Seattle Genetics and Takeda Pharmaceutical announced the publication of long-term, final results from the pivotal Phase 2 clinical trial that led to the approval of Adcetris (brentuximab vedotin) as monotherapy in patients with relapsed or refractory classical Hodgkin’s lymphoma.
The article, “Five-year survival and durability results of brentuximab vedotin in patients with relapsed or refractory Hodgkin lymphoma,” published in the journal Blood, reports the five-year durability results and emphasizes that patients who reached complete response achieved long-term disease control. Patients in this study had previously failed to respond to hematopoietic autologous stem cell transplantation.
“At the time of trial initiation, historical outcomes for Hodgkin lymphoma patients who relapsed after an autologous stem cell transplant were poor, with median post-progression survival of 1.3 years, and the only long-term disease control option for these patients was considered to be an allogeneic stem cell transplant,” Robert Chen, MD, City of Hope National Medical Center in California and lead author of the Blood manuscript, said in a press release. “The median survival of the patients on ADCETRIS monotherapy in this pivotal Phase 2 trial exceeds these historic figures, and I am pleased to see the publication of the final data.”
Adcetris, an antibody-drug conjugate, binds to a molecule known as CD30 in Hodgkin’s lymphoma and anaplastic T-cell lymphoma cells. CD30 expression varies in subtypes of lymphoma, but it is estimated to be present in one-quarter to one-third of all B-cell non-Hodgkin’s lymphomas. This conjugate interferes with cell growth and division and, once inside the cancer cell, brentuximab separates from the antibody to begin to work. Adcetris is being examined as a foundation therapy for Hodgkin’s lymphoma in more than 45 ongoing clinical trials worldwide.
The open-label trial (NCT00848926) was conducted in 102 patients with relapsed/refractory Hodgkin lymphoma (HL), after failed hematopoietic autologous stem cell transplantation (auto-SCT). All patients had received a median of more than three prior chemotherapy regimens. The trial assessed Adcetris’ efficacy and safety as monotherapy.
Final trial results showed that:
- Median overall survival and progression-free survival in patients overall was 40.5 months and 9.3 months, respectively. The five-year estimated overall survival rate was 41% and progression-free survival rate was 22%.
- Of the total group treated, 34 patients (33%) achieved a complete response to treatment and had estimated five-year overall and progression-free survival rates of 64% and 52%, respectively.
- Thirteen of these 34 patients (38%) have remained in remission for over five years. Of these 13, four underwent consolidative allogeneic stem cell transplants while in remission, and nine received no further therapy.
- Adverse side effects of Adcetris treatment include fatigue, nausea, low white blood counts, diarrhea, and peripheral sensory neuropathy.
“Today’s final publication of the ADCETRIS monotherapy pivotal study in Hodgkin lymphoma patients represents a significant milestone for the trial that supported approval in more than 60 countries globally and established current use as standard-of-care in the relapsed setting,” said Jonathan Drachman, MD, chief medical officer and executive vice president, Research and Development, at Seattle Genetics. “The long-term safety and efficacy data from the pivotal trial are supportive of our ongoing development of ADCETRIS for other classical Hodgkin lymphoma settings, including the frontline setting.”
Adcetris was approved by the U.S. Food and Drug Administration (FDA) in 2011 to treat Hodgkin’s lymphoma in patients whose disease has progressed after autologous stem cell transplant, or after two prior chemotherapy treatments for those who cannot receive a transplant, and to treat systemic anaplastic large cell lymphoma (ALCL).