FDA Accepts NDA for Gedatolisib in HR+/HER2–, PIK3CA Wild-Type Breast Cancer

The FDA has accepted a new drug application (NDA) for gedatolisib for the treatment of patients with hormone receptor (HR)–positive, HER2-negative, PIK3CA wild-type advanced breast cancer, according to a press release from Celcuity Inc.¹

The agency granted priority review for the application and assigned a Prescription Drug User Fee Act goal date of July 17, 2026. The submission was processed under the Real-Time Oncology Review program following previous Breakthrough Therapy and Fast Track designations.

“The FDA’s acceptance of our NDA for gedatolisib and the assignment of a PDUFA goal date is a pivotal milestone in our efforts to bring a much-needed new treatment option to patients with HR+/HER2- advanced breast cancer,” Brian Sullivan, chief executive officer and co-founder of Celcuity, said in the press release.¹ “We believe the robust clinical dataset underlying this submission demonstrates the practice-changing potential of gedatolisib. We are looking forward to collaborating with the FDA throughout the review process as we work towards a potential approval and commercial launch.”

VIKTORIA-1 Data

The NDA submission was supported by clinical data from the PIK3CA wild-type cohort of the phase 3 VIKTORIA-1 trial (NCT05501886).² Results demonstrated that the addition of gedatolisib, a multi-target PI3K/AKT/mTOR (PAM) inhibitor, to fulvestrant (Faslodex) with or without palbociclib (Ibrance) led to statistically significant and clinically meaningful improvements in progression-free survival (PFS).

Data presented at the 2025 San Antonio Breast Cancer Symposium (SABCS) revealed among those with a time to progression of longer than 6 months on previous therapy a median progression-free survival (PFS) of 9.9 months (95% CI, 7.2-19.2) in the triplet arm vs 1.9 months (95% CI, 1.8-2.3) in the monotherapy arm (HR, 0.20; 95% CI, 0.13-0.30; P <.0001).² For those receiving the doublet regimen in the same group, the median PFS was 7.6 months (95% CI, 5.5-10.0; HR, 0.25; 95% CI, 0.17-0.37; P <.0001).

If patients had a time to progression of longer than 12 months, the median PFS in the triplet arm was 10.7 months (95% CI, 7.2-19.2) vs 1.9 months (95% CI, 1.8-3.5) in the monotherapy arm (HR, 0.21; 95% CI, 0.15-0.31; P <.0001). The doublet arm had a median PFS of 9.1 months (95% CI, 5.5-13.6; HR, 0.26; 95% CI, 0.18-0.37; P <.0001).

If the time to progression was longer than 18 months, the median PFS in the triplet arm was 12.4 months (95% CI, 7.0-19.3) compared with 1.9 months (95% CI, 1.8-3.5) in the monotherapy arm (HR, 0.17; 95% CI, 0.11-0.28; P <.0001); the median PFS with the gedatolisib doublet was 10.0 months (95% CI, 5.6-not evaluable [NE]; HR, 0.19; 95% CI, 0.12-0.31; P <.0001). For patients with a time to progression of longer than 24 months, the median PFS was 12.4 months (95% CI, 7.4-NE) vs 2.0 months (95% CI, 1.8-3.7), between arms, respectively (HR, 0.26; 95% CI, 0.26-0.28; P <.0001); with the gedatolisib doublet, the median PFS was 13.6 months (95% CI, 7.6-NE; HR, 0.14; 95% CI, 0.08-0.27; P <.0001).

Data presented at the In the primary analysis, the European Society for Medical Oncology (ESMO) Congress 2025showed that gedatolisib-based triplet reduced the risk of disease progression or death by 76% compared with fulvestrant monotherapy (HR, 0.24; 95% CI, 0.17-0.35; P <.0001).³ The median PFS for patients receiving the triplet was 9.3 months (95% CI, 7.2-16.6) vs 2.0 months (95% CI, 1.8-2.3) for those receiving fulvestrant alone. The gedatolisib doublet also demonstrated superior efficacy, reducing the risk of disease progression or death by 67% compared with the control arm (HR, 0.33; 95% CI, 0.24-0.48; P <.0001), with a median PFS of 7.4 months (95% CI, 5.5-9.9).

The objective response rate (ORR) was 31.5% for the triplet and 28.3% for the doublet, compared to 1.0% for fulvestrant monotherapy. The median duration of response for the triplet was 17.5 months (95% CI, 8.8-NE). Interim overall survival (OS) data showed a positive trend favoring the gedatolisib combinations, with an adjusted hazard ratio of 0.69 (95% CI, 0.43-1.12; P = .1328) for the triplet and 0.74 (95% CI, 0.46-1.19; P = .2122) for the doublet.

Trial details

VIKTORIA-1 is an open-label, randomized phase 3 trial that enrolled adults with histologically or cytologically confirmed metastatic or locally advanced breast cancer. Eligible patients had documented estrogen receptor–positive and HER2-negative disease. Participants were required to have experienced radiological disease progression on or after a prior CDK4/6 inhibitor combined with a non-steroidal aromatase inhibitor.

A total of 392 patients with PIK3CA wild-type disease were randomly assigned 1:1:1 to receive one of three regimens:

• Arm A (Triplet): Intravenous gedatolisib 180 mg on days 1, 8, and 15 of a 28-day cycle; oral palbociclib 125 mg daily (3 weeks on, 1 week off); and intramuscular fulvestrant 500 mg.
• Arm B (Doublet): Gedatolisib 180 mg on the same weekly schedule and fulvestrant 500 mg.
• Arm C (Control): Fulvestrant 500 mg monotherapy.

The co-primary end points were PFS as assessed by blinded independent central review. Secondary end points included OS, ORR, duration of response, and safety. Subgroup analyses indicated the triplet may offer higher clinical benefit in pre/perimenopausal patients and those with visceral metastases.

Safety

The safety profiles for the gedatolisib regimens were reported as manageable and consistent with the known profiles of the individual agents. Stomatitis was the most frequently reported adverse event; however, most cases were low-grade and manageable with prophylactic measures. Grade 3 stomatitis occurred in 69.2% of the triplet arm and 56.9% of the doublet arm.

Notably, gedatolisib did not cause clinically relevant hyperglycemia, a common concern with other PI3K pathway inhibitors. Any-grade hyperglycemia occurred in 9.2% of patients in the triplet arm and 11.5% in the doublet arm. Other observed grade 3 events included rash (27.7% triplet; 32.3% doublet) and diarrhea (16.9% triplet; 12.3% doublet).

References

1. Celcuity announces FDA acceptance of new drug application for gedatolisib in HR+/HER2-/PIK3CA wild-type advanced breast cancer. News release. Celcuity. January 20, 2026. Accessed January 20, 2026. https://tinyurl.com/537dthfv
2. Pistilli B, Layman RM, Curigliano G, et al. Gedatolisib, a multitarget PI3K/AKT/mTOR inhibitor, plus fulvestrant with or without palbociclib for second-line treatment of patients with HR+/HER2-/PIK3CA-WT advanced breast cancer: updated results from the randomized, phase 3 VIKTORIA-1 trial. Presented at: 2025 San Antonio Breast Cancer Symposium; December 9-12, 2025; San Antonio, TX. Abstract R47-04.
3. Hurvitz SA, Layman RM, Curigliano G, et al. Gedatolisib plus fulvestrant, with and without palbociclib, vs fulvestrant in patients with HR+/HER2-/PIK3CA wild-type advanced breast cancer: first results from VIKTORIA-1. Presented at: 2025 ESMO Annual Congress; October 17-21, 2025; Berlin, Germany. Abstract LBA17.