Are Zedoresertib and Lunresertib an Efficacious Combo Across Solid Tumors?

Results from the first-in-human phase 1 MYTHIC trial (NCT04855656) demonstrated that combining the WEE1 inhibitor zedoresertib with the PKMYT1 inhibitor lunresertib achieved an overall response rate (ORR) of 18.5% via RECIST criteria in patients with CCNE1, FBXW7, and PPP2R1A-altered cancers.¹ In patients with resistant/refractory ovarian cancer, the ORR was 33.3% across all dose levels and 50% at the potential recommended phase 2 dose.

These data were presented by Timothy A. Yap, MBBS, PhD, FRCP, at the 2026 American Association for Cancer Research Annual Meeting. Following his presentation, Yap joined CancerNetwork^® for a discussion where he highlighted some of the most interesting takeaways from the trial. According to Yap, the disease states evaluated in this trial represent areas of unmet need, where no specific standard-of-care options can target these alterations.

Notably, based on results from this trial, the FDA granted fast track designation to lunresertib in combination with zedoresertib in patients with genomic-defined platinum-resistant ovarian cancer.²

Yap is a medical oncologist and physician-scientist; the Random Horne, Jr. Endowed Professor for Cancer Research; and vice president and head of clinical development in the Therapeutics Discovery Division, all at The University of Texas MD Anderson Cancer Center.

References

1. Yap TA, Aggarwal R, Fontana E, et al. First data disclosure of the phase I trial of the first in class combination of WEE1 inhibitor zedoresertib with PKMYT1 inhibitor lunresertib in patients with advanced solid tumors harboring CCNE1, FBXW7, or PPP2R1A genomic alterations. Abstract presented at: American Association for Cancer Research Annual Meeting 2026; April 17-22, 2026; San Diego, CA. Abstract CT022.
2. Following oral presentation of phase I data at AACR 2026, Debiopharm announces FDA fast track designation for lunresertib in combination with zedoresertib for genomic-defined platinum-resistant ovarian cancer. News release. Debiopharm. April 20, 2026. Accessed May 4, 2026. https://shorturl.at/n1bWn