Seattle Genetics has shared more of the tucatinib data it hopes will win it approval in HER2-positive breast cancer. The pivotal trial linked the tyrosine kinase inhibitor to reduced risk of progression and death in patients with and without brain metastases, leading Seattle Genetics CEO Clay Siegall to hail the data as “stunning.”
Investigators enrolled 612 women with locally advanced or metastatic HER2-positive breast cancer who had on average received four lines of prior therapy. The patients, close to half of whom had brain metastases, were no longer responding to Roche’s HER2 drugs Herceptin, Perjeta or Kadcyla.
In that hard-to-treat population, adding tucatinib to Herceptin and capecitabine was associated with a 46% reduction in the risk of disease progression or death over the backbone regimen alone. In the subgroup of patients with brain metastases, the reduction in risk of disease progression or death was bigger still at 52%. Seattle Genetics is happy with the results.
“Take those groups and you’ve about prevented about half of the progression and deaths and so it’s pretty stunning,” Siegall said at the American Society of Hematology (ASH) 2019 annual meeting.
Seattle Genetics went from ASH to the 2019 San Antonio Breast Cancer Symposium, where it shared detailed data from its pivotal tucatinib trial. The data add nuance to the headline results shared in October, revealing, for example, that the estimated progression-free survival for patients with brain metastases at one year was 25% in the tucatinib group and 0% in the control arm.
Despite the proliferation of drugs approved in HER2-positive breast cancer, the sizable subpopulation of patients with brain metastases remains underserved.
“The impact on the brain metastases associated with breast cancer was especially great to see because there’s not been any drugs that have shown efficacy in pre-existing brain metastases and that’s what’s unique about this,” Siegall said.
Puma Biotechnology is working to show Nerlynx, which is already approved, works in patients with brain metastases, picking up orphan drug status in the indication earlier this year. However, Nerlynx suffers from tolerability problems that may make it less appealing than tucatinib.
The FDA label for Nerlynx states 40% of people who received the drug in a pivotal trial suffered grade 3 diarrhea. In Seattle Genetics’ trial, 13% of patients on tucatinib had grade 3 diarrhea. At around 5%, the proportion of people on tucatinib with elevated liver enzymes was higher than in the Nerlynx trial. However, discontinuations due to elevated liver enzymes were rarer in the tucatinib trial.
Seattle Genetics plans to file for approval in the U.S. and Europe in the first quarter of 2020, although it is trying to pull that date forward and ensure patients can access the drug while it it is awaiting a regulatory decision.
“We’re working extremely hard and close with FDA to submit and we said we would submit as fast as we can, certainly by early next year at the latest. It’s just too important to get this done and out on the market. We are going to set up an expanded access plan until approval for patients in the U.S. because it’s a meaningful drug,” Siegall said.
Approval would further validate Seattle Genetics' decision to buy Cascadian Therapeutics. Seattle Genetics paid more than $600 million to acquire Cascadian last year, in large part to get its hands on tucatinib. The deal moved Seattle Genetics beyond its focus on antibody-drug conjugates and gave it another late-phase solid tumor prospect.