Interim Results from Phase I Clinical Trial of ADCETRIS in Combination with Chemotherapy for Newly Diagnosed Advanced Stage Hodgkin Lymphoma Patients

Strategic Insights -

Seattle Genetics and Millennium: The Takeda Oncology Company announced interim results from a phase I clinical trial of ADCETRIS (brentuximab vedotin) in combination with chemotherapy for the treatment of newly diagnosed advanced stage Hodgkin lymphoma patients. The data were presented at the 53rd American Society of Hematology (ASH) Annual Meeting and Exposition in San Diego, CA. The trial was designed to establish the safety profile and maximum tolerated dose when adding ADCETRIS to ABVD or AVD chemotherapy regimens.

Key Takeaways:

  • No dose-limiting toxicity was observed at the maximum planned dose of ADCETRIS (1.2 milligrams per kilogram [mg/kg] every two weeks).
  • To date, no pulmonary toxicity events have been observed in the ADCETRIS plus AVD cohorts.
  • Ten out of 25 patients (40 percent) in the ADCETRIS plus ABVD cohorts had an event of pulmonary toxicity, including three Grade 3 and two Grade 4 events, which compares to an overall rate of pulmonary toxicity with bleomycin-based regimens reported in published literature of 10 to 25 percent.
  • Concomitant use of ADCETRIS with bleomycin is not recommended due to an increased incidence of pulmonary adverse events.
  • Among the 10 patients experiencing a pulmonary toxicity event in the ABVD combination cohorts, seven discontinued bleomycin and completed treatment with ADCETRIS plus AVD.
  • Across all treatment cohorts, the most common adverse events were neutropenia (77 percent), nausea (66 percent), peripheral sensory neuropathy (48 percent), fatigue (43 percent) and vomiting (43 percent).
  • Across all treatment cohorts, Grade 3 or higher adverse events were neutropenia (77 percent), anemia (14 percent), febrile neutropenia (11 percent) and pulmonary toxicity (11 percent, all in the ABVD cohorts).
  • All 15 patients who completed front-line therapy on study achieved a complete remission in the ADCETRIS plus ABVD cohorts.
  • Thirty-six of 37 evaluable patients in both study arms had negative interim PET scans after Cycle 2 as assessed by central review.

Statistics:

  • 25 patients were treated in the ADCETRIS plus ABVD cohorts.
  • 19 patients were treated in the ADCETRIS plus AVD cohorts.
  • The median age of patients across all cohorts of the trial was 32.5 years.
  • Enrollment of a total of 51 patients to the trial is complete.
  • Seattle Genetics and Millennium: The Takeda Oncology Company are planning a phase III clinical trial in advanced stage front-line Hodgkin lymphoma patients.

Sources:

  • Seattle Genetics and Millennium: The Takeda Oncology Company press release, December 13, 2011.
  • American Society of Hematology (ASH) Annual Meeting and Exposition, San Diego, CA, December 10-13, 2011.
  • Takeda Global Research & Development Centre (Europe) marketing authorization application for ADCETRIS, June 2011.
  • American Cancer Society, 2011 Cancer Facts & Figures.