Successful Phase III ALCANZA clinical trial evaluating Adcetris (brentuximab vedotin) in patients with cutaneous T-cell lymphoma (CTCL). - Takeda and Seattle Genetics.

Takeda Pharmaceutical Company Limited and Seattle Genetics, Inc. announced that data from the Phase III ALCANZA clinical trial evaluating Adcetris (brentuximab vedotin) in patients with cutaneous T-cell lymphoma (CTCL) was presented in an oral session at the 58th American Society of Hematology (ASH) annual meeting on Saturday, December 3 at 2:15 p.m. PT. Topline data were reported in August 2016 demonstrating the ALCANZA trial met its primary endpoint of achieving a highly statistically significant improvement in the rate of objective response lasting at least four months (ORR4). Based on the study results, the FDA granted Breakthrough Therapy Designation to Adcetris for the treatment of the most common subtypes of CTCL, mycosis fungoides (MF) and primary cutaneous anaplastic large cell lymphoma (pcALCL). Adcetris is an antibody-drug conjugate (ADC) directed to CD30 which is expressed on skin lesions in approximately 50 percent of patients with CTCL. Adcetris is currently not approved for the treatment of CTCL.

"Brentuximab Vedotin Demonstrates Significantly Superior Clinical Outcomes in Patients with CD30-Expressing Cutaneous T Cell Lymphoma Versus Physician's Choice (Methotrexate or Bexarotene): The Phase III ALCANZA Study "-(Abstract #182, oral presentation December 3, 2016 at the San Diego Convention Center, Room 6AB)Key findings, were presented by Dr. Youn Kim, Stanford University, include: 1.The trial achieved its primary endpoint and the Adcetris treatment arm demonstrated a highly statistically significant improvement in the ORR4 versus the control arm as assessed by an independent review facility. The ORR4 was 56.3 percent in the Adcetris arm compared to 12.5 percent in the control arm (p-value <0.0001).2. The key secondary endpoints specified in the protocol, including complete response (CR) rate, progression-free survival (PFS) and reduction in the burden of symptoms during treatment (per Skindex-29), were all highly statistically significant in favor of the Adcetris arm. 3. The median PFS in the Adcetris arm was 16.7 months compared to 3.5 months in the control arm (HR 0.270; 95% CI, 0.169, 0.430; p-value <0.0001). 4. The CR rate in the Adcetris arm was 15.6 percent compared to 1.6 percent in the control arm (p-value = 0.0046). 5. The Skindex-29 symptom domain showed a mean max reduction of -27.96 in the Adcetris arm compared to -8.62 in the control arm (p-value <0.0001). There was a difference in mean maximum reduction of -18.9 (95% CI, -26.6, -11.2). 6. Patients received a median of 12 cycles (36 weeks) of Adcetris versus 17 weeks of bexarotene or nine weeks of methotrexate.7. The safety profile associated with Adcetris from the ALCANZA trial was generally consistent with the existing prescribing information. 9.The majority of the peripheral neuropathy events were grade 1 or 2 (26 percent and 32 percent, respectively). Peripheral neuropathy events were observed in nine percent at grade 3 and no grade 4 events were reported. Eighty-two percent of patients reported resolution or improvement in peripheral neuropathy events in the in the Adcetris arm at a median of 22.9 months of follow-up. 10.Discontinuation due to adverse events occurred in 24 percent of patients in the Adcetris arm compared to eight percent in the control arm. Serious adverse events were comparable between the Adcetris arm and the control arm (29 percent in each). Four deaths in the Adcetris arm (three unrelated to study drug) occurred within 30 days of the last dose.