Seattle Genetics Announces Multiple Data Presentations Evaluating ADCETRIS® (Brentuximab Vedotin) in Patients with Hodgkin Lymphoma at ISHL 2018

-Encore and Additional Analyses from Phase 3 ECHELON-1 Trial Evaluating ADCETRIS in Combination with Chemotherapy in Frontline Advanced HL-

-Interim Results from Ongoing Studies of ADCETRIS plus Opdivo^® (Nivolumab) in Frontline or Relapsed Hodgkin Lymphoma-

-Five-Year Results from Phase 3 AETHERA Trial of ADCETRIS as HL Post-Transplant Consolidation Therapy-

BOTHELL, Wash.--(BUSINESS WIRE)--Seattle Genetics, Inc. (Nasdaq:SGEN) today highlighted multiple presentations evaluating ADCETRIS (brentuximab vedotin) across a broad range of Hodgkin lymphoma (HL) settings at the 11^th International Symposium on Hodgkin Lymphoma (ISHL) taking place in Cologne, Germany, October 27-29, 2018. Data include both encore and additional analyses from the phase 3 ECHELON-1 clinical trial evaluating ADCETRIS in combination with chemotherapy in frontline Stage III or IV classical HL adult patients, which formed the basis of U.S. Food and Drug Administration (FDA) approval in this indication in March 2018. Interim results will be presented from two ongoing clinical trials evaluating ADCETRIS in combination with Opdivo (nivolumab), including in newly diagnosed older HL patients. Lastly, five-year follow-up from the phase 3 AETHERA clinical trial will be presented. ADCETRIS is an antibody-drug conjugate (ADC) directed to CD30, a defining marker of classical HL that plays a role in tumor pathogenesis. ADCETRIS is being evaluated globally as the foundation of therapy for HL in more than 50 ongoing clinical trials. ADCETRIS and Opdivo are not approved in combination for the treatment of HL.

“After more than a decade of dedicated clinical research with ADCETRIS, we have made significant progress in improving the treatment outcomes for patients with Hodgkin lymphoma,” said Nancy Whiting, Pharm.D., Senior Vice President, Clinical Development and Global Medical Affairs at Seattle Genetics. “At ISHL, we will present additional analyses from the ECHELON-1 trial, which demonstrated that ADCETRIS plus AVD improves upon a frontline standard of care regimen, ABVD, in advanced patients and resulted in the first change in advanced stage HL in over 40 years. In addition, three oral presentations will highlight ADCETRIS plus Opdivo combination data in frontline and relapsed/refractory HL and five-year data from the phase 3 AETHERA trial. We are pleased to share these results from our broad ADCETRIS clinical development program with the Hodgkin lymphoma community.”

Multiple corporate presentations will be presented at ISHL. Abstracts will be available at www.hodgkinsymposium.org.

Data from four analyses of the phase 3 ECHELON-1 clinical trial will be presented at ISHL. Importantly, an analysis from the ECHELON-1 study (Abstract #0038) will be presented in an oral presentation and poster showing PFS data per investigator that is consistent with the previously reported modified PFS data per Independent Review Facility (IRF). The ECHELON-1 abstracts include the following:

• Frontline brentuximab vedotin plus chemotherapy exhibits superior modified progression-free survival vs chemotherapy alone in patients with stage III or IV Hodgkin lymphoma: phase 3 ECHELON-1 study (Abstract #0038, oral presentation and poster on Monday, October 29 at 07:30-07:50 CEST)
• Population pharmacokinetic modeling and exposure-response assessment of brentuximab vedotin efficacy and safety in patients with advanced classical Hodgkin lymphoma from the phase 3 ECHELON-1 study (Abstract #0137, poster presentation)
• Serum sCD30 and TARC do not correlate with PET-based response assessment in patients (pts) with stage III or IV classical Hodgkin lymphoma (cHL): phase 3 ECHELON-1 study of brentuximab vedotin plus chemotherapy vs chemotherapy alone (Abstract #0159, poster presentation)
• Brentuximab vedotin plus chemotherapy in high risk advanced-stage classical Hodgkin lymphoma (cHL) patients: Results of pre-specified sub-group analyses from the ECHELON-1 study (Abstract #0136, poster presentation)

Additional data presentations at ISHL include the following:

Brentuximab Vedotin in Combination with Nivolumab in Patients with Relapsed or Refractory Hodgkin Lymphoma: Follow-up Results from the Phase 1/2 Study (Abstract #0005, oral presentation on Monday, October 29 at 14:40-14:50 CEST)

Data will be reported from 62 patients with relapsed or refractory HL who received the combination regimen of ADCETRIS plus Opdivo after failure of frontline therapy. Patients were treated once every three weeks, with up to four cycles of combination therapy in the outpatient setting. 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 (95 percent) were refractory or had relapsed after receiving the standard of care frontline treatment ABVD (Adriamycin, bleomycin, vinblastine and dacarbazine) or some variation of the standard of care (ABVE-PC, R-ABVD). Key findings will be presented in an oral presentation by Alex Herrera, M.D., Assistant Professor at the City of Hope Medical Center, Duarte, CA and include:

• Of 61 response-evaluable patients, 49 patients (80 percent) had an objective response, including 37 patients (61 percent) with a complete response and 12 patients (20 percent) with a partial response.
• Of the 61 response-evaluable patients, the estimated 21-month overall survival (OS) and PFS were 95 percent and 82 percent, respectively. The median follow-up time was 21.8 months and both median OS and PFS were not yet reached. Of 42 patients who underwent ASCT directly after treatment with ADCETRIS plus Opdivo, estimated PFS at 21-months was 97 percent and median PFS was not yet reached.
• PFS was evaluated by response to treatment. The estimated PFS at 21-months for patients with a complete response was 97 percent, for patients with a partial response was 83 percent and patients with stable disease was 50 percent.
• As previously reported, the most common adverse events (AEs) of any grade occurring prior to ASCT or subsequent salvage therapy in at least 20 percent of patients were nausea, infusion-related reaction (IRR), fatigue, pruritus, diarrhea, headache, vomiting, cough, pyrexia, dyspnea and nasal congestion.

Phase 2 Study of Frontline Brentuximab Vedotin Plus Nivolumab in Patients with Hodgkin Lymphoma Aged ≥60 Years (Abstract #0153, oral presentation on Monday, October 29 at 15:05-15:15 CEST)

Interim results will be presented from an ongoing phase 2 clinical trial evaluating ADCETRIS in combination with Opdivo as frontline therapy for HL patients age 60 years or older. ADCETRIS combination data were reported from 14 patients. The median age of patients was 71.5 years. The majority of patients (79 percent) had stage III/IV disease at the time of diagnosis. The interim results will be highlighted in an oral presentation by Jonathan Friedberg, M.D., Director of the University of Rochester Medical Center, NY and include:

• Of 11 response-evaluable patients with a median follow-up time of eight months, nine patients (82 percent) had an objective response, including six patients (55 percent) with a complete response and three patients (27 percent) with a partial response. In addition, two patients (18 percent) had stable disease which equates to all 11 patients (100 percent) experiencing disease control (complete response + partial response + stable disease) as a result of treatment with ADCETRIS in combination with Opdivo.
• The most common AEs of any grade occurring in at least 25 percent of patients were fatigue, diarrhea, constipation, nausea, arthralgia, chills, decreased appetite, pyrexia, IRR, aspartate aminotransferase increased and peripheral sensory neuropathy. Grade 3 or higher adverse events occurred in seven patients (50 percent), and the most common were peripheral neuropathy and lipase increased (three patients each); nausea and alanine aminotransferase increased (two patients each).
• Five patients (36 percent) had IRRs, with the majority of symptoms at Grade 1 and there were no Grade 3 or higher symptoms. Four patients (29 percent) were treated with corticosteroid and no patients discontinued treatment due to an IRR.

Five-Year Progression-Free Survival Outcomes from a Pivotal Phase 3 Study of Consolidative Brentuximab Vedotin after Autologous Stem-Cell Transplantation (ASCT) in Patients with Hodgkin Lymphoma at Risk of Relapse or Progression (AETHERA) (Abstract #0110, oral presentation on Monday, October 29 at 17:10-17:20 CEST)

The phase 3 AETHERA clinical trial was designed to evaluate the potential of single-agent ADCETRIS to extend PFS post-ASCT in patients with classical HL who were at high risk of relapse or progression. ADCETRIS was approved by the FDA in August 2015 for the treatment of adult patients with classical HL at high risk of relapse or progression as post-autologous hematopoietic stem cell transplantation (auto-HSCT) consolidation. The five-year follow-up efficacy and safety data will be highlighted in an oral presentation by Craig Moskowitz, M.D., Physician in Chief, Sylvester Comprehensive Cancer Center, University of Miami and include:

• The five-year PFS rate per investigator was 59 percent in the ADCETRIS arm compared to 41 percent in the placebo arm. Median PFS per investigator was not yet reached in the ADCETRIS arm versus 15.8 months in the placebo arm. The hazard ratio was 0.521 indicating a 48 percent reduction in the risk of progression or death with treatment of ADCETRIS compared to placebo.
• Fewer patients in the ADCETRIS arm of the study received subsequent anti-cancer therapies versus the placebo arm (32 percent versus 54 percent, respectively). In addition, fewer patients in the ADCETRIS arm received allogeneic stem-cell transplants versus the placebo arm (17 patients versus 31 patients).
• A PFS analysis evaluating subgroups included patients in the ADCETRIS arm with either two or more or three or more risk factors, showed patients with a greater number of risk factors for relapse post-ASCT appeared to have the greatest benefit from ADCETRIS consolidation therapy. In both subgroups evaluating either two or more or three or more risk factors, median PFS was not reached in the ADCETRIS arm and was 9.7 months and 6.3 months, respectively, in the placebo arm.
• In the ADCETRIS arm, 112 patients (67 percent) reported peripheral neuropathy. To date, 90 percent of these patients had resolution or improvement in symptoms, with 73 percent having complete resolution.

About Classical Hodgkin 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. Classical Hodgkin lymphoma is distinguished from other types of lymphoma by the presence of one characteristic type of cell, known as the Reed-Sternberg cell. The Reed-Sternberg cell expresses CD30.

According to the American Cancer Society, approximately 8,500 cases of Hodgkin lymphoma will be diagnosed in the United States during 2018 and more than 1,000 will die from the disease. Approximately half of all newly diagnosed Hodgkin lymphoma patients have Stage III/IV disease. According to the Lymphoma Coalition, over 62,000 people worldwide are diagnosed with Hodgkin lymphoma each year and approximately 25,000 people die each year from this cancer.

About ADCETRIS (brentuximab vedotin)

ADCETRIS is being evaluated broadly in more than 70 clinical trials in CD30-expressing lymphomas. These include the recently completed phase 3 ECHELON-2 trial in frontline peripheral T-cell lymphomas (also known as mature T-cell lymphoma), the completed phase 3 ECHELON-1 trial in previously untreated Hodgkin lymphoma, the completed phase 3 ALCANZA trial in cutaneous T-cell lymphoma, and the ongoing CHECKMATE 812 trial of ADCETRIS in combination with Opdivo (nivolumab) for relapsed/refractory Hodgkin lymphoma.

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 injection for intravenous infusion has received FDA approval for five indications in adult patients with: (1) previously untreated Stage III or IV classical Hodgkin lymphoma (cHL), in combination with chemotherapy, (2) cHL at high risk of relapse or progression as post-autologous hematopoietic stem cell transplantation (auto-HSCT) consolidation, (3) cHL after failure of auto-HSCT or failure of at least two prior multi-agent chemotherapy regimens in patients who are not auto-HSCT candidates, (4) sALCL after failure of at least one prior multi-agent chemotherapy regimen, and (5) primary cutaneous anaplastic large cell lymphoma (pcALCL) or CD30-expressing mycosis fungoides (MF) who have received prior systemic therapy.

Health Canada granted ADCETRIS approval with conditions for relapsed or refractory Hodgkin lymphoma and sALCL in 2013, and non-conditional approval for post-autologous stem cell transplantation (ASCT) consolidation treatment of Hodgkin lymphoma patients at increased risk of relapse or progression.

ADCETRIS received conditional marketing authorization from the European Commission in October 2012. The approved indications in Europe are: (1) for the treatment of adult patients with relapsed or refractory CD30-positive Hodgkin lymphoma following ASCT, or following at least two prior therapies when ASCT or multi-agent chemotherapy is not a treatment option, (2) the treatment of adult patients with relapsed or refractory sALCL, (3) for the treatment of adult patients with CD30-positive Hodgkin lymphoma at increased risk of relapse or progression following ASCT, and (4) for the treatment of adult patients with CD30-positive cutaneous T-cell lymphoma (CTCL) after at least one prior systemic therapy.

ADCETRIS has received marketing authorization by regulatory authorities in 71 countries for relapsed or refractory Hodgkin lymphoma and sALCL. See select important safety information, including Boxed Warning, 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 Seattle Genetics

Seattle Genetics, Inc. is an emerging multi-product, global biotechnology company that develops and commercializes transformative therapies targeting cancer to make a meaningful difference in people’s lives. ADCETRIS^® (brentuximab vedotin) utilizes the company’s industry-leading antibody-drug conjugate (ADC) technology and is currently approved for the treatment of multiple CD30-expressing lymphomas. Beyond ADCETRIS, the company has established a pipeline of novel targeted therapies at various stages of clinical testing, including three in ongoing pivotal trials for solid tumors. Enfortumab vedotin for metastatic urothelial cancer and tisotumab vedotin for metastatic cervical cancer utilize our proprietary ADC technology. Tucatinib, a small molecule tyrosine kinase inhibitor, is in a pivotal trial for HER2-positive metastatic breast cancer. In addition, we are leveraging our expertise in empowered antibodies to build a portfolio of proprietary immuno-oncology agents in clinical trials targeting hematologic malignancies and solid tumors. The company is headquartered in Bothell, Washington, and has a European office in Switzerland. For more information on our robust pipeline, visit www.seattlegenetics.com and follow @SeattleGenetics on Twitter.

ADCETRIS (brentuximab vedotin) U.S. Select Important Safety Information

BOXED WARNING: PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY (PML):

JC virus infection resulting in PML and death can occur in ADCETRIS-treated patients.

Contraindication

ADCETRIS concomitant with bleomycin due to pulmonary toxicity (e.g., interstitial infiltration and/or inflammation).

Warnings and Precautions

• Peripheral neuropathy (PN): ADCETRIS causes PN that is predominantly sensory. Cases of motor PN have also been reported. ADCETRIS-induced PN is cumulative. Monitor for symptoms such as hypoesthesia, hyperesthesia, paresthesia, discomfort, a burning sensation, neuropathic pain, or weakness. Institute dose modifications accordingly.
• Anaphylaxis and infusion reactions: Infusion-related reactions (IRR), including anaphylaxis, have occurred with ADCETRIS. Monitor patients during infusion. If an IRR occurs, interrupt the infusion and institute appropriate medical management. If anaphylaxis occurs, immediately and permanently discontinue the infusion and administer appropriate medical therapy. Premedicate patients with a prior IRR before subsequent infusions. Premedication may include acetaminophen, an antihistamine, and a corticosteroid.
• Hematologic toxicities: Fatal and serious cases of febrile neutropenia have been reported with ADCETRIS. Prolonged (≥1 week) severe neutropenia and Grade 3 or 4 thrombocytopenia or anemia can occur with ADCETRIS. Administer G-CSF primary prophylaxis starting with Cycle 1 for previously untreated patients who receive ADCETRIS in combination with chemotherapy for Stage III or IV classical HL. Monitor complete blood counts prior to each ADCETRIS dose. Consider more frequent monitoring for patients with Grade 3 or 4 neutropenia. Monitor patients for fever. If Grade 3 or 4 neutropenia develops, consider dose delays, reductions, discontinuation, or G-CSF prophylaxis with subsequent doses.
• Serious infections and opportunistic infections: Infections such as pneumonia, bacteremia, and sepsis or septic shock (including fatal outcomes) have been reported in ADCETRIS-treated patients. Closely monitor patients during treatment for bacterial, fungal, or viral infections.
• Tumor lysis syndrome: Closely monitor patients with rapidly proliferating tumor and high tumor burden.
• Increased toxicity in the presence of severe renal impairment: The frequency of ≥Grade 3 adverse reactions and deaths was greater in patients with severe renal impairment compared to patients with normal renal function. Avoid use in patients with severe renal impairment.
• Increased toxicity in the presence of moderate or severe hepatic impairment: The frequency of ≥Grade 3 adverse reactions and deaths was greater in patients with moderate or severe hepatic impairment compared to patients with normal hepatic function. Avoid use in patients with moderate or severe hepatic impairment.
• Hepatotoxicity: Fatal and serious cases have occurred in ADCETRIS-treated patients. Cases were consistent with hepatocellular injury, including elevations of transaminases and/or bilirubin, and occurred after the first ADCETRIS dose or rechallenge. Preexisting liver disease, elevated baseline liver enzymes, and concomitant medications may increase the risk. Monitor liver enzymes and bilirubin. Patients with new, worsening, or recurrent hepatotoxicity may require a delay, change in dose, or discontinuation of ADCETRIS.
• PML: Fatal cases of JC virus infection resulting in PML and death have been reported in ADCETRIS-treated patients. First onset of symptoms occurred at various times from initiation of ADCETRIS therapy, with some cases occurring within 3 months of initial exposure. Other possible contributory factors other than ADCETRIS include prior therapies and underlying disease that may cause immunosuppression. Consider PML diagnosis in patients with new-onset signs and symptoms of central nervous system abnormalities. Hold ADCETRIS if PML is suspected and discontinue ADCETRIS if PML is confirmed.
• Pulmonary toxicity: Fatal and serious events of noninfectious pulmonary toxicity including pneumonitis, interstitial lung disease, and acute respiratory distress syndrome have been reported. Monitor patients for signs and symptoms, including cough and dyspnea. In the event of new or worsening pulmonary symptoms, hold ADCETRIS dosing during evaluation and until symptomatic improvement.
• Serious dermatologic reactions: Fatal and serious cases of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have been reported with ADCETRIS. If SJS or TEN occurs, discontinue ADCETRIS and administer appropriate medical therapy.
• Gastrointestinal (GI) complications: Fatal and serious cases of acute pancreatitis have been reported. Other fatal and serious GI complications include perforation, hemorrhage, erosion, ulcer, intestinal obstruction, enterocolitis, neutropenic colitis, and ileus. Lymphoma with preexisting GI involvement may increase the risk of perforation. In the event of new or worsening GI symptoms, perform a prompt diagnostic evaluation and treat appropriately.
• Embryo-fetal toxicity: Based on the mechanism of action and animal studies, ADCETRIS can cause fetal harm. Advise females of reproductive potential of the potential risk to the fetus, and to avoid pregnancy during ADCETRIS treatment and for at least 6 months after the final dose of ADCETRIS.

Most Common (≥20%) Adverse Reactions: Neutropenia, anemia, peripheral sensory neuropathy, nausea, fatigue, constipation, diarrhea, vomiting, and pyrexia.

Drug Interactions

Concomitant use of strong CYP3A4 inhibitors or inducers, or P-gp inhibitors, has the potential to affect the exposure to monomethyl auristatin E (MMAE).

Use in Specific Populations

Moderate or severe hepatic impairment or severe renal impairment: MMAE exposure and adverse reactions are increased. Avoid use.

Advise males with female sexual partners of reproductive potential to use effective contraception during ADCETRIS treatment and for at least 6 months after the final dose of ADCETRIS.

Advise patients to report pregnancy immediately and avoid breastfeeding while receiving ADCETRIS.

For additional Important Safety Information, including BOXED WARNING, please see the full Prescribing Information for ADCETRIS at www.seattlegenetics.com or http://www.adcetris.com.

Forward Looking Statements

Certain of the statements made in this press release are forward looking, such as those, among others, relating to the potential utilization of ADCETRIS (brentuximab vedotin) for patients with previously untreated Stage III or IV classical Hodgkin lymphoma and other possible uses, and the evaluation of ADCETRIS as a foundation of therapy for Hodgkin lymphoma. Actual results or developments may differ materially from those projected or implied in these forward-looking statements due to factors such as utilization and adoption of the approved treatment regimen by prescribing physicians, competitive conditions including the availability of alternative treatment regimens, the availability and extent of reimbursement, the risk of adverse events, and adverse regulatory action. More information about the risks and uncertainties faced by Seattle Genetics is contained under the caption “Risk Factors” included in the company’s Quarterly Report on Form 10-Q for the quarter ended June 30, 2018 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.