The FDA has accepted a supplemental new drug application (sNDA) for gedatolisib (Revtorpyk) for adults with hormone receptor–positive, HER2-negative locally advanced or metastatic breast cancer harboring a PIK3CA mutation whose disease progressed on at least one line of endocrine therapy in the metastatic setting.¹ The agency set a Prescription Drug User Fee Act (PDUFA) target action date of June 25, 2027.

Gedatolisib is a kinase inhibitor of class I PI3K isoforms and mTORC1 and mTORC2. The submission is supported by the PIK3CA-mutant cohort of the phase 3 VIKTORIA-1 trial (NCT05501886), a randomized, open-label study of gedatolisib plus fulvestrant (Faslodex), with or without palbociclib (Ibrance), after progression on a CDK4/6 inhibitor plus an aromatase inhibitor.¹˒² The primary end point was progression-free survival (PFS) by blinded independent central review.²

Hormone receptor–positive/HER2-negative disease is the most common breast cancer subtype, accounting for about 70% of cases, and roughly 40% of these tumors harbor PIK3CA mutations.¹ If approved, gedatolisib would be available as second-line therapy regardless of PIK3CA status.

“It's very exciting to think about having a regimen with a therapeutic index this much better, not only because of its efficacy but because of its tolerability. This is something I would want to offer my patients, and I think it also gives them real hope,” said Sara Hurvitz, MD, senior vice president and director of the Clinical Research Division, professor in the Clinical Research Division, and Smith Family Endowed Chair in Women’s Health at Fred Hutch Cancer Center, in an interview with Targeted Onc^TM.

Prior Approval in PIK3CA Wild-Type Disease

On July 14, 2026, the FDA approved gedatolisib with fulvestrant, with or without palbociclib, for adults with hormone receptor–positive/HER2-negative locally advanced or metastatic breast cancer without a detected PIK3CA mutation after progression on at least 1 line of endocrine therapy.³˒⁴ In the wild-type cohort of VIKTORIA-1, median PFS was 9.3 months with the gedatolisib, fulvestrant, and palbociclib triplet vs 2.0 months with fulvestrant alone, a 76% reduction in the risk of progression or death, and 7.4 months with the gedatolisib-fulvestrant doublet, a 67% reduction.³˒⁴

Gedatolisib previously received breakthrough therapy and fast track designations.¹

VIKTORIA-1 PIK3CA-Mutant Cohort Findings

The mutant cohort randomly assigned 350 patients with confirmed PIK3CA mutations 3:3:1 to the gedatolisib triplet, alpelisib (Piqray) plus fulvestrant, or the gedatolisib doublet.⁵ Median PFS was 11.1 months with the triplet vs 5.6 months with alpelisib plus fulvestrant (HR, 0.50; 95% CI, 0.37-0.68; P < .0001). With the doublet, median PFS was 11.3 months vs 5.6 months (HR, 0.51; 95% CI, 0.33-0.79; descriptive P = .0013). Objective response rates were 48.9% with the triplet, 35.7% with the doublet, and 26.0% with alpelisib plus fulvestrant. Median duration of response was 15.7 months, 24.2 months, and 7.5 months, respectively. Overall survival data were immature at the time of analysis, and no overall survival values or hazard ratios were reported. The doublet comparison was descriptive, and the doublet arm was smaller because of the 3:3:1 randomization.

Watch: Sara Hurvitz, MD, discusses the findings from the PIK3CA-mutant cohort of VIKTORIA-1.

Safety Profile

Treatment discontinuation due to treatment-related adverse events (TRAEs) occurred in 2.6% of patients receiving the triplet, 3.8% receiving the doublet, and 7.1% receiving alpelisib plus fulvestrant. Grade 3 or higher TRAEs differed by regimen: neutropenia occurred in 58.8%, 0%, and 0.7%; stomatitis in 16.3%, 5.8%, and 5.3%; rash in 6.5%, 5.8%, and 15.1%; and hyperglycemia in 2.6%, 0%, and 14.5%, respectively. One grade 5 TRAE occurred in the triplet arm and was related to palbociclib; none occurred in the doublet arm, and two occurred with alpelisib plus fulvestrant.

The prescribing information for the approved indication carries warnings and precautions for stomatitis, dermatologic adverse reactions, hyperglycemia, and embryo-fetal toxicity.³ Stomatitis occurred in 72% of patients receiving gedatolisib, fulvestrant, and palbociclib (22% grade 3) and in 58% receiving gedatolisib plus fulvestrant (12% grade 3).¹

Clinical Development Programs

The phase 3 VIKTORIA-2 trial (NCT06757634) comprises 2 first-line studies: study 1 evaluates gedatolisib plus palbociclib and fulvestrant in endocrine-resistant disease, and study 2 evaluates gedatolisib plus palbociclib and letrozole in endocrine-sensitive disease.^1,6 Gedatolisib is also being evaluated with darolutamide (Nubeqa) in metastatic castration-resistant prostate cancer in the phase 1b/2 CELC-G-201 study (NCT06190899).^1,7

FAQs

What did the FDA accept for gedatolisib (Revtorpyk)?

The FDA accepted a supplemental new drug application (sNDA) for gedatolisib in adults with hormone receptor (HR)–positive, HER2-negative locally advanced or metastatic breast cancer harboring a PIK3CA mutation. The application covers patients whose disease progressed on at least one line of endocrine therapy in the metastatic setting.

When will the FDA make a decision?

The FDA set a Prescription Drug User Fee Act (PDUFA) target action date of June 25, 2027.

What data support the application?

The submission is based on the PIK3CA-mutant cohort of the phase 3 VIKTORIA-1 trial (NCT05501886), a randomized, open-label study of gedatolisib plus fulvestrant, with or without palbociclib.

How did gedatolisib perform vs alpelisib in the PIK3CA-mutant cohort?

Median progression-free survival was 11.1 months with the gedatolisib, fulvestrant, and palbociclib triplet vs 5.6 months with alpelisib plus fulvestrant (HR, 0.50; 95% CI, 0.37-0.68; P < .0001). The gedatolisib-fulvestrant doublet reached 11.3 months (HR, 0.51; 95% CI, 0.33-0.79; descriptive P = .0013). Overall survival data were immature at the time of analysis.

What safety findings were reported in the mutant cohort?

Discontinuation due to treatment-related adverse events occurred in 2.6% of patients receiving the triplet, 3.8% receiving the doublet, and 7.1% receiving alpelisib plus fulvestrant. Grade 3 or higher neutropenia occurred in 58.8% of patients receiving the triplet, and grade 3 or higher stomatitis occurred in 16.3%.

Is gedatolisib already approved?

Yes, in PIK3CA wild-type disease. On July 14, 2026, the FDA approved gedatolisib with fulvestrant, with or without palbociclib, for adults with HR+/HER2– locally advanced or metastatic breast cancer without a detected PIK3CA mutation after progression on at least 1 line of endocrine therapy.

What would approval of the sNDA mean?

If approved, gedatolisib would be available as second-line therapy regardless of PIK3CA status.

What other gedatolisib studies are underway?

The phase 3 VIKTORIA-2 trial (NCT06757634) is evaluating gedatolisib in the first-line setting. The phase 1b/2 CELC-G-201 study (NCT06190899) is evaluating gedatolisib plus darolutamide in metastatic castration-resistant prostate cancer.

REFERENCES

1. Celcuity announces FDA acceptance of sNDA for REVTORPYK (gedatolisib) in PIK3CA mutant HR+/HER2- locally advanced or metastatic breast cancer. News release. Celcuity Inc. November 9, 2026. Accessed November 9, 2026. https://tinyurl.com/5y6wavu9

2. Gedatolisib plus fulvestrant with or without palbociclib vs standard-of-care for the treatment of patients with advanced or metastatic HR+/HER2- breast cancer (VIKTORIA-1). ClinicalTrials.gov. Updated February 10, 2026. Accessed November 9, 2026. https://clinicaltrials.gov/study/NCT05501886

3. 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 November 9, 2026. https://tinyurl.com/3bc988ps

4. Celcuity announces FDA approval of REVTORPYK (gedatolisib) for the treatment of HR+/HER2-, PIK3CA wild-type locally advanced or metastatic breast cancer. News release. Celcuity Inc. July 14, 2026. Accessed November 9, 2026. https://tinyurl.com/4bnu7mce

5. Celcuity’s gedatolisib combination regimens doubled the likelihood of survival without disease progression or death compared to alpelisib plus fulvestrant in the PIK3CA mutant cohort of the pivotal phase 3 VIKTORIA-1 Trial in patients with HR+/HER2- advanced breast cancer. News release. Celcuity Inc. June 2, 2026. Accessed November 9, 2026. https://www.celcuity.com/?p=3228

6. VIKTORIA-2: a randomized, open-label, phase 3 study evaluating efficacy and safety of gedatolisib with endocrine therapy and palbociclib vs endocrine therapy and ribociclib as first-line treatment in patients with HR-positive and HER2-negative advanced breast cancer. ClinicalTrials.gov. Updated October 9, 2026. Accessed November 9, 2026. https://clinicaltrials.gov/study/NCT06757634

7. A phase 1/2, open-label, randomized, dose finding and dose expansion study of gedatolisib in combination with darolutamide in metastatic castration-resistant prostate cancer (mCRPC). ClinicalTrials.gov. Updated April 13, 2026. Accessed November 9, 2026. https://clinicaltrials.gov/study/NCT06190899