Seagen's Tukysa showed it can add benefit to an antibody-drug conjugate, an important showing as the breast cancer area becomes increasingly competitive, Leerink Partners analysts said.
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.
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.
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.
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 HER2ADC, the RemeGen-partnered disitamab vedotin.