By Connor Lynch

Pictured: Cancer patient in bed looking out window/iStock, Ridofranz
Biotech Seagen announced promising Phase III results Wednesday for its tyrosine kinase inhibitor Tukysa (tucatinib), in combination with Genentech’s antibody-drug conjugate Kadcyla (ado-trastuzumab emtansine), which met its primary endpoint of progression-free survival in HER-2 breast cancer patients.
The HER2CLIMB-02 trial was investigating the efficacy of Tukysa in combination with Genentech’s Kadcyla to treat locally advanced or metastatic HER-2 breast cancer that had received previous treatment with taxane and trastuzumab. While the trial met the primary endpoint of PFS, the study’s data on its secondary endpoint of overall survival “were not yet mature,” Seagen Chief Medical Officer Roger Dansey said in a statement. The combination arm of the trial also resulted in more discontinuation “due to adverse events,” but also noted that “no new safety signals emerged for the combination.”
Serious adverse reactions occurred in the study in 26% of patients, according to Seagen, with the most common being diarrhea, vomiting, nausea, abdominal pain, and seizure. Fatal adverse reactions occurred in 2% of patients receiving Tukysa, including sudden death, sepsis, dehydration, and cardiogenic shock.
The results overall were encouraging “including in patients with brain metastases,” Dansey said, adding that the company planned to present the full data “at an upcoming medical meeting and discuss the results with the FDA.”
Tukysa is a tyrosine kinase inhibitor which works by inhibiting phosphorylation of HER2 and HER3, a well-established biomarker of poor outcomes in gastric, breast, and colon cancers. This results in anti-tumor activity in HER-2 expressing tumor cells.
The drug already received FDA approval for treatment of HER-2-positive breast cancer in 2020 for patients who’ve already received an anti-HER-2-based treatment regimen. That was another strong year for Seagen, which cemented a deal with Merck for two of its cancer drugs. Merck paid $600 million up front, put in $1 billion in equity, and put up another $2.6 billion in milestone payments to develop ladiratuzumab vedotin, both as a monotherapy and in combination with Merck’s Keytruda to treat LIV-1-expressing tumors.
The pharma giant also paid $125 million up front and put up another $65 million in milestone payments to license Tukysa in Asia, the Middle East, Latin America, and other areas outside North America.
This latest news comes on the heels of more successes for Tukysa, which received accelerated approval from the FDA in January 2023 to treat RAS wild-type HER-2-positive metastatic colon cancer. That made the drug the first to be approved by the FDA for this particular cancer which, historically, has poor outcomes.
In March 2023, Pfizer acquired Seagen for $43 billion in a move aimed at merging Seagen’s antibody-drug conjugate technology with Pfizer’s strength and size “to advance the battle against cancer.”