sNDA for Gedatolisib Submitted to FDA in PIK3CA-Mutant Breast Cancer

A supplemental new drug application (sNDA) has been submitted to the FDA for gedatolisib (Revtorpyk) in combination with fulvestrant (Faslodex), with or without palbociclib (Ibrance), for adults with hormone receptor (HR)-positive, HER2-negative (HER2–), locally advanced or metastatic breast cancer harboring a PIK3CA mutation who have progressed on at least 1 line of endocrine therapy, according to a press release from Celcuity.¹

If approved, gedatolisib would become the first therapy for PIK3CA-mutant advanced breast cancer to inhibit all class I PI3K isoforms (alpha, beta, delta, gamma) along with both mTOR complexes, mTORC1 and mTORC2. The submission would expand the drug’s label beyond its current indication, which covers patients with HR-positive, HER2-negative disease without a PIK3CA mutation.

“This submission allows us to potentially make [gedatolisib] available to all patients with HR+/HER2– locally advanced or metastatic breast cancer, regardless of PIK3CA mutation status,” Igor Gorbatchevsky, MD, chief medical officer of Celcuity, said in the release.¹ “In the PIK3CA mutant cohort of the VIKTORIA-1 trial, [gedatolisib] demonstrated compelling safety and efficacy results. Pending regulatory approval, we believe [gedatolisib] has the potential to become an important treatment option in this indication.”

VIKTORIA-1 Results

The application is supported by results from the PIK3CA-mutant cohort of the phase 3 VIKTORIA-1 trial (NCT05501886), an open-label, randomized study of gedatolisib-based regimens in adults whose HR+, HER2– advanced breast cancer had progressed after treatment with a CDK4/6 inhibitor plus an aromatase inhibitor.^2,3 Of the 701 patients enrolled in VIKTORIA-1 regardless of PIK3CA status, 350 with confirmed PIK3CA mutations were randomly assigned 3:3:1 to gedatolisib plus fulvestrant and palbociclib (the gedatolisib triplet), alpelisib (Piqray) plus fulvestrant, or gedatolisib plus fulvestrant alone (the gedatolisib doublet).

The gedatolisib triplet reduced the risk of disease progression or death by 50% compared with alpelisib plus fulvestrant (HR, 0.50; 95% CI, 0.37-0.68; P <.0001), with a median progression-free survival (PFS) of 11.1 months vs 5.6 months. The gedatolisib doublet produced a 49% reduction in the risk of progression or death vs alpelisib plus fulvestrant (HR, 0.51; 95% CI, 0.33-0.79; descriptive P = .0013), with a median PFS of 11.3 months vs 5.6 months. Objective response rates were 49% for the triplet, with a median duration of response (DOR) of 15.7 months, and 36% for the doublet, with a median DOR of 24.2 months. Safety findings in the PIK3CA-mutant cohort were generally consistent with those previously reported in the PIK3CA wild-type cohort of VIKTORIA-1.

Gedatolisib FDA Approval

Gedatolisib in combination with fulvestrant, with or without palbociclib, already carries FDA approval for HR-positive, HER2-negative advanced breast cancer without a PIK3CA mutation, granted July 14, 2026, following progression on at least 1 line of endocrine therapy in the metastatic setting.⁴ Previously reported results from the 2025 European Society for Medical Oncology (ESMO) Annual Meeting showed the gedatolisib triplet produced a median PFS of 9.3 months vs 2.0 months with fulvestrant alone (HR, 0.24; 95% CI, 0.17-0.35; P <.0001), and the doublet produced a median PFS of 7.4 months vs 2.0 months (HR, 0.33; 95% CI, 0.24-0.48; P <.0001).⁵

Additionally, the gedatolisib and fulvestrant regimens, with or without palbociclib, earned a preferred Category 1 listing in the NCCN Clinical Practice Guidelines for this population.⁶

“The recent FDA approval of [gedatolisib] marked an important milestone for Celcuity and for patients with PIK3CA wild-type HR+/HER2– advanced breast cancer,” Brian Sullivan, chief executive officer and co-founder of Celcuity, said in the release.¹ “We are deeply committed to expanding the availability of [gedatolisib] to a broader population of patients. We look forward to working collaboratively with the FDA on this application to potentially bring this treatment to patients with PIK3CA mutated locally advanced or metastatic breast cancer.”

Across both VIKTORIA-1 cohorts, gedatolisib’s safety profile included stomatitis, hyperglycemia, and rash. In the PIK3CA wild-type cohort, stomatitis occurred in 72% of patients on the triplet and 58% of those on the doublet, with grade 3 events in 22% and 12% of patients, respectively; a steroid-containing, alcohol-free mouthwash is recommended prophylactically before and during treatment. Rash occurred in 30% of triplet-treated and 40% of doublet-treated patients, and hyperglycemia occurred in 46% and 57%, respectively. The drug also carries an embryo-fetal toxicity warning requiring effective contraception during treatment and for 2 weeks after the final dose.

References

1. Celcuity submits sNDA to FDA for REVTORPYK (gedatolisib) for HR+/HER2-, PIK3CA mutant locally advanced or metastatic breast cancer. News release. Celcuity Inc. August 26, 2026. Accessed August 27, 2026. https://tinyurl.com/yr9yexss

2. Hurvitz SA, Layman RM, Curigliano G, et al. Gedatolisib plus fulvestrant, with & 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.

3. Study of gedatolisib on background therapy for participants with HR+/HER2- advanced or metastatic breast cancer (VIKTORIA-1). ClinicalTrials.gov. Updated February 10, 2026. Accessed August 27, 2026. https://tinyurl.com/2ud67eme

4. FDA approves gedatolisib with fulvestrant, with or without palbociclib, for HR-positive, HER2-negative locally advanced or metastatic breast cancer. FDA. July 14, 2026. Accessed August 27, 2026. https://tinyurl.com/yck3eabf

5. Hurvitz SA, Layman RM, Curigliano G, et al. Gedatolisib Plus Fulvestrant, With & 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.

6. Newly FDA-approved REVTORPYK (gedatolisib) included in the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines for HR+/HER2- locally advanced or metastatic breast cancer. News release. Celcuity Inc. July 30, 2026. Accessed August 27, 2026. https://tinyurl.com/2ma4knfw