BOTHELL - 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.

About the HD21 Study

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

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