Dr Timothy Yap speaks to ecancer about a first-in-human data on the combination of zedoresertib, a WEE1 inhibitor, and lunresertib, a PKMYT1 inhibitor, in patients with molecularly defined advanced solid tumours.

This novel synthetic lethal approach demonstrated encouraging antitumor activity, with over half of evaluable patients experiencing tumor shrinkage.

Particularly strong responses were seen in ovarian cancer, where the majority of patients achieved meaningful clinical benefit, including complete and partial responses.

The safety profile was manageable, with expected haematologic and skin-related toxicities and no treatment-related deaths. Pharmacodynamic analyses confirmed target engagement and biological activity consistent with the proposed mechanism.

These findings support further development of this first-in-class combination, especially in patients with CCNE1 amplification or FBXW7 mutations, where therapeutic options remain limited.