FDA Approves Gedatolisib Plus Fulvestrant for HR-Positive, HER2-Negative Metastatic Breast Cancer

Clinical Summary: 

• The FDA approved gedatolisib based on findings from the phase 3 VIKTORIA-1 trial, which enrolled adults with HR-positive, HER2-negative locally advanced or metastatic breast cancer without a PIK3CA mutation whose disease had progressed following at least one prior line of endocrine therapy in the metastatic setting.
• Gedatolisib combined with fulvestrant, with or without palbociclib, significantly improved progression-free survival compared with fulvestrant alone. Objective response rates and duration of response also improved, while overall survival data remain immature.
• This approval introduces a new PI3K/mTOR-targeted treatment option for patients with PIK3CA wild-type HR-positive, HER2-negative metastatic breast cancer following endocrine therapy progression.

On July 14, 2026, the US Food and Drug Administration (FDA) approved gedatolisib (Revtorpyk; Celcuity Inc.) in combination with fulvestrant, with or without palbociclib, for patients with HR-positive, HER2-negative locally advanced or metastatic breast cancer without a PIK3CA mutation whose disease has progressed following at least one prior line of endocrine therapy in the metastatic setting. This approval was supported by findings from the phase 3 VIKTORIA-1 trial.

In this multicenter, open-label study, 392 patients were randomized 1:1:1 to receive gedatolisib plus fulvestrant and palbociclib, gedatolisib plus fulvestrant, or fulvestrant alone until disease progression or unacceptable toxicity. The primary efficacy end point was progression-free survival (PFS), as assessed by blinded independent central review. Secondary end points included overall survival (OS), objective response rate (ORR), and duration of response.

At analysis, gedatolisib plus fulvestrant and palbociclib significantly improved PFS compared with fulvestrant alone, with a median PFS of 9.3 months versus 2 months, respectively (hazard ratio [HR], 0.24; 95% confidence interval [CI], 0.17 to 0.35; P < .0001). Gedatolisib plus fulvestrant also significantly prolonged PFS compared with fulvestrant alone, with a median PFS of 7.4 months versus 2 months (HR, 0.33; 95% CI, 0.24 to 0.48; P < .0001).

Among patients with measurable disease, the ORR was 32% with gedatolisib plus fulvestrant and palbociclib, 28% with gedatolisib plus fulvestrant, and 1% with fulvestrant alone. Median duration of response was 17.5 months, 12 months, and not estimable, respectively.

At the time of the PFS analysis, OS data were immature, with approximately 25% of patients in the overall study population having died.

The recommended dose of gedatolisib is 180 mg administered as a 30-minute intravenous infusion once weekly on days 1, 8, and 15 of each 28-day cycle in combination with fulvestrant, with or without palbociclib, until disease progression or unacceptable toxicity.

The prescribing information includes warnings and precautions for stomatitis, dermatologic adverse reactions, hyperglycemia, and embryo-fetal toxicity.

Source: 

US Food and Drug Administration. FDA approves gedatolisib with fulvestrant, with or without palbociclib, for HR-positive, HER2-negative locally advanced or metastatic breast cancer. Accessed on July 14, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-gedatolisib-fulvestrant-or-without-palbociclib-hr-positive-her2-negative-locally