Final data of the pivotal phase II clinical trial of brentuximab vedotin monotherapy in relapsed or refractory classical Hodgkin lymphoma were published in the journal Blood.

The results summarise the five-year, end-of-study results, highlights that patients who attained a complete response achieved long-term disease control.

Brentuximab vedotin is an antibody-drug conjugate (ADC), marketed by Seattle Genetics Inc and Takeda Pharmaceutical Company Ltd as Adcetris.

It is an anti-CD30 monoclonal antibody attached by a protease-cleavable linker to a microtubule disrupting agent, monomethyl auristatin E (MMAE), and is designed to be stable in the bloodstream but to release MMAE upon internalization into CD30-expressing tumour cells. 

“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. 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,” said Robert Chen, M.D., City of Hope National Medical Center, Duarte, California, and lead author of the Blood manuscript. “The median survival of the patients in this pivotal phase II trial exceeds these historic figures, and I am pleased to see the publication of the final data.” 

“For over a decade, we have demonstrated our commitment to improve treatment outcomes in Hodgkin lymphoma through numerous clinical trials evaluating novel therapeutic approaches. Today’s final publication of the trial results 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, M.D., 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. Our broad clinical program is investigating it as a foundation of care for Hodgkin lymphoma and potentially other CD30-expressing malignancies.” 

“The positive final results from this trial demonstrated that of the patients who had a complete response, 38 percent achieved long-term disease control for the duration of the study,” said Dirk Huebner, M.D., Executive Medical Director, Oncology Therapeutic Area Unit, Takeda Pharmaceutical Company. “In addition, the median overall survival of 40.5 months and progression-free survival of 9.3 months observed across the trial further establish the role of CD30 in improving outcomes for patients with relapsed Hodgkin lymphoma.” 

The pivotal, single-arm trial, which supported the FDA approval in for this indication, was conducted in 102 relapsed or refractory classical Hodgkin lymphoma patients who had previously received an autologous stem cell transplant (ASCT) to assess the efficacy and safety of single-agent therapy.

Enrolled patients had received a median of more than three prior chemotherapy regimens.

After a five-year follow-up period, the final results from the pivotal trial include: 

•  The median overall survival and progression-free survival were 40.5 months (95% confidence interval [CI]: 28.7, 61.9) and 9.3 months (95% CI: 7.1, 12.2), respectively. The estimated five-year overall survival and progression-free survival rates were 41 percent and 22 percent. 
•  Of the 102 patients treated, 34 patients (33%) had a complete remission, with the median response duration not reached. For patients who had a complete remission, the estimated five-year overall survival rate was 64 percent (95% CI: 48, 80) and the estimated five-year progression-free survival rate was 52 percent (95% CI: 34, 69). 
•  Thirteen of the 34 patients (38%) who achieved a complete remission continued to be followed and remained in remission for over five years at study closure. Of these patients, four underwent consolidative allogeneic stem cell transplants while in remission, and nine received no further therapy. 
•  The most common adverse events of any grade were peripheral sensory neuropathy, fatigue, nausea, neutropenia and diarrhoea. Treatment emergent peripheral neuropathy was experienced by 56 patients (55%). Eighty-eight percent of these patients experienced improvement of their peripheral neuropathy symptoms, including 73 percent with complete resolution. 

Brentuximab vedotin is being evaluated broadly in more than 70 ongoing clinical trials, including the Phase III ALCANZA trial and two additional Phase III studies, ECHELON-1 in frontline classical Hodgkin lymphoma and ECHELON-2 in frontline mature T-cell lymphomas, as well as trials in many additional types of CD30-expressing malignancies, including B-cell lymphomas. 

Article: Blood

Source: BusinessWire