Phase III trial of Adcetris 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.-Seagen + Takeda

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. 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 III trial in advanced cHL and suggest that the BrECADD regimen may be the most effective therapy regimen currently available in advanced cHL.”

Results from the GHSG’s HD21 Trial : Among 1,482 patients at median follow up of 40 months, an intent-to-treat analysis showed: i. 3-year PFS was 94.9% for BrECADD vs. 92.3% for eBEACOPP (HR=0.63 [99% CI: 0.37, 1.07]). ii. 1-year PFS was 97.5% for BrECADD (99% CI: 96, 99). iii. 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 greater than 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.