effectiveness Study of Nivolumab in Combination With Brentuximab Vedotin to Treat Non-Hodgkin Lymphomas” is ongoing and focused on patients with relapsed or refractory disease, including diffuse large B-cell lymphoma (DLBCL), and other rare subtypes of B-cell, including mediastinal B-cell lymphoma and mediastinal gray zone lymphoma. In addition, the companies recently extended the clinical evaluation of ADCETRIS and Opdivo into a clinical trial evaluating the combination as frontline treatment for older HL patients.

About Classical Hodgkin Lymphoma

Lymphoma is a general term for a group of cancers that originate in the lymphatic system and is the most common type of blood cancer. There are two major categories of lymphoma: HL, also known as Hodgkin disease, and non-Hodgkin lymphoma. HL is a cancer that starts in white blood cells called lymphocytes, which are part of the body’s immune system. The disease is most often diagnosed in early adulthood (ages 20-40) and late adulthood (older than 55 years of age). Classical Hodgkin lymphoma is the most common type of HL, accounting for 95% of cases. Classical HL is distinguished from other lymphomas by the characteristic presence of CD30-positive Reed-Sternberg cells.

According to the American Cancer Society, approximately 8,500 cases of HL will be diagnosed in the United States during 2016 and more than 1,100 will die from the disease. According to the Lymphoma Coalition, over 62,000 people worldwide are diagnosed with HL each year and approximately 25,000 people die each year from this cancer. In the European Union, about 12,200 new cases and 2,600 deaths occurred in 2012 as a result of HL.

About ADCETRIS (Brentuximab Vedotin)

ADCETRIS is being evaluated broadly in more than 70 ongoing clinical trials, including three phase 3 studies, the ongoing ECHELON-1 trial in frontline classical Hodgkin lymphoma and the ongoing ECHELON-2 trial in frontline mature T-cell lymphomas, as well as the completed ALCANZA trial in cutaneous T-cell lymphoma for which a supplemental BLA is planned in the first half of 2017.

ADCETRIS is an ADC comprising an anti-CD30 monoclonal antibody attached by a protease-cleavable linker to a microtubule disrupting agent, monomethyl auristatin E (MMAE), utilizing Seattle Genetics’ proprietary technology. The ADC employs a linker system that is designed to be stable in the bloodstream but to release MMAE upon internalization into CD30-expressing tumor cells.

ADCETRIS for intravenous injection has received approval from the FDA for three indications: (1) regular approval for the treatment of patients with classical Hodgkin lymphoma after failure of autologous hematopoietic stem cell transplantation (auto-HSCT) or after failure of at least two prior multi-agent chemotherapy regimens in patients who are not auto-HSCT candidates, (2) regular approval for the treatment of classical Hodgkin lymphoma patients at high risk of relapse or progression as post-auto-HSCT consolidation, and (3) accelerated approval for the treatment of patients with systemic anaplastic large cell lymphoma (sALCL) after failure of at least one prior multi-agent chemotherapy regimen. The sALCL indication is approved under accelerated approval based on overall response rate. Continued approval for the sALCL indication may be contingent upon verification and description of clinical benefit in confirmatory trials. Health Canada granted ADCETRIS approval with conditions for relapsed or refractory Hodgkin lymphoma and sALCL.

ADCETRIS was granted conditional marketing authorization by the European Commission in October 2012 for two indications: (1) for the treatment of adult patients with relapsed or refractory CD30-positive Hodgkin lymphoma following autologous stem cell transplant (ASCT), or following at least two prior therapies when ASCT or multi-agent chemotherapy is not a treatment option, and (2) the treatment of adult patients with relapsed or refractory sALCL. The European Commission extended the current conditional approval of ADCETRIS and approved ADCETRIS for the treatment of adult patients with CD30-positive Hodgkin lymphoma at increased risk of relapse or progression following ASCT.

ADCETRIS has received marketing authorization by regulatory authorities in 65 countries. See important safety information below.

Seattle Genetics and Takeda are jointly developing ADCETRIS. Under the terms of the collaboration agreement, Seattle Genetics has U.S. and Canadian commercialization rights and Takeda has rights to commercialize ADCETRIS in the rest of the world. Seattle Genetics and Takeda are funding joint development costs for ADCETRIS on a 50:50 basis, except in Japan where Takeda is solely responsible for development costs.

About Opdivo

Opdivo is a programmed death-1 (PD-1) immune checkpoint inhibitor that is designed to uniquely harness the body’s own immune system to help restore anti-tumor immune response. By harnessing the body’s own immune system to fight cancer, Opdivo has become an important treatment option across multiple cancers.

Opdivo’s leading global development program is based on Bristol-Myers Squibb’s scientific expertise in the field of Immuno-Oncology and includes a broad range of clinical trials across all phases, including Phase 3, in a variety of tumor types. To date, the Opdivo clinical development program has enrolled more than 25,000 patients. The Opdivo trials have contributed to gaining a deeper understanding of the potential role of biomarkers in patient care, particularly regarding how patients may benefit from Opdivo across the continuum of PD-L1 expression.

In July 2014, Opdivo was the first PD-1 immune checkpoint inhibitor to receive regulatory approval anywhere in the world. Opdivo is currently approved in more than 57 countries, including the United States, the European Union and Japan. In October 2015, the company’s Opdivo + Yervoy combination was the first Immuno-Oncology combination to receive regulatory approval for the treatment of metastatic melanoma and is currently approved in more than 47 countries, including the United States and the European Union.

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 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, Genentech, GlaxoSmithKline and Pfizer. More information can be found at www.seattlegenetics.com

Bristol-Myers Squibb: At the Forefront of Immuno-Oncology Science & Innovation

At Bristol-Myers Squibb, patients are at the center of everything we do. Our vision for the future of cancer care is focused on researching and developing transformational Immuno-Oncology (I-O) medicines that will raise survival expectations in hard-to-treat cancers and will change the way patients live with cancer.

We are leading the scientific understanding of I-O through our extensive portfolio of investigational and approved agents, including the first combination of two I-O agents in metastatic melanoma, and our differentiated clinical development program, which is studying broad patient populations across more than 20 types of cancers with 11 clinical-stage molecules designed to target different immune system pathways. Our deep expertise and innovative clinical trial designs uniquely position us to advance the science of combinations across multiple tumors and potentially deliver the next wave of I-O combination regimens with a sense of urgency. We also continue to pioneer research that will help facilitate a deeper understanding of the role of immune biomarkers and inform which patients will benefit most from I-O therapies.

We understand making the promise of I-O a reality for the many patients who may benefit from these therapies requires not only innovation on our part but also close collaboration with leading experts in the field. Our partnerships with academia, government, advocacy and biotech companies support our collective goal of providing new treatment options to advance the standards of clinical practice.

About the Bristol-Myers Squibb and Ono Pharmaceutical Collaboration

In 2011, through a collaboration agreement with Ono Pharmaceutical Co., Ltd (Ono), Bristol-Myers Squibb expanded its territorial rights to develop and commercialize Opdivo globally except in Japan, South Korea and Taiwan, where Ono had retained all rights to the compound at the time. On July 23, 2014, Bristol-Myers Squibb and Ono further expanded the companies’ strategic collaboration agreement to jointly develop and commercialize multiple immunotherapies – as single agents and combination regimens – for patients with cancer in Japan, South Korea and Taiwan.

About Bristol-Myers Squibb

Bristol-Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information about Bristol-Myers Squibb, visit us at BMS.com or follow us on LinkedIn, Twitter, YouTube and Facebook.

SOURCE: Bristol-Myers Squibb

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