Clinical Trials

Date: 2014-12-08

Type of information: Presentation of results at a congress

phase:

Announcement: presentation of results at the 56th American Society of Hematology (ASH) Annual Meeting and Exposition, being held December 6-9 in San Francisco, CA

Company: Seattle Genetics (USA - WA)

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. The anti-tumour activity of brentuximab-vedotin has been established in the HL and sALCL study populations as well as in the relapsed or refractory HL patients ineligible for ASCT/multidrug chemotherapy. The different clinical endpoints demonstrated clinical benefit in terms of disease control, resolution of B-symptoms and in terms of enabling further potentially curative treatment options.

Disease: diffuse large B-cell lymphoma

Therapeutic area: Cancer - Oncology

Country:

Trial details:

Latest news:

• • On December 8, 2014, Seattle Genetics highlighted two separate Adcetris® (brentuximab vedotin) data presentations in relapsed/refractory and frontline diffuse large B-cell lymphoma (DLBCL) at the 56th American Society of Hematology (ASH) Annual Meeting and Exposition taking place in San Francisco, CA, December 6-9, 2014.  Brentuximab Vedotin Monotherapy in DLBCL Patients with Undetectable CD30: Preliminary Results from a Phase 2 Study (Abstract #629): An ongoing phase 2 clinical trial in relapsed or refractory DLBCL includes three treatment arms to evaluate ADCETRIS in CD30-positive disease, CD30-undetectable disease and in combination with Rituxan (rituximab). Data were reported from 51 patients with CD30-undetectable DLBCL using standard immunohistochemistry (IHC) testing. The median age of patients was 65 years, 71 percent were refractory to frontline therapy and 61 percent were refractory to their most recent prior therapy. Patients were treated with single-agent ADCETRIS every three weeks. The trial was designed to assess the antitumor activity and safety profile and evaluate CD30 expression.
• Key findings presented by Tanya Siddiqi, M.D., City of Hope National Medical Center, include: Of 42 evaluable patients in the CD30-undetectable DLBCL arm treated with single-agent Adcetris®, 13 patients (31 percent) had an objective response, including four patients (10 percent) with a complete remission and nine patients (21 percent) with a partial remission.Median progression-free survival was 1.4 months (range, 0.4 to 9+). Median duration of response had not yet been reached for patients with a complete remission and was 1.6 months for patients with a partial remission. Among 35 patients with baseline and post-baseline assessments, 63 percent achieved tumor reduction.
• The most common adverse events of any grade occurring in greater than 15 percent of patients were nausea (29 percent); fatigue and peripheral sensory neuropathy (22 percent each); anemia and constipation (20 percent each); diarrhea and neutropenia (18 percent each); and abdominal pain and pyrexia (16 percent each). The most common Grade 3 or 4 adverse events occurring in more than one patient were neutropenia (seven patients), anemia (three patients) and diarrhea and febrile neutropenia (two patients each). Updated efficacy data were also reported from 48 DLBCL patients in the CD30-positive arm treated with single-agent Adcetris® demonstrating a 44 percent objective response rate, including 17 percent complete remissions, and a median progression-free survival of 4.0 months (range, 0.6+ to 24+). Based on the activity demonstrated by Adcetris® in relapsed/refractory DLBCL, the company plans to initiate a randomized phase 2 trial during 2015 for patients with CD30-positive DLBCL who have relapsed following autologous stem cell transplant or who are ineligible for transplant. This trial will randomize patients to receive Rituxan and bendamustine with or without Adcetris®.
• Brentuximab Vedotin in Combination with RCHOP as Front-line Therapy in Patients with DLBCL: Interim Results from a Phase 2 Study (Abstract #1745): Data were reported from an ongoing phase 2 clinical trial evaluating Adcetris® in combination with the standard of care regimen consisting of rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (A+RCHOP) in frontline high-intermediate and high-risk DLBCL patients. Patients were randomized to receive standard dose RCHOP with either 1.2 milligrams per kilogram (mg/kg) or 1.8 mg/kg of Adcetris® every three weeks.
• Data were reported from 47 patients with a median age of 67 years. Nearly all patients (95 percent) had stage III/IV disease at the time of diagnosis and were considered either high-risk (38 percent) or high-intermediate risk (62 percent). As a part of the trial design, a Safety Monitoring Committee reviewed safety data after ten patients in each arm had completed treatment, and recommended continuing with a dose of 1.2 mg/kg of Adcetris®. Interim data from this phase 2 trial were highlighted in a poster presentation by Christopher Yasenchak, M.D., Willamette Valley Cancer Institute and Research Center/US Oncology Research, include: Of 22 patients in both arms evaluable for response, 21 patients (95 percent) had an objective response, including 17 patients (77 percent) with a complete remission and four patients (18 percent) with a partial remission. One patient had progressive disease. Antitumor activity was not significantly different between the two dosage arms. In the arm with the recommended dose of 1.2 mg/kg of Adcetris® plus RCHOP, all 13 evaluable patients had an objective response, including eight patients (80 percent) with a complete remission and two patients (20 percent) with a partial remission.
• Preliminary data suggest a higher complete remission rate in CD30-positive patients (greater than 90 percent) versus CD30-undetectable DLBCL patients. Across both treatment arms, 100 percent of patients achieved tumor reduction. Adcetris®administered at 1.2 mg/kg in combination with RCHOP had a similar safety profile to that expected from RCHOP alone in this patient population. The most common adverse events occurring in more than 25 percent of patients of any grade in the RCHOP plus 1.2 mg/kg of Adcetris® arm were nausea (38 percent), fatigue and diarrhea (33 percent each), anemia (30 percent), peripheral sensory neuropathy and febrile neutropenia (29 percent each). The most common Grade 3 or 4 adverse events in the RCHOP plus 1.2 mg/kg of Adcetris® arm were neutropenia, febrile neutropenia, anemia, weight loss and insomnia. The company plans to add a cohort of CD30-positive DLBCL patients to this trial evaluating Adcetris® plus RCHP (removing vincristine from the regimen) to support future development of Adcetris® in frontline DLBCL.

Is general: Yes