ADCETRIS® (brentuximab vedotin) Plus Standard of Care Chemotherapy Demonstrates Superior Event-Free Survival (EFS) vs. Standard of Care Alone in Children and Young Adults with Previously Untreated High-Risk Hodgkin Lymphoma

– Children’s Oncology Group (COG) to Present Data from Investigator-sponsored Study at 59th American Society of Clinical Oncology (ASCO) Annual Meeting –

– Phase 3 Clinical Trial of ADCETRIS Combination Therapy Demonstrated a 59% Reduction in Risk of Disease Progression or Relapse, Second Malignancy or Death vs. Standard of Care –

– Data Supported Seagen’s Recent Supplemental Biologics License Application (sBLA) to FDA Seeking Label Expansion in Children and Young Adults –

BOTHELL, Wash.--(BUSINESS WIRE)--Seagen Inc. (Nasdaq: SGEN) today announced results from a presentation by the Children's Oncology Group (COG) of a phase 3 trial (AHOD1331) evaluating ADCETRIS^® (brentuximab vedotin) in children and young adults with high-risk, previously untreated classical Hodgkin lymphoma (cHL). The trial showed ADCETRIS in combination with standard of care dose-intensive chemotherapy AVE-PC [Adriamycin (doxorubicin), vincristine, etoposide, prednisone and cyclophosphamide] achieved superior event-free survival (EFS) compared to the current standard of care for the pediatric dose-intensive regimen of ABVE-PC [Adriamycin (doxorubicin), bleomycin, vincristine, etoposide, prednisone and cyclophosphamide], as part of the multi-modality treatment. The findings were presented by COG in an oral session at the 59th American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago on Friday, June 3, 2022, 1-4 p.m. CT.

In the study, 600 pediatric and young adult patients were randomized to either the experimental brentuximab vedotin plus AVE-PC (BV-AVE-PC) arm or the standard chemotherapy ABVE-PC arm. Results from the BV-AVE-PC arm showed a clinically meaningful and statistically significant 59% reduction in the risk of disease progression or relapse, second malignancy or death [Hazard Ratio (HR) 0.41; p=0.0002]. At median follow-up of 42.1 months, 3-year EFS rate in the BV-AVE-PC arm was 92.1% compared to 82.5% in the control arm.

ADCETRIS in combination with AVE-PC was well tolerated with a manageable safety profile in pediatric patients. Grade 3+ adverse events recorded, including febrile neutropenia, were comparable across both arms and consistent with the known dose-intensive chemotherapy regimen. Grade 2+ peripheral neuropathy rates were similar across both arms. No deaths occurred during treatment.

Please see Important Safety Information, including BOXED WARNING, for ADCETRIS, below.

“Brentuximab vedotin is an established medicine for the treatment of adults with classical Hodgkin lymphoma. We are excited about these new event-free survival data in previously untreated, high-risk children and adolescents and what it could mean for our younger patient,” said Sharon M. Castellino, M.D., M.Sc., Professor, Department of Pediatrics, Emory University School of Medicine, AHOD1331 Study Chair and COG Hodgkin Lymphoma Disease Committee Chair.

“We are delighted to see the positive results of this ADCETRIS trial in pediatric patients, and we thank the Children’s Oncology Group for their work to advance the treatment of classical Hodgkin lymphoma,” said Marjorie Green, M.D., Senior Vice President, Late-Stage Development at Seagen. “These data supported the submission of a supplemental Biologics License Application for ADCETRIS to potentially expand its indication to include children and adolescents with high-risk, previously untreated classical Hodgkin lymphoma.”

About the Children's Oncology Group AHOD1331 Phase 3 Study

This National Cancer Institute (NCI)-sponsored study was conducted by the Children’s Oncology Group (COG), which is funded by NCI, and is a multicenter, randomized, open-label phase 3 study enrolling 600 patients across 151 institutions from March 2015 to August 2019, from 2 to 21 years of age who had previously untreated Hodgkin lymphoma (HL), stages IIB + bulk, IIIB, IVA and IVB. Patient demographics and disease characteristics were balanced across study arms. Patients were randomized to five cycles of either standard of care dose-intensive chemotherapy (Adriamycin (doxorubicin), bleomycin. vincristine, etoposide, prednisone and cyclophosphamide [ABVE-PC]) or brentuximab vedotin plus AVE-PC (BV-AVE-PC) given every 21 days with granulocyte colony-stimulating factor support. The primary objective was event-free survival (EFS); events included relapse/progression, second malignant neoplasm (SMN) or death. Seagen provided brentuximab vedotin to the IND sponsor, NCI, part of the National Institutes of Health, under a Cooperative Research and Development Agreement (CRADA).

COG (childrensoncologygroup.org), a member of the NCI National Clinical Trials Network (NCTN), is the world’s largest organization devoted exclusively to childhood and adolescent cancer research. COG unites over 10,000 experts in childhood cancer at more than 200 leading children’s hospitals, universities and cancer centers across North America, Australia and New Zealand in the fight against childhood cancer. Today, more than 90% of the 16,000 children and adolescents diagnosed with cancer each year in the United States are cared for at COG member institutions. Research performed by COG institutions over the past 50 years has transformed childhood cancer from a virtually incurable disease to one with a combined five-year survival rate of 80%. COG’s mission is to improve the cure rate and outcomes for all children with cancer.

About Classical Hodgkin Lymphoma (cHL)

cHL is a cancer of the blood. It starts when lymphocytes, a type of white blood cell, grow out of control. People with cHL have abnormal white blood cells called Reed-Sternberg cells in their lymph nodes. These cells usually have a special protein on their surface called CD30, which is a key marker of cHL. CD30 is present in approximately 95% of all cases of Hodgkin lymphoma (HL). In 2022, the American Cancer Society estimates that there will be about 8,540 new cases of HL and an estimated 920 people will die of this disease in the U.S.¹

cHL has a bimodal age incidence that peaks in adolescents and young adults between the ages of 15 and 30 years and then again in adults aged 55 years or older². cHL represents about 6% of all childhood cancers.³

About ADCETRIS

ADCETRIS is an antibody-drug conjugate (ADC) comprising an anti-CD30 monoclonal antibody attached by a protease-cleavable linker to a microtubule disrupting agent, monomethyl auristatin E (MMAE), utilizing Seagen’s 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 cells.

ADCETRIS is indicated for the treatment of adult patients with:

• previously untreated Stage III or IV classical Hodgkin lymphoma (cHL), in combination with doxorubicin, vinblastine, and dacarbazine,
• cHL at high risk of relapse or progression as post-autologous hematopoietic stem cell transplantation (auto-HSCT) consolidation,
• 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,
• previously untreated systemic anaplastic large cell lymphoma (sALCL) or other CD30-expressing peripheral T-cell lymphomas (PTCL), including angioimmunoblastic T-cell lymphoma and PTCL not otherwise specified, in combination with cyclophosphamide, doxorubicin, and prednisone,
• sALCL after failure of at least one prior multi-agent chemotherapy regimen, and
• primary cutaneous anaplastic large cell lymphoma (pcALCL) or CD30-expressing mycosis fungoides who have received prior systemic therapy.

Seagen and Takeda are jointly developing ADCETRIS. Under the terms of the collaboration agreement, Seagen has U.S. and Canadian commercialization rights, and Takeda has rights to commercialize ADCETRIS in the rest of the world. Seagen 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.

ADCETRIS (brentuximab vedotin) for injection U.S. 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 beginning with Cycle 1 for patients who receive ADCETRIS in combination with chemotherapy for previously untreated Stage III/IV cHL or previously untreated PTCL.
  
  Monitor complete blood counts prior to each ADCETRIS dose. Monitor more frequently 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 have been reported in ADCETRIS-treated patients. First onset of symptoms occurred at various times from initiation of ADCETRIS, with some cases occurring within 3 months of initial exposure. In addition to ADCETRIS therapy, other possible contributory factors 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, including severe abdominal pain, perform a prompt diagnostic evaluation and treat appropriately.

• Hyperglycemia: Serious cases, such as new-onset hyperglycemia, exacerbation of pre-existing diabetes mellitus, and ketoacidosis (including fatal outcomes) have been reported with ADCETRIS. Hyperglycemia occurred more frequently in patients with high body mass index or diabetes. Monitor serum glucose and if hyperglycemia develops, administer anti-hyperglycemic medications as clinically indicated.

• 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% in any study) Adverse Reactions

Peripheral neuropathy, fatigue, nausea, diarrhea, neutropenia, upper respiratory tract infection, pyrexia, constipation, vomiting, alopecia, decreased weight, abdominal pain, anemia, stomatitis, lymphopenia, and mucositis.

Drug Interactions

Concomitant use of strong CYP3A4 inhibitors or inducers 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.

Please see the full Prescribing Information, including BOXED WARNING, for ADCETRIS here.

About Seagen

Seagen Inc. is a global biotechnology company that discovers, develops and commercializes transformative cancer medicines to make a meaningful difference in people’s lives. Seagen is headquartered in the Seattle, Washington area, and has locations in California, Canada, Switzerland and the European Union. For more information on our marketed products and robust pipeline, visit www.seagen.com and follow @SeagenGlobal on Twitter.

Forward-Looking Statements

Certain statements made in this press release are forward looking, such as those, among others, relating to the therapeutic potential of ADCETRIS, its possible safety, efficacy and therapeutic uses, submission of a supplemental Biologics License Application to potentially expand ADCETRIS’ label, plans to present results at an upcoming medical meeting, and anticipated and ongoing clinical development activities for ADCETRIS. 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 without limitation the possibility that the ADCETRIS may not receive any label expansion based on the results of the referenced clinical trial or otherwise, the risk of adverse events or safety signals, the possibility of adverse regulatory actions, and the potential for delays or setbacks in product development and the regulatory review process. More information about the risks and uncertainties faced by Seagen is contained under the caption “Risk Factors” included in Seagen’s Quarterly Report on Form 10-Q for the quarter ended March 31, 2022, and subsequent periodic reports, filed with the Securities and Exchange Commission. Seagen disclaims any intention or obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise except as required by applicable law.

¹ https://www.cancer.org/cancer/hodgkin-lymphoma.html
² https://onlinelibrary.wiley.com/doi/full/10.1002/ajh.25856
³ https://www.nfcr.org/cancer-types/childhood-cancer/

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