No published evidence of safety

Serious adverse effects reported in adults

Low levels anticipated in milk due to the drug’s properties and likely to be degraded in infant’s GI tract. However, the effects on the infant of even small amounts in breast milk are unknown

May 20 · Approved in EU [14].

Mar 20 · Recommended for EU approval by CHMP - the additional indication is "in combination with cyclophosphamide, doxorubicin and prednisone (CHP) ... for adult patients with previously untreated systemic anaplastic large cell lymphoma (sALCL) [13].

Jul 19 · Has been filed in EU [12].

Nov 18 · In the US, the FDA used a new review program (The Real-Time Oncology Review (RTOR) program) to quickly approve use of brentuximab vedotin (Adcetris) in combination with chemotherapy for adults with certain types of peripheral T-cell lymphoma (PTCL) [10].

Nov 18 · FDA grants Breakthrough Therapy Designation to brentuximab vedotin for previously untreated systemic anaplastic large cell lymphoma or other CD30-expressing peripheral T-cell lymphomas (PTCL), including angioimmunoblastic T-cell lymphoma and PTCL not otherwise specified, in combination with CHP (cyclophosphamide, doxorubicin, and prednisone) [9].

Nov 18 · Application for supplemental Biologics License Application (BLA) made to the U.S. Food and Drug Administration (FDA) based on data from the phase 3 ECHELON-2 trial [8].

Oct 18 · The companies announced plans to submit a NDA to the US FDA for PTCL before end of year [7].

Oct 15 · PIII development continues [4].

Peripheral T-cell lymphoma affects < 1 in 10,000 people in the EU; equivalent to a total of fewer than 51,000 people [EMA]

Dec 18 · PIII ECHELON-2 published. Median progression-free survival was 48.2 months in the Brentuximab+CHP group and 20.8 months in the CHOP group (p=0.011) [11].

Oct 18 · Positive results from PIII ECHELON-2 trial announced. The randomized, double-blind, placebo-controlled multiccentre trial enrolled ~450 pts. Brentuximab Vedotin + CHP (cyclophosphamide, doxorubicin, prednisone) vs. CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone), achieved the primary endpoint, demonstrating improvement in Progression-Free Survival (hazard ratio=0.71; p=0.0110). Improvements were achieved in all Key secondary endpoints, including overall survival.[7]

Feb 18 · NCT01777152 due to complete Dec 18 [6].

Dec 16 · NCT01777152 ECHELON-2 Data are expected in 2017 to 2018 timeframe. [5]

Mar 15 · PIII ECHELON-2 study still rectruiting - no results have been reported [3].

Mar 13 · The PIII study (NCT01777152) is enrolling 300 patients. The estimated completion date is Dec 19 with primary outcome data available Dec 17 [2].

Jan 13 · The PIII global ECHELON-2 study evaluating brentuximab vedotin in combination with chemotherapy in patients with newly diagnosed CD30-positive mature T-cell lymphoma (MTCL), including patients with systemic anaplastic large cell lymphoma (sALCL) and other types of peripheral T-cell lymphomas has started. The trial has a Special Protocol Assessment (SPA) agreement from FDA and has received scientific advice from the EMA. In the randomized, double-blind, study, brentuximab in combination with cyclophosphamide, doxorubicin and prednisone (A+CHP) will be compared to cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) as 1st-line therapy in 300 patients with CD30-expressing MTCL. The primary endpoint is progression-free survival per independent review facility assessment. Secondary endpoints include overall survival (OS), complete remission (CR) rate and safety. A molecular companion diagnostic test will be used to identify eligible patients based on CD30 expression; this is being developed in collaboration with Ventana Medical Systems [1].

NICE draft scope

NICE scope

NICE technology appraisal

NIHR

SMC