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Brentuximab vedotin
The US Food and Drug Administration (FDA) has granted breakthrough therapy designation to brentuximab vedotin (BV, Adcetris) for use in combination with chemotherapy as frontline treatment of advanced classical Hodgkin lymphoma (HL).
Seattle Genetics and Takeda plan to submit a supplemental biologics license application seeking approval for BV in this indication before the end of this year.
The breakthrough designation is based on positive topline results from the phase 3 ECHELON-1 trial.
Full results from this trial are expected to be presented at the 2017 ASH Annual Meeting in December.
BV is an antibody-drug conjugate consisting of an anti-CD30 monoclonal antibody attached by a protease-cleavable linker to a microtubule disrupting agent, monomethyl auristatin E.
BV is currently FDA-approved to treat:
- Classical HL after failure of autologous hematopoietic stem cell transplant (auto-HSCT) or after failure of at least 2 prior multi-agent chemotherapy regimens in patients who are not auto-HSCT candidates
- Classical HL patients at high risk of relapse or progression as post-auto-HSCT consolidation.
BV also has accelerated approval from the FDA for the treatment of systemic anaplastic large-cell lymphoma after failure of at least 1 prior multi-agent chemotherapy regimen. This approval is based on overall response rate. Continued approval of BV for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
ECHELON-1 trial
In this phase 3 trial, researchers compared BV in combination with doxorubicin, vinblastine, and dacarbazine to a recognized standard of care chemotherapy regimen in patients with previously untreated, advanced classical HL.
The study enrolled 1334 patients who had a histologically confirmed diagnosis of stage III or IV classical HL and had not been previously treated with systemic chemotherapy or radiotherapy.
The study’s primary endpoint is modified progression-free survival (PFS) per an independent review facility. Modified PFS is defined as the time to progression, death, or receipt of additional anticancer therapy for patients who are not in complete response after completion of frontline therapy.
There was a significant improvement in modified PFS in the BV arm compared to the control arm (hazard ratio=0.770; P=0.035). The 2-year modified PFS rate was 82.1% in the BV arm and 77.2% in the control arm.
An interim analysis of overall survival revealed a trend in favor of the BV arm.
The safety profile of BV plus chemotherapy was consistent with the profile known for the single-agent components of the regimen.
About breakthrough designation
The FDA’s breakthrough designation is intended to expedite the development and review of new treatments for serious or life-threatening conditions.
The designation entitles the company developing a therapy to more intensive FDA guidance on an efficient and accelerated development program, as well as eligibility for other actions to expedite FDA review, such as rolling submission and priority review.
To earn breakthrough designation, a treatment must show encouraging early clinical results demonstrating substantial improvement over available therapies with regard to a clinically significant endpoint, or it must fulfill an unmet need.
