FDA Grants Fast Track Designation to Sapanisertib and Serabelisib Plus Paclitaxel in Advanced Endometrial Cancer

The FDA has granted fast track designation to the investigational, all-oral combination of sapanisertib and serabelisib (PIKTOR) plus paclitaxel for the treatment of patients with advanced or recurrent endometrial cancer whose tumors harbor a PI3K/AKT/mTOR pathway alteration and who have previously received platinum-based chemotherapy and an immune checkpoint inhibitor (ICI).¹

The combination is being evaluated in the ongoing phase 2 FTH-PIK-201/GOG-3111 trial (NCT06463028), with top-line data anticipated by the end of 2026.^1,2

“Fast track designation for [sapanisertib plus serabelisib] 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 [sapanisertib plus serabelisib’s] multi-node approach to the PI3K/AKT/mTOR pathway is well suited to this population, as our preclinical data suggest that [sapanisertib plus serabelisib] can resensitize patients to chemotherapy.”

What is the mechanism of action of sapanisertib plus serabelisib?

Serabelisib is a selective PI3Kα inhibitor, and sapanisertib is an mTORC1/mTORC2 inhibitor. The combination is designed to inhibit multiple nodes of the PI3K/AKT/mTOR pathway. Multi-node inhibition of this pathway has resulted in more complete blockade than single-node inhibition in preclinical models.²

How was the FTH-PIK-201 trial designed?

FTH-PIK-201 is a multicenter, open-label, single-arm study evaluating sapanisertib plus serabelisib in combination with paclitaxel in patients at least 18 years with advanced or recurrent endometrial cancer who have a PI3K/AKT/mTOR pathway alteration and who have progressed on prior systemic therapy, including a platinum-based therapy and an ICI, administered either separately or together.²˒³ Patients need to have received between 1 and 4 prior systemic therapies, have at least 1 measurable target lesion per RECIST 1.1 criteria, and have an ECOG performance status of at least 1 at screening.³

Sapanisertib at 3 mg plus serabelisib at 200 mg will be administered orally once daily for 3 days a week with food on days 2 through 4, 9 through 11, 16 through 18, and 23 through 25 of each 28-day cycle.² Weekly paclitaxel will be given at 80 mg/m² intravenously on days 1, 8, and 15 of each cycle.

The primary end point of the trial is objective response rate.^2,3 Secondary end points include progression-free survival (PFS), PFS at 6 months, overall survival, clinical benefit rate, duration of response, and safety and tolerability. The trial also includes a substudy evaluating the impact of an insulin-suppressing diet on the tolerability and efficacy of sapanisertib plus serabelisib and paclitaxel.

The combination builds on an earlier signal seen in a phase 1b trial (NCT03154294) investigating paclitaxel plus serabelisib and sapanisertib. In the trial, the triplet produced responses in 4 of 5 patients (3 complete responses and 1 partial response) with advanced/recurrent endometrioid cancer; the fifth patient had a best response of stable disease.⁴

What are the next steps for investigating sapanisertib plus serabelisib?

Beyond endometrial cancer, sapanisertib plus serabelisib is being evaluated in the phase 1b/2 FTH-PIK-101 trial (NCT07558733) in patients with hormone receptor–positive, HER2-negative advanced or metastatic breast cancer.¹ The first patient was dosed in April 2026, and interim data are anticipated in 2027.

The FDA fast track designation adds to prior regulatory activity in endometrial cancer, a setting in which biomarker-defined populations have become a focus of drug development. Notably, in July 2026, selinexor (Xpovio) maintenance therapy did not significantly improve PFS vs placebo in patients with TP53 wild-type advanced or recurrent endometrial cancer in the phase 3 XPORT-EC-042 trial (NCT05611931).⁵

References

1. Faeth Therapeutics announces FDA grant of fast track designation for PIKTOR plus paclitaxel in biomarker-selected advanced endometrial cancer. News release. Faeth Therapeutics. August 17, 2026. Accessed August 17, 2026. https://investors.faeththerapeutics.com/news-releases/news-release-details/faeth-therapeutics-announces-fda-grant-fast-track-designation
2. Westin SN, Slomovitz BM, Konstantinopoulos PA, et al. Sapanisertib and serabelisib (PIKTOR) with paclitaxel and a diet substudy in patients with advanced/recurrent endometrial cancer (GOG-3111). J Clin Oncol. 2025;43(suppl 16):TPS5633. doi:10.1200/JCO.2025.43.16_suppl.TPS5633
3. Sapanisertib and serabelisib (PIKTOR) with paclitaxel and a substudy with an insulin-suppressing diet in patients with advanced/recurrent endometrial cancer. ClinicalTrials.gov. Updated December 24, 2025. Accessed August 17, 2026. https://clinicaltrials.gov/study/NCT06463028
4. Starks DC, Rojas-Espaillat L, Meissner T, et al. 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
5. Karyopharm announces topline results from phase 3 XPORT-EC-042 trial in endometrial cancer. News release. Karyopharm Therapeutics Inc. July 30, 2026. Accessed August 17, 2026. https://www.prnewswire.com/news-releases/karyopharm-announces-topline-results-from-phase-3-xport-ec-042-trial-in-endometrial-cancer-302839314.html