PIKTOR Plus Paclitaxel Yields Responses in Pretreated PAM-Mutated Endometrial Cancer

PIKTOR, an all-oral combination of serabelisib and sapanisertib, plus paclitaxel yielded a confirmed objective response rate (ORR) of 33% in patients with previously treated advanced endometrioid endometrial cancer harboring a PI3K/AKT/mTOR (PAM) pathway mutation in the phase 2 PIK-201 trial (NCT06463028), according to a news release from the developer, Faeth Therapeutics.¹

What were the preliminary efficacy results from PIK-201?

As of an October 30, 2026, data cutoff, 36 of the 42 treated patients were evaluable for efficacy. The confirmed ORR was 33% (n = 12/36), and the unconfirmed ORR was 36% (n = 13/36). The disease control rate was 83% (n = 30/36). Among 16 patients with PIK3CA-mutant disease, the confirmed ORR was 44% (n = 7/16).

In all 42 treated patients, the preliminary Kaplan-Meier median progression-free survival (PFS) was 7.4 months (95% CI, 5.3-not reached), and the 6-month PFS rate was 62% (95% CI, 43%-75%). Nine of the 12 confirmed responders remained on treatment, as did 7 patients with a best response of stable disease; one patient converted from stable disease to a partial response after 20 months. A total of 16 patients remained on treatment at the cutoff.

“We need more treatment options for patients whose advanced endometrial cancer has progressed after platinum chemotherapy and immunotherapy,” stated David Starks, MD, MPH, a PIK-201 and GOG Foundation principal investigator and gynecologic oncologist at Avera Cancer Institute.¹ “I believe the response and progression-free survival data reported for PIKTOR with paclitaxel give physicians a reason to follow it closely. I am excited by the potential that this treatment could have for my patients.”

What safety findings were reported with PIKTOR plus paclitaxel?

As of an October 23, 2026, cutoff, 64% of the 42 patients had a treatment-related adverse effect (TRAE) of grade 3 or higher. Neutropenia was the most frequent grade 3 or higher TRAE (26%; any grade, 36%). Hyperglycemia occurred in 12% of patients (5 of 42), with 1 patient (2%) experiencing a grade 3 event. Stomatitis occurred in 21% of patients, with 1 patient (2%) experiencing a grade 3 event, and steroid mouthwash prophylaxis was not used.

Two patients (5%) discontinued treatment because of TRAEs (headache and dizziness), and no treatment-related deaths occurred.

What was the design of the PIK-201 trial?

PIK-201, also known as GOG-3111, is an ongoing, open-label, single-arm phase 2 trial conducted with The GOG Foundation.² Patients were those with advanced endometrioid endometrial cancer with a PAM pathway mutation who had received at least 1 but no more than 4 prior systemic therapies, including platinum-based chemotherapy and a checkpoint inhibitor. The median number of prior lines of therapy was 2 (range, 1-4), and 36% of patients (n = 15) had received at least 3. All patients had received prior taxane chemotherapy, 98% had received prior immunotherapy, 76% had distant metastases (including liver and lung), and 48% had diabetes or prediabetes at baseline.

The primary end point of the trial was ORR, with secondary end points including PFS, 6-month PFS, overall survival, clinical benefit rate, and safety.

What are the next steps for PIKTOR?

PIKTOR is investigational, and no regulatory authority has approved it. Faeth plans to advance PIKTOR toward a phase 3 trial, subject to regulatory alignment. The release noted that the results may change with scan confirmation and continued follow-up, and that a single-arm study cannot establish comparative efficacy or safety.

“We believe these data support the multi-nodal PAM targeting hypothesis, whereby more complete inhibition of the pathway may drive durable responses and extend [PFS] without the safety limitations of single-node inhibitors,” added Anand Parikh, co-founder and chief executive officer of Faeth.¹ “Endometrial cancer has among the highest rates of PI3K pathway alterations of any cancer, yet no drug that targets the pathway is approved to treat it.”

References

1. Faeth reports positive preliminary phase 2 topline results from the PIK-201 trial evaluating PIKTOR in combination with paclitaxel in patients with advanced endometrial cancer. News release. Faeth Therapeutics. November 9, 2026. Accessed November 9, 2026. https://tinyurl.com/4ebn38m5
2. 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 November 9, 2026. https://tinyurl.com/4rc8hx57