Clinical Trials

Date: 2016-07-18

Type of information: Publication of results in a medical journal

phase: 2

Announcement: publication of results in Blood

Company: Seattle Genetics (USA - WA) Takeda Pharmaceutical (Japan)

Product: Adcetris® (brentuximab vedotin)

Action mechanism:

• monoclonal antibody/antibody drug conjugate (ADC). Adcetris® (brentuximab vedotin) is an antibody-drug conjugate (ADC) comprising an anti-CD30 monoclonal antibody attached by a protease-cleavable linker to a microtubule disrupting agent, monomethyl auristatin E (MMAE). The ADC employs a linker system that is designed to be stable in the bloodstream but to release MMAE upon internalisation into CD30-expressing tumor cells. The CD30 antibody part of the product acts as a carrier for the cytotoxic substance. When the antibody attached by the linker to the cytotoxin attaches to the CTCL cells, it is taken up by the cells. Once inside the cancer cells, the linker is cut and the cytotoxic molecule, monomethyl auristatin E, gets released and stops cell division. The cancer cells are then expected to undergo programmed cell death.
• In 2012, the FDA granted Adcetris® orphan drug designation for the treatment of mycosis fungoides (MF), which is the most common type of CTCL.
• Adcetris® is being evaluated globally as the foundation of therapy for Hodgkin lymphoma in more than 45 ongoing corporate- and investigator-sponsored clinical trials.

Disease: relapsed or refractory systemic anaplastic large cell lymphoma (ALCL)

Therapeutic area: Cancer - Oncology

Country:

Trial details:

Latest news:

• • On July 18, 2016, Seattle Genetics and Takeda Pharmaceutical announced the final data of the Adcetris® (brentuximab vedotin) monotherapy pivotal Phase 2 clinical trial in relapsed or refractory classical Hodgkin lymphoma were published in the journal Blood. The manuscript, which summarizes the five-year, end-of-study results, highlights that patients who attained a complete response achieved long-term disease control. The manuscript is available online today and will be included in a future print edition of Blood.  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 diarrhea. 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. • On December 7, 2014, Seattle Genetics and Takeda Pharmaceutical announced four-year overall survival (OS) data from the Adcetris® (brentuximab vedotin) pivotal Phase 2 clinical trial in relapsed or refractory systemic anaplastic large cell lymphoma (ALCL). Adcetris® is an antibody-drug conjugate (ADC) directed to CD30, which is expressed in classical Hodgkin lymphoma (HL) and systemic ALCL, a type of T-cell lymphoma. At a median follow up of 46.3 months, the estimated four-year survival rate was 64 percent. The data were presented at the 56th American Society of Hematology (ASH) Annual Meeting and Exposition taking place in San Francisco, CA, December 6-9, 2014.
• Four-Year Survival Data from an Ongoing Pivotal Phase 2 Study of Brentuximab Vedotin in Patients with Relapsed or Refractory Systemic Anaplastic Large Cell Lymphoma (Abstract #3095): A pivotal, single-arm clinical trial was conducted in 58 relapsed or refractory systemic ALCL patients to assess the efficacy and safety of single-agent ADCETRIS. In addition, the trial was designed to determine duration of response, progression-free survival (PFS) and overall survival (OS). Patients received 1.8 milligrams per kilogram (mg/kg) of ADCETRIS administered through a 30-minute intravenous infusion every three weeks for up to 16 cycles. As previously reported, 86 percent of patients on the trial achieved an objective response, including 59 percent with a complete response (CR) and 28 percent with a partial response (PR).
• Data from long-term patient follow up in this pivotal trial will be highlighted by Barbara Pro, M.D., Thomas Jefferson University, and include:
• After a median observation time of 46.3 months from the first dose of ADCETRIS, the median OS was 55.1 months and the estimated four-year OS was 64 percent. The median PFS per investigator was 20.0 months. Nineteen of 38 patients (50 percent) who achieved a CR on study per investigator assessment remained in remission at the time of last follow-up; for all patients who achieved a CR, median OS and PFS had not yet been reached. For the 16 CR patients who received a consolidative transplant (either allogeneic or autologous stem cell transplant), neither median PFS nor OS had been reached.

Is general: Yes