- Seattle Genetics and Takeda Pharmaceutical's Adcetris added to chemo bested standard-of-care chemotherapy in a Phase 3 study of patients with previously CD30-expressing peripheral T-cell lymphoma, significantly extending progression-free survival.
- Patients in the Adcetris arm also showed markedly better outcomes on the study's secondary endpoints, including a 34% reduction in the risk of death compared to standard chemo. Seattle Genetics' stock price closed up more than 5% on Monday after the results were released.
- The ECHELON-2 trial data will be presented at the 2018 American Society of Hematology meeting in December. Both companies are planning on making regulatory submissions in the countries where they hold rights to the drug.
Adcetris (brentuximab vedotin) is an antibody-drug conjugate directed at the CD30 antigen, and is currently in dozens of clinical trials as either mono- or combination therapy.
The infusion is already FDA approved in five indications, including for previously untreated patients with classical Hodgkin lymphoma. In the later setting of relapsed/refractory Hodgkin lymphoma, Leerink estimates Adcetris has captured about 85% of the market.
Seattle Genetics and partner Takeda Pharmaceutical called the trial the first randomized Phase 3 study to show improvement in overall survival in frontline peripheral T-cell lymphoma, an aggressive type of non-Hodgkin lymphoma.
Around 4,000 patients with the CD30-expressing subtype are diagnosed each year in the U.S. Standard of care in PTCL has not changed in recent decades.
"These data showed a significant improvement in the primary endpoint of progression-free survival and all key secondary endpoints, including overall survival, along with a manageable safety profile," said Jesús Gomez-Navarro, head of oncology clinical research and development at Takeda said in a statement.
The overall survival benefit for the antibody-drug conjugate Adcetris was an unexpected bonus, according to Andrew Berens of Leerink, in a note to investors, and "should drive earlier and greater-than-anticipated penetration into PTCL."
"While we expected this trial to be successful based on strong data from the company's Phase 1 lead-in trial, we were not expecting a definitive overall survival benefit this early in the treatment," added Berens. "In our view, the 34% reduction in the risk of death obtained by using Adcetris instead of the standard of care chemotherapy regimen should drive robust penetration that could start with presentation of the detailed data at ASH."
Berens, however, pointed out that the data released so far does break out efficacy in anaplastic large cell lymphoma patients versus non-ALCL patients; the former make up around 25% of the PTCL population, and the trial was capped at 75% ALCL enrollment.
"Until the data are presented, the potential scope of the label may temper enthusiasm for these results," he wrote.
Adcetris includes a boxed warning for John Cunningham virus reactivation resulting in progressive multifocal leukoencephalopathy and death in rare cases.