With trial win, Seagen's breast cancer drug Tukysa boosts Roche's Kadcyla—and Pfizer's $43B buyout

Pfizer is shelling out $43 billion to acquire Seagen primarily for the Seattle biotech’s antibody-drug conjugate (ADC) capabilities. But a trial win for a small-molecule cancer drug makes the deal more attractive.

Seagen on Wednesday said a phase 3 trial testing a combination of its Tukysa and Roche’s Kadcyla has hit its main goal in patients with previously treated HER2-positive breast cancer.

Compared with Kadcyla and placebo, the combo significantly reduced the risk of tumor progression or death, Seagen said. Data on patient survival remain immature.

Seagen plans to share the detailed results from the HER2CLIMB-02 trial at a medical meeting and will discuss them with the FDA, the company’s R&D chief, Roger Dansey, said in a statement.

The positive results further de-risk the Seagen acquisition by Pfizer, Leerink Partners analysts said in a Wednesday note.

Since securing FDA approval in 2020, Tukysa has been used alongside trastuzumab (Herceptin) and chemo to treat HER2-positive breast cancer after at least one prior treatment in the metastatic setting. Kadcyla, as an ADC, essentially uses Herceptin as a guiding agent to bring a chemo drug specifically to HER2-expressing cancer cells.

While ADCs are typically more powerful than their corresponding antibody drugs, they also come with additional toxicitiy. Regarding safety in HER2CLIMB-02, patients discontinued treatment with the combo because of side effects more often than they did in the control group. But Seagen said investigators detected no new safety signals.

The HER2CLIMB-02 trial shows Tukysa can add benefit to an antibody-drug conjugate, an important showing as the breast cancer area becomes increasingly competitive, the Leerink team said.

Both Tukysa and Kadcyla are HER2-targeted agents, and both are under pressure from AstraZeneca and Daiichi Sankyo’s ADC Enhertu, which has handily beaten Kadcyla in a head-to-head trial. After that resounding defeat in previously treated disease, Kadcyla has been clinching onto its postsurgical use in early-stage breast cancer and geographic expansion.

As for Tukysa, Seagen has been touting the small-molecule drug’s ability to control brain metastases as a differentiator from competitors. In his Wednesday statement, Dansey said he’s encouraged by the combo results, including in patients with brain metastases.

Now that Tukysa can boost Kadcyla on progression-free survival (PFS), a key question is the combo’s magnitude of improvement compared with Enhertu’s showing on this metric. In the Desinty-Breast03 trial between Enhertu and Kadcyla, Enhertu reduced the risk of progression or death by a whopping 67% after a long-term follow-up. Median PFS for Enhertu was 28.8 months, versus 6.8 months for Kadcyla.

As the Leerink analysts noted, the Tukysa-Kadcyla pairing showed a median PFS of 8.2 months in a phase 1b trial. Cross-trial comparisons should be considered with a grain of salt because of different patient populations. In both Destiny-Breast03 and the Seagen phase 1b trial, patients had tried a median two prior lines of therapy. But their brain metastases exclusion criteria were different.

The current HER2CLIMB-02 readout also invites the question of whether Tukysa’s benefit on top of an ADC applies to Enhertu as well—or Seagen’s own HER2 ADC, the RemeGen-partnered disitamab vedotin.

Seagen has a broad development plan for Tukysa. Its program includes a phase 2 trial coded HER2CLIMB-04 that pairs Tukysa with Enhertu in second-line HER2-positive breast cancer. The phase 3 HER2CLIMB-05 trial is testing Tukysa in addition to Herceptin and Roche’s Perjeta as a first-line maintenance regimen.