Takeda and Pfizer Share Four-Year Data from Positive Phase 3 HD21 Trial of ADCETRIS® Combo in Frontline Hodgkin Lymphoma

The German Hodgkin Study Group (GHSG) has released promising findings from their Phase 3 HD21 trial, which evaluated the efficacy of ADCETRIS® (brentuximab vedotin) combined with chemotherapy in treating patients with newly diagnosed advanced classical Hodgkin lymphoma. This study compared the ADCETRIS combination regimen, known as BrECADD (brentuximab vedotin, etoposide, cyclophosphamide, doxorubicin, dacarbazine, and dexamethasone), against a currently utilized standard of care in Europe, known as eBEACOPP (escalated doses of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone).

The four-year analysis revealed that BrECADD improved progression-free survival (PFS) and demonstrated a better safety profile compared to eBEACOPP. The results of this study will be presented at significant medical conferences, including the 60th American Society of Clinical Oncology (ASCO) Annual Meeting and the 29th European Hematology Association (EHA) Annual Meeting.

The HD21 study, backed by Takeda and Pfizer, enrolled patients with newly diagnosed Stage IIb with large mediastinal mass and/or extranodal lesions, Stage III or IV Hodgkin lymphoma. Participants were randomized to receive either the BrECADD regimen or eBEACOPP, followed by interim PET staging to decide the continuation of treatment. The trial's primary endpoints were safety, assessed by treatment-related morbidity (TRMB), and efficacy, assessed by PFS.

At the preplanned three-year analysis, the study met its co-primary endpoints, showing that the BrECADD regimen significantly reduced treatment-related toxicities and maintained non-inferior PFS compared to eBEACOPP. The four-year data further highlighted that BrECADD achieved superior efficacy with a PFS of 94.3% compared to 90.9% for eBEACOPP, with a hazard ratio of 0.66, showcasing its advantage in prolonging the time patients lived without disease progression.

In addition to efficacy, the safety profile of ADCETRIS in the BrECADD regimen was consistent with other established ADCETRIS combination therapies, with no new safety concerns reported. The treatment was associated with fewer acute and long-lasting toxicities compared to eBEACOPP, thus presenting a favorable risk-benefit ratio for patients.

Dr. Peter Borchmann, the trial chairman from the University Hospital of Cologne, expressed optimism about the ADCETRIS combination, highlighting its potential to offer significant benefits to patients with advanced Hodgkin lymphoma. This sentiment was echoed by Awny Farajallah, chief medical officer of global oncology at Takeda, who emphasized the importance of this collaboration to enhance treatment outcomes and reduce side effects for patients.

The HD21 trial's findings contribute to the growing body of evidence supporting ADCETRIS as a crucial component in the treatment of specific lymphomas. Takeda will handle the regulatory submission for ADCETRIS based on the HD21 study findings outside the U.S. and Canada, while Pfizer retains the commercialization rights within these regions.

Overall, the results from the HD21 study underscore the potential of the ADCETRIS + ECADD regimen to become a new standard of care for patients with newly diagnosed advanced classical Hodgkin lymphoma, offering a treatment option that balances efficacy with reduced toxicity.