Gedatolisib NDA for HR+ PIK3CA Wild-Type Advanced Breast Cancer Has Been Submitted to the FDA

A new drug application (NDA) seeking the approval of gedatolisib (PF-05212384) for the treatment of patients with hormone receptor–positive, HER2-negative advanced breast cancer has been submitted to the FDA for review, according to an announcement from Celcuity, Inc., the drug developer.1

The NDA is supported by data from the PIK3CA wild-type cohort of the phase 3 VIKTORIA-1 trial (NCT05501886) in which the combination of gedatolisib plus fulvestrant (Faslodex) and palbociclib (Ibrance; n = 131) reduced the risk of disease progression or death by 76% vs fulvestrant alone (n = 131).2,3 The median progression-free survival with the triplet regimen was 9.3 months (95% CI, 7.2-16.6) vs just 2.0 months (95% CI, 1.8-2.3) with fulvestrant alone (HR, 0.24; 95% CI, 0.17-0.35; P < .0001). Gedatolisib plus fulvestrant (n = 130) also led to a 67% reduction in the risk of disease progression or death vs fulvestrant alone. The median PFS with the respective approaches was 7.4 months (95% CI, 5.5-9.9) and 2.0 months (95% CI, 1.8-2.3; HR, 0.33; 95% CI, 0.24-0.48; P < .0001).

“This NDA submission is an important milestone, and it brings gedatolisib one step closer to becoming available for patients with [hormone receptor]–positive/HER2-negative advanced breast cancer,” Brian Sullivan, chief executive officer and co-founder of Celcuity, stated in a news release.1 “We look forward to working with the FDA during the NDA review process. We believe the unprecedented efficacy results and overall safety profile of the gedatolisib regimens are potentially practice changing for patients with [hormone receptor]–positive/HER2-negative advanced breast cancer.”

What was the study design for the PIK3CA wild-type cohort of VIKTORIA-1?

This cohort of the global, open-label, phase 3 study included pre- and postmenopausal women and women with hormone receptor–positive, HER2-negative, PIK3CA wild-type advanced breast cancer who experienced disease progression during or following treatment with a CDK4/6 inhibitor plus an aromatase inhibitor and had measurable disease by RECIST v1.1 criteria.2 Patients could have previously received up to 2 lines of endocrine therapy for advanced disease, but they could not have prior exposure to an mTOR inhibitor, a PI3K inhibitor, an AKT inhibitor, or chemotherapy.

Study participants (n = 392) were randomly assigned 1:1:1 to receive the gedatolisib triplet (arm A), the gedatolisib doublet (arm B), or single-agent fulvestrant (arm C). Patients received gedatolisib intravenously (IV) at a once-weekly dose of 180 mg 3-weeks-on and 3-weeks-off on days 1, 8, and 15, palbociclib at a daily dose of 125 mg as part of a 21-days-on and 7-days-off schedule, and fulvestrant at 500 mg for days 1 and 15 of cycle 1 and then every 4 weeks. Notably, upon disease progression, patients on arm C had the option to crossover to arms A or B.

The primary end points of the trial were PFS by blinded independent central review with regard to arm A vs arm C and arm B vs arm C.

What additional efficacy data were reported with gedatolisib?

Although the data, which were shared during the 2025 ESMO Congress, were immature at the data cutoff date of May 30, 2025, with only 48% of protocol-specified events reported, a favorable overall survival (OS) trend was observed for the gedatolisib combinations. The median OS with single-agent fulvestrant was 18.5 months (95% CI, 15.8-not estimable [NE]) vs 23.7 months (95% CI, 21.4-NE) with the triplet (HR, 0.69; 95% CI, 0.43-1.12; P = .1328) and not reached (NR; 95% CI, NR-NR) with the doublet (HR, 0.74; 95% CI, 0.46-1.19; P = .2122).

Moreover, the triplet regimen elicited an ORR of 31.5%, which was comprised of 1 complete response and 38 partial responses (PRs); 67 patients had stable disease (SD) and 17 patients had progressive disease (PD). The clinical benefit rate (CBR) was 50%, the disease control rate (DCR) was 85.5%, and the median duration of response (DOR) was 17.5 months (95% CI, 8.8-NE). With the doublet, the ORR was 28.3%, which was comprised of 32 PRs; 55 patients had SD and 26 experienced PD. The CBR was 48.7%, the DCR was 77.0%, and the median DOR was 12.0 months (95% CI, 8.1-NE). Single-agent fulvestrant induced an ORR of 1.0%, which included 1 PR; 40 patients had SD and 62 had PD. The CBR and DCR were 11.4% and 39.0%, respectively, and the median DOR was NR.

What was learned about the toxicity profile of the gedatolisib combinations in this population?

The gedatolisib regimens were well tolerated overall, with no new safety signals reported. Any-grade treatment-related adverse effects (TRAEs) reported in the triplet and doublet arms included stomatitis (69.2%; 56.9%), rash (27.7%; 32.3%), diarrhea (16.9%; 12.3%), and hyperglycemia (9.2%; 11.5%). TRAEs led to discontinuation for 3 patients who received the triplet and 4 patients who were given the doublet.

What is the significance of the VIKTORIA-1 data?

In an exclusive interview4 with OncLive®, Sara A. Hurvitz, MD, FACP, expanded on the efficacy and safety data from VIKTORIA-1:5 “These data were impressive, even for patients with very endocrine-resistant breast cancer, where the triplet seemed particularly [effective].”

Hurvitz is a medical oncologist, senior vice president, director of and a professor in the Clinical Research Division, the Smith Family Endowed Chair in Women’s Health, and an affiliate investigator in the Translational Science and Therapeutics Division at Fred Hutchinson Cancer Center in Seattle, Washington. She is also a professor in and head of the Division of Hematology and Oncology in the Department of Medicine at the University of Washington.

In another exclusive interview with OncLive, Kelly E. McCann, MD, PhD, also commented on the clinical implications of the findings from VIKTORIA-1:6 “VIKTORIA-1 is an important trial because gedatolisib is a PI3K and mTOR inhibitor. It hits both of those in the same pathway. mTOR inhibition is also an effective way to target the PI3K pathway, [regardless of] whether a patient has a PI3K or AKT mutation. This is an incredibly promising drug.”

Previously, gedatolisib has been awarded breakthrough therapy designation and fast track designation from the regulatory agency; these decisions were supported by preliminary clinical findings.1

References

1. Celcuity announces completion of submission of its new drug application to the US FDA for gedatolisib in HR+/HER2-/PIK3CA wild-type advanced breast cancer. News release. Celcuity, Inc. November 17, 2025. Accessed November 17, 2025. https://www.globenewswire.com/news-release/2025/11/17/3189580/0/en/Celcuity-Announces-Completion-of-Submission-of-Its-New-Drug-Application-to-the-U-S-FDA-for-Gedatolisib-in-HR-HER2-PIK3CA-Wild-Type-Advanced-Breast-Cancer.html
2. VIKTORIA-1 pivotal phase 3 topline results from PIK3CA wild-type cohort. Celcuity, Inc. July 28, 2025. Accessed November 17, 2025. https://ir.celcuity.com/wp-content/uploads/2025/07/Celcuity-Phase-3-VIKTORIA-1-Topline-Results.pdf
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.
4. Hurvitz SA. Dr Hurvitz on data with gedatolisib-based regimens in PIK3CA wild-type HR+/HER2-negative breast cancer. OncLive.com. October 30, 2025. Accessed November 17, 2025. https://www.onclive.com/view/dr-hurvitz-on-data-with-gedatolisib-based-regimens-in-pik3ca-wild-type-hr-her2-negative-breast-cancer
5. Wahner A. Gedatolisib-based regimens may advance PIK3CA wild-type metastatic breast cancer: Q&A with Sara A. Hurvitz, MD, FACP. OncLive.com. October 27, 2025. Accessed November 17, 2025. https://www.onclive.com/view/gedatolisib-based-regimens-may-advance-pik3ca-wild-type-metastatic-breast-cancer-care
6. McCann KE. Dr McCann on the potential clinical utility of gedatolisib in advanced breast cancer. OncLive.com. October 31, 2025. Accessed November 17, 2025. https://www.onclive.com/view/dr-mccann-on-the-potential-clinical-utility-of-gedatolisib-in-advanced-breast-cancer