ADCETRIS® (brentuximab vedotin) Plus Novel Immunotherapy Combination Delivers 100% Progression Free Survival at 12 months in Phase 2 Trial of Patients with Early Stage Classical Hodgkin Lymphoma

– 88% of patients with advanced stage classical Hodgkin Lymphoma in trial remained progression free at 24 months –

– Investigational regimen that eliminates two commonly used chemotherapy agents, vinblastine and bleomycin, continues to show consistent safety and tolerability profile, with no cases of febrile neutropenia and no new safety signals observed –

BOTHELL, Wash.--(BUSINESS WIRE)--#ASH23--Seagen Inc. (NASDAQ: SGEN) today announced that clinically meaningful progression-free survival (PFS), a secondary endpoint, was observed in a Phase 2 study evaluating the antibody-drug conjugate (ADC) ADCETRIS^® (brentuximab vedotin) in combination with the PD-1 inhibitor nivolumab and standard chemotherapy agents doxorubicin and dacarbazine (AN+AD) as first-line treatment for early and advanced stage classical Hodgkin lymphoma (cHL). This is the first time 12-month PFS results were presented for the treatment combination, which avoids use of vinblastine and bleomycin in patients with early stage cHL. Results from the trial, called SGN35-027, were presented in an oral session at the 65^th American Society of Hematology Annual Meeting & Exposition in San Diego.

“Hodgkin lymphoma commonly strikes young adults, and our goal is to achieve the highest cure rate possible while reducing treatment and toxicity burden,” said Jeremy Abramson, M.D., Director, Jon and Jo Ann Hagler Center for Lymphoma at Massachusetts General Hospital, and principal investigator of the part of the trial that evaluated patients with early stage cHL. “These data show encouraging activity and safety for combining an ADC and immunotherapy, two medicines that have distinct and complementary mechanisms of action, allowing reduced reliance on traditional cytotoxic chemotherapies.”

“These data continue to demonstrate favorable clinical outcomes of an ADCETRIS plus nivolumab immunotherapy combination that reduces chemotherapy treatment burden and warrant further study,” said Roger Dansey, M.D., President, Research and Development and Chief Medical Officer at Seagen.

Oral #611: Brentuximab vedotin, nivolumab, doxorubicin, and dacarbazine (AN+AD) for early-stage classical Hodgkin lymphoma: Updated results reporting progression-free survival in an ongoing Phase 2 study (SGN35-027 Part C)

SGN35-027 Part C is investigating the novel ADCETRIS combination in 154 patients with early stage (non-bulky Stage I or II) cHL.

• Among 150 efficacy-evaluable patients, 98% had an overall response (OR) (95% CI: 94.3, 99.6) and 93% had a complete response (CR) (95% CI:88.1, 96.8) at the end of treatment.
• 99% of patients who responded (95% CI: 95.0, 99.9) had a duration of response (DOR) beyond 12 months; 98% of patients who had a complete response (95% CI: 93.7, 99.6) had a duration of CR (DOCR) beyond 12 months.
• The PFS rate was 100% (95% CI: 100, 100) at 12 months and 97% (95% CI: 90.3, 99.1) at 18 months.
• The most frequently reported treatment-emergent adverse events (TEAEs) Grade 3 or higher were neutropenia (9%), increased alanine aminotransferase (7%), and increased aspartate aminotransferase (5%).
• Peripheral sensory neuropathy was primarily low grade (3% Grade ≥3).
• There were no cases of febrile neutropenia and no deaths.
• Treatment-emergent immune-mediated adverse events (IMAEs) were primarily low-grade and consistent with the individual safety profile of nivolumab.

Oral #608: Brentuximab vedotin, nivolumab, doxorubicin, and dacarbazine for advanced stage classical Hodgkin lymphoma: Updated efficacy and safety results from the single arm Phase 2 study (SGN35-027 Part B)

SGN35-027 Part B is investigating the novel ADCETRIS combination in 57 patients with advanced-stage cHL (Stage II with bulky disease, Stage III or IV).

• Among 56 efficacy-evaluable patients, 95% had an OR (95% CI: 85.1, 98.9) and 89% had a CR (95% CI: 78.1, 96.0).
• 88% of patients who responded (95% CI: 75.7, 94.6) had a DOR beyond 24 months; 88% of patients who had a CR (95% CI: 76.0, 94.6) had a DOCR beyond 24 months.
• The estimated PFS rate at 24 months was 88% (95% CI: 75.7, 94.6), with a median follow-up of 24.2 months (95% CI: 23.4, 26.9).
• The most frequently reported TEAEs Grade 3 or higher were increased alanine aminotransferase (11%) and neutropenia (9%).
• Peripheral sensory neuropathy was primarily low grade (4% Grade ≥3).
• No febrile neutropenia and no deaths were reported.
• IMAEs were primarily low-grade and consistent with the individual safety profile of nivolumab. No subsequent radiation therapy was given to patients.

ADCETRIS is a proven foundation of care for CD30-expressing lymphomas with more than 120,000 patients treated globally across seven indications. In combination with Adriamycin, vinblastine and dacarbazine (AVD) chemotherapy, ADCETRIS is the first medicine to include overall survival data in its Prescribing Information for previously untreated Stage III/IV cHL.¹

Please see Important Safety Information, including a BOXED WARNING for progressive multifocal leukoencephalopathy (PML), for ADCETRIS below.

About SGN35-027

SGN35-027 is an ongoing open-label, multiple part, multicenter, single-arm Phase 2 clinical trial evaluating brentuximab vedotin treatment combinations in patients with early- and advanced-stage cHL. Parts B and C of the trial are investigating brentuximab vedotin in combination with the PD-1 inhibitor nivolumab and chemotherapy agents doxorubicin and dacarbazine. Part B is evaluating the combination in patients with stage II bulky (mediastinal mass ≥10 cm), Stage III or IV cHL. Part C is evaluating the combination in patients with Stage I or II cHL without bulky mediastinal disease (<10 cm). The primary endpoint for Parts B and C is the proportion of participants with complete response at end of treatment according to the Lymphoma Response to Immunomodulatory Therapy Criteria (LYRIC).

About Hodgkin Lymphoma

Lymphoma is a general term for a group of cancers that originate in the lymphatic system affecting a type of white blood cell called lymphocytes. There are two major categories of lymphoma: Hodgkin lymphoma and non-Hodgkin lymphoma. Hodgkin lymphoma is distinguished by the presence of Reed-Sternberg cells that usually have a protein called CD30 on their surface. Approximately 8,830 cases of classical Hodgkin lymphoma will be diagnosed in the United States during 2023 and 900 people will die from the disease.² According to the International Agency for Research on Cancer in 2020, over 83,000 people worldwide were diagnosed with Hodgkin lymphoma and approximately 23,000 people died from this cancer.³

About ADCETRIS

ADCETRIS is an antibody-drug conjugate (ADC) comprised of a CD30-directed 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-positive tumor cells.

ADCETRIS is approved for seven indications in the U.S.:

• Pediatric patients 2 years and older with previously untreated high risk cHL in combination with doxorubicin, vincristine, etoposide, prednisone and cyclophosphamide (2022)
• Adult patients with previously untreated Stage III/IV cHL in combination with doxorubicin, vinblastine, and dacarbazine (2018)
• Adult patients with 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 (2018)
• Adult patients with primary cutaneous anaplastic large cell lymphoma (pcALCL) or CD30-expressing mycosis fungoides (MF) after prior systemic therapy (2017) Adult patients with cHL at high risk of relapse or progression as post-autologous hematopoietic stem cell transplantation (auto-HSCT) consolidation (2015)
• Adult patients with sALCL after failure of at least one prior multi-agent chemotherapy regimen. (2011)
• Adult patients with cHL after failure of auto-HSCT or after failure of at least two prior multi-agent chemotherapy regimens in patients who are not auto-HSCT candidates (2011)

ADCETRIS has marketing authorization in more than 70 countries for relapsed or refractory Hodgkin lymphoma and systemic anaplastic large cell lymphoma.

Seagen and Takeda jointly develop 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

Contraindicated with concomitant 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. Patients experiencing new or worsening PN may require a delay, change in dose, or discontinuation of ADCETRIS.

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 adult patients who receive ADCETRIS in combination with chemotherapy for previously untreated Stage III/IV cHL or previously untreated PTCL, and pediatric patients who receive ADCETRIS in combination with chemotherapy for previously untreated high risk cHL.

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 infections.

Tumor lysis syndrome: Patients with rapidly proliferating tumor and high tumor burden may be at increased risk. Monitor closely and take appropriate measures.

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. 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. 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 preexisting 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 this potential risk, and to use effective contraception during ADCETRIS treatment and for 2 months after the last dose of ADCETRIS. Advise male patients with female partners of reproductive potential to use effective contraception during ADCETRIS treatment and for 4 months after the last dose of ADCETRIS.

ADVERSE REACTIONS

The most common adverse reactions (≥20% in any study) are peripheral neuropathy, fatigue, nausea, diarrhea, neutropenia, upper respiratory tract infection, pyrexia, constipation, vomiting, alopecia, decreased weight, abdominal pain, anemia, stomatitis, lymphopenia, mucositis, thrombocytopenia, and febrile neutropenia.

DRUG INTERACTIONS

Concomitant use of strong CYP3A4 inhibitors has the potential to affect the exposure to monomethyl auristatin E (MMAE). Closely monitor adverse reactions.

USE IN SPECIAL POPULATIONS

Lactation: Breastfeeding is not recommended during ADCETRIS treatment.

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

About Seagen

Founded 25 years ago, Seagen Inc. is a global biotechnology company that discovers, develops, manufactures and commercializes targeted cancer therapeutics, with antibody-drug conjugates (ADCs) at our core. Our colleagues work together with urgency to improve and extend the lives of people living with cancer. An ADC technology trailblazer, approximately one-third of FDA-approved and marketed ADCs use Seagen technology. Seagen is headquartered in Bothell, Washington and has locations in California, Canada, Switzerland and across Europe. For additional information, visit seagen.com and follow us on X and LinkedIn.

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, alone or in combination; its safety, efficacy and therapeutic uses; and planned and ongoing clinical trials. 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 risk of delays, setbacks or failures in product development activities, even after encouraging results in earlier-stage trials, for a variety of reasons, including without limitation the difficulty and uncertainty of pharmaceutical product development, the possibility that clinical results may not support continued development or regulatory approvals, the risk of adverse events or safety signals, and the possibility of adverse regulatory actions. 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 September 30, 2023, and Seagen’s subsequent 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 ADCETRIS [package insert]. Bothell, WA: Seagen Inc.
2 American Cancer Society. Key Statistics for Hodgkin Lymphoma. https://www.cancer.org/cancer/hodgkin-lymphoma/about/key-statistics.html. Accessed November 2023.
² International Agency for Research on Cancer. Hodgkin Lymphoma. https://gco.iarc.fr/today/data/factsheets/cancers/33-Hodgkin-lymphoma-fact-sheet.pdf. Accessed November 2023.

For Media
David Caouette
(310) 430-3476
dcaouette@seagen.com

For Investors
Douglas Maffei, Ph.D.
(425) 527-4160
dmaffei@seagen.com