Updated ALCANZA trial results presented at American Society of Hematology (ASH)

Seattle Genetics, Inc. highlighted updated results from the phase III ALCANZA clinical trial evaluating Adcetris (brentuximab vedotin) in CD30-expressing cutaneous T-cell lymphoma (CTCL) at the 59th American Society of Hematology (ASH) Annual Meeting and Exposition taking place in Atlanta, Georgia, December 9-12, 2017. The presentation highlighted longer-term durability data from the phase III ALCANZA clinical trial of single-agent Adcetris for the treatment of patients with primary cutaneous anaplastic large cell lymphoma (pcALCL) or CD30-expressing mycosis fungoides (MF). Together, these comprise approximately 70 percent of CTCL diagnoses and the majority of patients who require systemic therapy.

“The updated analyses from the phase III ALCANZA clinical trial presented at this year’s ASH annual meeting are based on longer-term follow-up by investigators. Since the initial presentation at the ASH Annual Meeting in 2016, the ALCANZA results continue to show superior clinical efficacy of Adcetris over standard-of-care therapies in patients with CD30-expressing CTCL,” said Jonathan Drachman, M.D., Chief Medical Officer and Executive Vice President, Research and Development at Seattle Genetics.

Updated Analyses of the International, Open-Label, Randomized, Phase III ALCANZA Study: Longer-term Evidence for Superiority of Brentuximab Vedotin Versus Methotrexate or Bexarotene for CD30-Positive Cutaneous T-Cell Lymphoma (Abstract #1509, poster presentation on Saturday, December 9, 2017), ALCANZA was a randomized, open-label phase III study designed to evaluate single-agent Adcetris versus a control arm of investigator’s choice of standard of care therapies, methotrexate or bexarotene, in patients with CD30-expressing pcALCL or MF. Patients with pcALCL must have received at least one prior systemic or radiation therapy and patients with MF must have received at least one prior systemic therapy.

A total of 131 patients were randomized with 128 patients in the intent-to-treat population. Sixty-four patients were assigned to the Adcetris arm and 64 patients were assigned to the control arm. Patients received Adcetris or investigator’s choice of methotrexate or bexarotene for up to approximately one year. Data from longer-term patient follow-up per investigator assessment in the phase III ALCANZA trial after a median observation time of 33.9 months from the first dose of Adcetris versus physician’s choice include:

1.The trial achieved its primary endpoint of demonstrating a highly statistically significant improvement in the rate of objective response lasting at least four months (ORR4) in the Adcetris arm versus the control arm. The ORR4 per investigator assessment was 60.9 percent in the Adcetris arm compared to 7.8 percent in the control arm (p-value <0.001).

2.The key secondary endpoints per investigator, including complete response (CR) rate, progression-free survival (PFS) and reduction in the burden of symptoms during treatment (per Skindex-29 questionnaire), continued to be all highly statistically significant in favor of the Adcetris arm.

3.The median PFS per investigator in the Adcetris arm was 15.8 months compared to 3.6 months in the control arm (HR 0.373; 95% CI, 0.245-0.569; p-value <0.001).

4. The CR rate in the Adcetris arm was 18.8 percent compared to zero percent in the control arm (p-value <0.001). 5. Patient-reported quality of life assessed by the Skindex-29 questionnaire showed significantly greater symptom reduction for patients in the Adcetris arm versus the control arm (mean maximum change of -28.08 vs -8.62; p-value <0.001).

At time of the analyses, 47 patients (73 percent) in the Adcetris arm and 48 patients (75 percent) in the physician’s choice arm had received one or more subsequent skin-directed or systemic therapy. The median time to next treatment in the Adcetris arm was significantly longer at 14.2 months compared with the physician’s choice arm at 6.1 months (p-value <0.001). In the Adcetris versus physician’s choice arms, the probability of patients not requiring subsequent skin-directed or systemic therapy was greater at one year (65.5 percent vs. 15.3 percent) and two years (24.6 percent vs. 4.4 percent).

Peripheral neuropathy events were observed in 44 of 66 patients (67 percent) in the Adcetris arm and four of 62 patients (six percent) in the physician’s choice arm. In the Adcetris arm, 86 percent of patients reported resolution or improvement in peripheral neuropathy events, with 59 percent reporting resolution of all events after a median of 30 weeks and 27 percent reporting some improvement after a median of 13 weeks. Eighteen patients had ongoing peripheral neuropathy events, including 15 patients with Grade 1 and three patients with Grade 2. In November 2017, the FDA approved Adcetris for the treatment of adult patients with pcALCL or CD30-expressing MF who have received prior systemic therapy based on the results of the phase III ALCANZA clinical trial.