Regulatory Decision Summary for Adcetris

In the Phase III Alcanza pivotal study, one hundred thirty-one patients with either primary cutaneous anaplastic large cell lymphoma (pcALCL) or CD30-expressing mycosis fungoides (MF) were randomized 1:1 to receive either Adcetris (N = 66) or physicians choice of either methotrexate or bexarotene (N =65). The primary efficacy outcome was the percentage of patients in each arm who achieved an objective response rate (ORR) lasting at least four months (ORR4). Progression-free survival (PFS) was a key secondary efficacy outcome.

An independent review facility (IRF) reported that 56% and 13% of patients randomized to the Adcetris and physicians choice arms, respectively, achieved an ORR4 on study. The ORR4 difference for Adcetris over physicians choice therapy was a statistically significant and clinically relevant benefit of 44%. A longer response time to Adcetris therapy in a larger proportion of the patient population including the reduction or disappearance of painful skin lesions was considered a clinically meaningful benefit. Decreases in lymph node and/or visceral site lesions as well as decreases in blood cancer cell counts were also reported in patients treated with Adcetris. The benefit in ORR4 was supported by an improvement in PFS for patients treated with Adcetris over physicians choice of therapy. The median PFS was 16.7 months for the Adcetris arm compared to 3.5 months for the physicians choice arm.

The safety of Adcetris in the Phase III Alcanza study was consistent with the known adverse reaction profile for this CD30-targeted anti-drug conjugated monoclonal antibody therapy. The majority of patients (61%) in the Adcetris arm had at least one dose delay and approximately one-quarter (26%) had at least one dose reduction. The most common adverse reactions leading to discontinuations and dose modifications were peripheral neuropathies - a well-recognized group of side effects of Adcetris therapy. One death on study was considered to be at least partly related to Adcetris (pancreatitis and gastrointestinal perforation). No major safety updates to the Product Monograph were implemented based on the results of this study.

Overall, the efficacy and safety of Adcetris was positive for the treatment of adult patients with pcALCL or CD30-expressing MF who have had prior systemic therapy. A Notice of Compliance (NOC) was recommended.