FDA Grants Fast Track Designation to Piktor in Endometrial Cancer

The FDA has granted fast track designation to the combination of sapanisertib and serabelisib, known as Piktor, for use in combination with paclitaxel for patients with advanced or recurrent endometrial cancer whose tumors harbor a PI3K/AKT/mTOR pathway alteration and who have progressed after platinum-based chemotherapy and an immune checkpoint inhibitor (ICI), according to Faeth Therapeutics, the regimen's developer.¹

Fast Track status is intended to facilitate the development and expedite the FDA review of therapies for serious conditions with an unmet medical need, and it allows for more frequent interaction with the agency throughout the review process.

Piktor is an investigational, all-oral regimen that pairs serabelisib, a selective inhibitor of the alpha isoform of phosphoinositide 3-kinase (PI3K), with sapanisertib, which inhibits both complexes of the mechanistic target of rapamycin (mTOR), in an approach designed to block multiple points along the PI3K/AKT/mTOR signaling cascade. Faeth notes that this pathway is dysregulated in up to half of all solid tumors, making it one of the most heavily pursued targets in oncology drug development.¹

In the phase 1 trial that first established the regimen's activity (NCT03154294), sapanisertib and serabelisib combined with paclitaxel produced responses in 4 of the 5 evaluable patients with endometrial cancer, including 3 complete responses and 1 partial response, for an overall response rate (ORR) of 80%.² Across the full trial population of 19 heavily pretreated patients with advanced ovarian, endometrial, or breast cancer, the response rate by intention to treat was 37%, rising to 47% among those who completed at least 3 cycles of therapy, with a clinical benefit rate of 73%. Median progression-free survival across the cohort was approximately 11 months, and median overall survival was approximately 17 months.

"Fast track designation for Piktor reflects the significant unmet need in advanced endometrial cancer for patients whose disease has progressed despite platinum-based chemotherapy and an immune checkpoint inhibitor," Anand Parikh, chief executive officer of Faeth Therapeutics, stated in a news release.¹ "We believe Piktor's multi-node approach to the PI3K/AKT/mTOR pathway is well suited to this population as our preclinical data suggests that Piktor can resensitize patients to chemotherapy."

Safety of Piktor

Investigators reported 45 grade 3 or higher adverse events (AEs) across the trial, accounting for 9% of all AEs recorded, most frequently decreased white blood cell counts and non-febrile neutropenia.2 The most common non-laboratory AEs of grade 3 or higher were nausea (6%), fatigue (5%), and mucositis (5%).² Investigators concluded that the combination was tolerable and did not identify new or unexpected toxicities from pairing dual PI3K and mTOR inhibition with paclitaxel.²

Study Design and Patient Characteristics

The phase 1 dose-escalation trial enrolled 19 patients, including 10 with ovarian cancer, 6 with endometrial cancer, and 3 with breast cancer, all of whom were heavily pretreated with a median of more than 4 prior lines of therapy.³ Sapanisertib and serabelisib were administered on days 2 through 4, 9 through 11, 16 through 18, and 23 through 25 of each 28-day cycle, together with paclitaxel on days 1, 8, and 15. The recommended phase 2 dose was established as sapanisertib 3 mg or 4 mg and serabelisib 200 mg on those dosing days, combined with paclitaxel 80 mg/m2 on days 1, 8, and 15 of each cycle.³

Faeth is now evaluating the combination in an ongoing phase 2 trial in this second-line setting, Study FTH-PIK-201, with topline data expected by the end of 2026.¹ The company is separately testing Piktor plus paclitaxel in a phase 1b/2 trial in hormone receptor–positive, HER2-negative advanced breast cancer, Study FTH-PIK-101, for which the first patient was dosed in April 2026 and interim data are anticipated in 2027.¹

References

1. Faeth Therapeutics. Faeth Therapeutics announces FDA grant of Fast Track designation for Piktor plus paclitaxel in biomarker-selected advanced endometrial cancer. News release. Published August 17, 2026. Accessed August 18, 2026. https://tinyurl.com/mrbhxx2p

2. Starks DC, Rojas-Espaillat L, Dey N, et al. Final results of phase 1 evaluation of the safety and clinical activity of sapanisertib in combination with serabelisib and paclitaxel in patients with advanced ovarian, endometrial, or breast cancer. J Clin Oncol. 2021;39(15 suppl):5569. doi: 10.1200/JCO.2021.39.15_suppl.5569

3. Starks DC, Rojas-Espaillat L, Meissner T, Williams CB. Phase I dose escalation study of dual PI3K/mTOR inhibition by sapanisertib and serabelisib in combination with paclitaxel in patients with advanced solid tumors. Gynecol Oncol. 2022;166(3):403-409. doi: 10.1016/j.ygyno.2022.07.005