Phase 3 Trial of ADCETRIS® (brentuximab vedotin) with Modified Chemo Regimen Shows Non-Inferiority with Unprecedented 3-Year Progression Free Survival of 94.9% vs Less Tolerable International Standard of Care in Advanced Classical Hodgkin Lymphoma
- Category: Antibodies
- Published on Wednesday, 21 June 2023 09:57
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– Results are from 1,500 patient trial conducted by German Hodgkin Study Group to test ADCETRIS regimen versus international standard eBEACOPP therapy
– ADCETRIS regimen showed less peripheral neuropathy
BOTHELL, WA, USA I June 20, 2023 I Seagen Inc. (NASDAQ: SGEN) today announced that the clinical research cooperative German Hodgkin Study Group (GHSG) presented results showing that a phase 3 trial of ADCETRIS® in combination with chemotherapy – a regimen called BrECADD (brentuximab vedotin [ADCETRIS], etoposide, cyclophosphamide, doxorubicin [Adriamycin], dacarbazine, and dexamethasone) – met its co-primary endpoints of non-inferior efficacy and superior tolerability versus a highly efficacious yet chemotherapy-intense treatment regimen of escalated BEACOPP (bleomycin, etoposide, doxorubicin (Adriamycin), cyclophosphamide, vincristine, procarbazine, and prednisone), which is an international standard of care in the frontline advanced classical Hodgkin lymphoma (cHL) setting and commonly used in Europe. Both study arms used PET scans to guide treatment decisions. The data results of the HD21 study were presented in a late-breaking session at the 17th International Conference on Malignant Lymphoma (ICML) in Lugano, Switzerland on June 17.
An interim analysis at 40 months showed an unprecedented 94.9% 3-year progression-free survival (PFS) (99% CI: 92.8, 97.1) for patients treated with the ADCETRIS combination of BrECADD versus 92.3% for eBEACOPP (99% CI: 89.7, 94.9). 12-month post-treatment safety data were consistent with previously presented HD21 data results at the American Society of Hematology 2022 Annual Meeting.
ADCETRIS + AVD chemotherapy (Adriamycin, vinblastine, dacarbazine) is a U.S. standard of care in advanced-stage cHL and is the only targeted therapy inclusive regimen that has a proven statistically significant overall survival benefit at 6-years of follow-up compared to ABVD, reducing risk of death by 41% for these patients.i,ii ADCETRIS is approved for seven indications in the U.S. and six indications in Europe, where Takeda has commercialization rights.
“Our mission in Hodgkin lymphoma is to cure patients with a first-line treatment that reduces the risk of cancer returning as much as possible so patients can go on with their lives,” said Professor Dr. med. Peter Borchmann, Assistant Medical Director, Department of Hematology and Oncology at the University Hospital of Cologne, Germany and Head of the Lymphoma Program, Head of the German Hodgkin Study Group and Trial Chairman of the HD21 study. “The mature results of this study demonstrate 3-year efficacy never previously observed in a phase 3 trial in advanced cHL and suggest that the BrECADD regimen may be the most effective therapy regimen currently available in advanced cHL.”
“We are enthusiastic about these strong and durable efficacy outcomes and tolerability findings of an ADCETRIS based chemotherapy regimen compared to an international standard chemotherapy. We are evaluating these results to determine next steps,” said Roger Dansey, President of Research and Development and Chief Medical Officer at Seagen.
Results from the GHSG’s HD21 Trial
Among 1,482 patients at median follow up of 40 months, an intent-to-treat analysis showed:
- 3-year PFS was 94.9% for BrECADD vs. 92.3% for eBEACOPP (HR=0.63 [99% CI: 0.37, 1.07])
- 1-year PFS was 97.5% for BrECADD (99% CI: 96, 99)
- 3-year overall survival was 98.5% in both treatment arms
12-month post-treatment safety information was available for 95 percent of patients (n=1,395), which showed the rate of grade ≥2 peripheral neuropathy was lower with BrECADD (1.9%) vs. eBEACOPP (2.7%) with most patients having no or low (grade 1) peripheral neuropathy (98.1% for BrECADD vs. 97.3% for eBEACOPP).
Preservation of fertility potential was indicated by measurement of follicle-stimulating hormone (FSH) and was available for 597 patients. Preservation of fertility potential was numerically favorable for the BrECADD arm vs. eBEACOPP. Mean FSH levels were 29.4 and 31.8 after 4 and 6 cycles, respectively for eBEACOPP, and 18.3 and 20.5 after 4 and 6 cycles, respectively, for BrECADD. Persistently elevated FSH is associated with impaired gonadal function. Additional analysis is required to understand the significance of these findings.
Please see Important Safety Information, including a BOXED WARNING for progressive multifocal leukoencephalopathy (PML), for ADCETRIS below.
The GHSG’s phase 3 HD21 trial in advanced cHL enrolled 1,500 patients from 9 countries between July 2016 and August 2020. The median age was 34 years old (range 18-61), and 47 percent were considered high-risk with an international prognostic index ≥3. 59% of patients received four cycles of therapy and 41% received six cycles of therapy. Patients were randomized in a 1:1 ratio to PET2-guided 4-6 cycles of either BrECADD or eBEACOPP. PET2 and PFS events were assessed by blinded panel review. Non-inferiority of the primary efficacy endpoint PFS was defined as absolute difference <6% at five years corresponding to an HR of BrECADD vs eBEACOPP <1.69. The study was funded by Takeda.
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.iii 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.iv
About The German Hodgkin Study Group
For over 30 years, the German Hodgkin Study Group (GHSG) has been committed to optimizing diagnostics, therapy and follow-up care in Hodgkin lymphoma. The GHSG’s Trial Coordination Center belongs to the Department of Internal Medicine at the University of Cologne. It recruits patients from across Europe, and over 15,000 patients have participated in its clinical trials. With the results of its large-scale controlled, prospective and randomized trials for all stages of Hodgkin lymphoma, the GHSG has contributed decisively to the great progress in Hodgkin lymphoma therapy over the years. The GHSG’s latest trials aim to reduce adverse effects of therapy while maintaining cure rates.
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. ADCETRIS received conditional marketing authorization from the European Commission in October 2012. Its approved indications in Europe are for:
- Adult patients with previously untreated CD30-positive Stage IV Hodgkin lymphoma in combination with AVD
- Adult patients with CD30-positive Hodgkin lymphoma at increased risk of relapse or progression following ASCT.
- 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.
- Adult patients with relapsed or refractory sALCL
- Adult patients with previously untreated sALCL in combination with CHP
- Adult patients with CD30-positive cutaneous T-cell lymphoma (CTCL) after at least one prior systemic therapy
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.
Please see the full Prescribing Information, including BOXED WARNING, for ADCETRIS here.
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 Twitter and LinkedIn.