RE:RE:RE:AstraZeneca's ADC disappoints - on severe adverse eventsDecember 06, 2023 - As antibody-drug conjugates (ADCs) grow their importance in the oncology treatment space, efforts are underway to combine them with other agents.
A negative overall survival trend has become a big no-no at the FDA lately. The agency has required long-term data, limited the scope of an approval, or forced market withdrawals based on any hint of data suggesting a potential harm to survival.
Unlike the positive tumor progression signal, the Seagen Tukysa- Roche Kadcyla regimen preliminarily showed a 23% increased risk of death after a median follow-up of 24.4 months. In HER2CLIMB-02, grade 3 or above treatment-emergent adverse events were higher at 69% in the combo arm, versus 41% in control.
There’s another weakness in the HER2CLIMB-02 trial, the American Association for Cancer Research, the organizer of SABCS, noted in its own release. The Tukysa combo was not pitted against AstraZeneca and Daiichi Sankyo’s Enhertu, which has recently become the preferred agent over Kadcyla in the second-line HER2-positive setting.
As for the proper ADC partner with Tukysa, Seagen is running a small phase 2 trial coded HER2CLIMB-04 that combines Tukysa with Enhertu in the second-line setting. The trial has a primary completion date in January 2024, according to ClinicalTrials.gov. Seagen also has its own HER2 ADC, disitamab vedotin, in-licensed from RemeGen.
Seagen is currently being acquired by Pfizer in a $43 billion deal.
https://www.fiercepharma.com/pharma/seagen-depicts-tukysa-value-roche-adc-breast-cancer-fda-path-remains-unclear