When Timothy Yap and his team at the University of Texas MD Anderson Cancer Center started the MYTHIC trial, they were hunting for a smarter way to attack cancers that have long frustrated oncologists—tumors with specific genetic alterations that make them particularly hard to treat. Four years later, their first-in-class drug combination is showing results that have earned it something rare in cancer research: expedited FDA review.
The treatment pairs two novel inhibitors—zedoresertib and lunresertib—working in concert against cancer cells that carry CCNE1 amplification or mutations in the FBXW7 and PPP2R1A genes. These genetic quirks show up most often in ovarian cancer, but also appear in colorectal, pancreatic, and breast cancers. For patients whose tumors carry these alterations, standard treatments often stop working, leaving few options.
The approach is elegant in its precision. Zedoresertib, developed by Debiopharm, blocks the WEE1 kinase—a protein that acts as a checkpoint protecting damaged cancer cells until they can repair themselves before dividing. Lunresertib, from Repare Therapeutics and also licensed to Debiopharm, targets a different cell cycle regulator called PKMYT1. Together, they push already-stressed cancer cells into premature division, causing them to die. It's what scientists call synthetic lethality: two drugs that are each manageable alone but devastating to tumors when combined.
The Phase I trial enrolled 62 patients with advanced, treatment-resistant solid tumors. Among the 54 whose results could be evaluated, the overall disease control rate reached 68.5 percent—meaning their cancers either shrank or held steady. Among the subset with ovarian cancers harboring the targeted genetic alterations, the numbers were even more striking: 80 percent showed consistent tumor shrinkage, with durable responses continuing in many patients. Ten patients, or 37 percent, remained on treatment for more than 16 weeks; five patients stayed on therapy beyond 32 weeks.
The molecular response rate—which measures how thoroughly the treatment hit its biological targets—climbed to 67 percent in ovarian cancer patients, compared to 47 percent across all participants. Side effects remained largely mild, manifesting as manageable nausea, vomiting, or fatigue.
Based on these findings, the FDA granted the combination Fast Track Designation specifically for ovarian cancer patients carrying these genetic profiles. Yap, who leads clinical development at MD Anderson's Therapeutics Discovery division, noted that these patients represent an area of significant unmet need—and that the synergy they saw in laboratory studies is now translating into real benefit.
The results, presented at the 2026 American Association for Cancer Research Annual Meeting, represent an early but meaningful milestone. Phase I trials are designed primarily to test safety, yet the antitumor activity observed here has given researchers enough signal to push forward with urgency. Next steps will involve expanding the patient groups and confirming optimal dosing. For a disease where recurrence rates remain high and treatment options thin, this synthetic lethal strategy offers something patients and oncologists rarely get to say: a new path forward.