On November 2, 2023 Seagen Inc. (NASDAQ: SGEN) reported that 12- and 24-month progression free survival data will be presented for an ADCETRIS (brentuximab vedotin) and immunotherapy combination in early and advanced stage classical Hodgkin lymphoma (cHL), respectively (Press release, Seagen, NOV 2, 2023, View Source [SID1234636793]). The data will be featured in two oral presentations at the 65th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting & Exposition, taking place December 9-12, 2023 in San Diego. The ongoing Phase 2 clinical trial, SGN35-027, is evaluating ADCETRIS in combination with immunotherapy and chemotherapy.
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In addition, pre-clinical data will be presented for a next-generation novel CD30-directed antibody-drug conjugate (ADC), SGN-35C, that uses a topoisomerase I inhibitor payload.
"These new data highlight our continued research and development focus on novel combinations to treat Hodgkin lymphoma and on next-generation CD30-directed therapies that aim to further improve outcomes while reducing treatment burden for patients," said Roger Dansey, M.D., President, Research and Development and Chief Medical Officer at Seagen.
ADCETRIS is a proven foundation of care for certain CD30-expressing lymphomas with more than 120,000 patients treated globally across seven indications.
Key data for Seagen at ASH (Free ASH Whitepaper) include:
Presentations of Company-Sponsored Trials
Abstract Title
Abstract #
Presentation
Lead Author
Brentuximab vedotin
Brentuximab vedotin, nivolumab, doxorubicin, and dacarbazine for advanced stage classical Hodgkin lymphoma: efficacy and safety results from the single arm phase 2 study (SGN35-027 Part B)
608
Oral 624
Sunday, Dec. 10
4:45 p.m. PT
Grand Hall B
Lee
Brentuximab vedotin, nivolumab, doxorubicin, and dacarbazine (AN+AD) for early-stage classical Hodgkin lymphoma (SGN35-027 Part C)
611
Oral 624
Sunday, Dec. 10
5:30 p.m. PT
Grand Hall B
Abramson
Brentuximab vedotin in frontline therapy of Hodgkin lymphoma in patients with significant comorbidities ineligible for standard chemotherapy (SGN35-015 Part E)
4435
Poster
Monday, Dec. 11
6:00 – 8:00 p.m. PT
Halls G-H
Yasenchak
PET4 response as an independent predictor of long-term outcomes in ECHELON-2 A+CHP vs CHOP in CD30+PTCL
3074
Poster
Sunday, Dec. 10
6:00 – 8:00 p.m. PT
Halls G-H
Iyer
The comparative effectiveness of A+AVD vs PET-guided ABVD for the management of patients with advanced Hodgkin lymphoma: a systematic review and matching-adjusted indirect treatment comparison (Takeda sponsored)
1713
Poster
Saturday, Dec. 9
5:30 – 7:30 p.m. PT
Halls G-H
Kristo
Real-world treatment patterns and patient outcomes in relapsed/refractory Hodgkin lymphoma in the US (Takeda sponsored)
–
Abstract only
Kristo
Early-Stage/Pipeline
SGN-35C: a novel CD30-directed antibody-drug conjugate for the treatment of lymphomas
1440
Poster
Saturday, Dec. 9
5:30 – 7:30 p.m. PT
Halls G-H
Hamblett
Presentations of Investigator and Cooperative Group-Sponsored Trials
Abstract Title
Abstract #
Presentation
Lead Author
Brentuximab vedotin
Identifying tumor-specific immune response and biomarkers of high-risk Hodgkin lymphoma patients treated with and without brentuximab on Children’s Oncology Group trial AHOD1331
4383
Poster, Monday, Dec. 11
6:00 – 8:00 p.m. PT
Halls G-H
Toner
Longitudinal differences by treatment arm in health-related quality of life among high risk pediatric Hodgkin’s lymphoma patients treated on the Children’s Oncology Group AHOD 1331 study
672
Oral 905
Sunday, Dec. 10
5:54 p.m. PT
Grand Ballroom 2-4
Williams
AHOD2131: a randomized phase 3 response-adapted trial comparing standard therapy with immuno-oncology therapy for children and adults with newly diagnosed stage I and II classic Hodgkin lymphoma
3084
Poster
Sunday, Dec. 10
6:00 – 8:00 p.m. PT
Halls G-H
Henderson
Brentuximab vedotin in combination with nivolumab in CD30+ malignancies refractory to brentuximab vedotin
3060
Poster
Sunday, Dec. 10
6:00 – 8:00 p.m. PT
Halls G-H
Poh
Reduced dose brentuximab vedotin for mycosis fungoides appears to prolong response duration by balancing efficacy and tolerability
1702
Poster Saturday, Dec. 9
5:30 – 7:30 p.m. PT
Halls G-H
Munayirji
Final results of a multicenter pilot study evaluating brentuximab vedotin with cyclophosphamide, doxorubicin, etoposide, and prednisone (BV-CHEP) for the treatment of aggressive adult T-cell leukemia/lymphoma
1692
Poster
Saturday, Dec. 9
5:30 – 7:30 p.m. PT
Halls G-H
Dittus
Immune landscape associated with response to brentuximab vedotin with ipilimumab and/or nivolumab in relapsed/refractory Hodgkin lymphoma (E4412 phase 1)
4382
Poster
Monday, Dec. 11
6:00 – 8:00 p.m. PT
Halls G-H
Gonzalez-Kozlova
CNS involvement in pediatric Hodgkin lymphoma: a comprehensive retrospective analysis from the SEARCH for CAYAHL group
3066
Poster
Sunday, Dec. 10
6:00 – 8:00 p.m. PT
Halls G-H
Pabari
Comprehensive analysis of treatment related morbidity and progression-free survival in the GHSG phase III HD21 trial
3057
Poster
Sunday, Dec. 10
6:00 – 8:00 p.m. PT
Halls G-H
Borchmann
Pregnancies and childbirth following advanced-stage HL treatment with BrECADD or BEACOPP in the randomized phase III GHSG HD21 trial
4437
Poster
Monday, Dec. 11 6:00-8:00 p.m.
Halls G-H
Ferdinandus
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 in seven indications in the U.S.:
Adult patients with previously untreated Stage III/IV cHL in combination with doxorubicin, vinblastine, and dacarbazine (2018)
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 cHL at high risk of relapse or progression as post-autologous hematopoietic stem cell transplantation (auto-HSCT) consolidation (2015)
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)
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 sALCL after failure of at least one prior multi-agent chemotherapy regimen (2011)
Adult patients with primary cutaneous anaplastic large cell lymphoma (pcALCL) or CD30-expressing mycosis fungoides (MF) after prior systemic therapy (2017)
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.