MYTHIC Trial Demonstrates Efficacy in Platinum-Resistant Ovarian Cancer

At the 2026 American Association for Cancer Research (AACR) Annual Meeting, Timothy A. Yap, MBBS, PhD, FRCP, shared results from the first-in-human phase 1 MYTHIC trial (NCT04855656) evaluating zedoresertib, a WEE1 inhibitor, in combination with lunresertib, a PKMYT1 inhibitor, as a treatment for patients with solid tumors harboring CCNE1, FBXW7, and PPP2R1A genomic alterations.¹

Yap, a medical oncologist and physician-scientist, as well as the Random Horne, Jr. Endowed Professor for Cancer Research and vice president and head of Clinical Development in the Therapeutics Discovery Division at UT MD Anderson Cancer Center, spoke with CancerNetwork® about these findings after the meeting.

In the overall population of patients with platinum-resistant/refractory ovarian cancer, the investigational agent achieved an overall response rate (ORR) of 37.5% across all dose levels. Efficacy improved for those treated at the potential recommended phase 2 dose (RP2D), where the ORR reached 50%. Clinical benefit extended beyond objective responses, as 80% of patients experienced tumor shrinkage. Furthermore, the responses appeared durable; 37% of patients remained on treatment for longer than 16 weeks. Yap also noted that 3 additional partial responses have been observed since the data cutoff of March 25, 2026.

The MYTHIC trial demonstrated even higher activity in the subgroup of patients with CCNE1-amplified ovarian cancer. Among 19 patients in this subset, the ORR across all dose levels was 42.1%. Most notably, the ORR at the potential RP2D increased to 60% for these patients.

These findings suggest that the MYTHIC trial regimen provides a promising precision medicine approach for a high-need population. By achieving high response rates and significant tumor shrinkage in platinum-resistant and CCNE1-amplified tumors, this therapy may address a critical gap in the management of advanced ovarian cancer.

Additionally, the FDA has granted fast track designation to lunresertib plus zedoresertib as a treatment for adults with CCNE1-amplified or FBXW7/PPP2R1A-deleterious platinum-resistant/refractory ovarian cancer.²

Transcript:

When we looked, specifically, at patients with the [platinum]-resistant/refractory ovarian cancer, we showed that at all dose levels, the overall response [rate] was 37.5%. When we look at patients treated at the potential recommended phase 2 dose, the overall response [rate] was up at 50%. Importantly, 80% of these patients experienced tumor shrinkage. We observed durable responses; at least 37% of patients have been on treatment for greater than 16 weeks. Importantly, as well, 3 additional partial responses have been observed since the data cutoff of [March 25th, 2026]. Interestingly, when we then limit the population to just patients with resistant-refractory CCNE1-amplified ovarian cancer, the actual overall response [rate] improves, of 19 patients, to 42.1%, and the overall response [rate] at the potential RP2D increases to 60%.

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. Presented at the 2026 AACR Annual Meeting; 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 April 30, 2026. https://tinyurl.com/ycx4r5nv