REVTORPYK (gedatolisib) is indicated for use in combination with fulvestrant, with or without palbociclib, for adult patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, locally advanced or metastatic breast cancer without a detected PIK3CA mutation.
Developed by Celcuity, the drug is intended for use after disease progression on, or following, at least one line of endocrine therapy in the metastatic setting.
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The US Food and Drug Administration (FDA) approved the drug in July 2026, and Celcuity plans to introduce the product commercially late in the third quarter of 2026 (Q3 2026).
REVTORPYK is provided as a sterile, white to off-white lyophilised powder for injection, with each single-use vial containing 180mg of gedatolisib, intended for reconstitution followed by further dilution.
The recommended dosing regimen for gedatolisib is 180mg administered as a 30‑minute intravenous infusion once weekly on days 1, 8 and 15 of a 28‑day cycle, in combination with fulvestrant, with or without palbociclib, and continued until disease progression or the occurrence of unacceptable toxicity.
Celcuity is planning to file a supplemental New Drug Application (sNDA) with the FDA in Q3 2026 for REVTORPYK in HR+/HER2−, PIK3CA-mutant, locally advanced or metastatic breast cancer in patients who have received at least one prior endocrine-based regimen.
After submitting the sNDA, the company also plans to pursue marketing authorisation for gedatolisib with regulators in other territories.
HR+/HER2- breast cancer causes and symptoms
Breast cancer is among the most frequently diagnosed malignancies in women. It arises when abnormal cells in breast tissue proliferate and form a tumour. Around 80% of breast cancer cases are invasive, indicating that the tumour has the potential to extend beyond the breast to other parts of the body.
The disease occurs most often in women aged 50 years and older, although younger women may also be affected. Men can develop breast cancer as well, albeit far less commonly.
Female breast cancer is commonly categorised into four principal biological subtypes, HR+/HER2−, HR−/HER2−, HR+/HER2+, and HR−/HER2+.
HR+/HER2− disease is the predominant subtype, representing around 70% of all breast cancer diagnoses. Within this group, approximately 60% of cases are PIK3CA wild-type.
A palpable lump in the breast or underarm, redness or flaking of the skin in the nipple region, and localised breast pain are among the commonly reported symptoms of breast cancer.
REVTORPYK mechanism of action
Gedatolisib is a kinase inhibitor that targets class I Phosphoinositide 3-kinase isoforms (α, β, δ, γ) and the mechanistic target of rapamycin (mTOR) complexes, mTORC1 and mTORC2, leading to downstream inhibition of multiple signalling effectors, including Protein kinase B, also known as AKT.
In oestrogen receptor (ER)-positive breast cancer cell lines and xenograft models with either wild-type or mutant PIK3CA, gedatolisib demonstrated pro-apoptotic and anti-proliferative activity in vitro and reduced tumour growth in vivo.
In a human ER-positive breast cancer xenograft model with a PIK3CA mutation, the combination of gedatolisib, palbociclib and fulvestrant produced greater inhibition of tumour growth than any single agent or doublet combination.
Clinical trials on REVTORPYK
The FDA approved REVTORPYK based on safety and efficacy data from the PIK3CA wild-type cohort of the Phase III VIKTORIA-1 trial (NCT05501886).
VIKTORIA-1 is an open-label, global, randomised study that enrolled 392 adults with locally advanced or metastatic HR‑positive, HER2‑negative breast cancer whose disease had progressed during or after prior treatment with a CDK4/6 inhibitor and an aromatase inhibitor.
Participants were randomised (1:1:1) to one of three treatment arms.
In arm A, 131 patients were administered with REVTORPYK 180mg intravenously once weekly on days 1, 8 and 15 of each 28‑day cycle, followed by one week off, in combination with fulvestrant 500mg given intramuscularly on days 1 and 15 of cycle 1 and then on day 1 of each subsequent 28‑day cycle, plus palbociclib 125mg taken orally once daily for 21 days followed by seven days off in each 28‑day cycle.
Arm B included 130 patients who were administered REVTORPYK 180mg intravenously on the same three-week on, one-week off schedule, combined with fulvestrant 500mg.
In arm C, 131 patients were administered fulvestrant 500mg intramuscularly on days 1 and 15 of cycle 1 and then on day 1 of each subsequent 28‑day cycle.
The primary efficacy endpoint was progression-free survival (PFS), assessed by blinded independent central review using Response Evaluation Criteria in Solid Tumors version 1.1, comparing arm A with arm C and arm B with arm C. Secondary efficacy endpoints included overall survival, objective response rate (ORR) and duration of response (DoR).
In the comparison of the triplet regimen or arm A versus arm C, the median PFS was 9.3 months and two months, respectively, corresponding to a 7.3‑month difference. The ORR for arm A was 32% compared with 1% for arm C. Median DoR for arm A was 17.5 months, while median DoR for arm C could not be estimated as only one objective response was observed.
For the doublet regimen or arm B versus arm C, median PFS was 7.4 months and two months, respectively, a difference of 5.4 months. The ORR for the doublet was 28%, with a median DoR of 12 months.
In the PIK3CA wild-type population evaluated in VIKTORIA‑1, the combination of REVTORPYK with palbociclib and fulvestrant reduced the risk of disease progression or death by 76%, and the combination of REVTORPYK with fulvestrant reduced this risk by 67%, each compared with fulvestrant alone.
The most adverse reactions during the clinical trial were reductions in white blood cell counts, stomatitis, nausea, vomiting and diarrhoea.
Additional clinical trials
REVTORPYK continues to be assessed in the Phase III VIKTORIA-2 clinical trial, comprising two distinct studies (Study 1 and Study 2) conducted in separate cohorts of patients with locally advanced or metastatic breast cancer who have not previously received therapy in the advanced-disease setting.
Study 1 is assessing gedatolisib in combination with palbociclib and fulvestrant as a first-line option for individuals with endocrine-resistant HR+/HER2- locally advanced or metastatic breast cancer. Study 2 is investigating gedatolisib alongside palbociclib and letrozole as initial therapy for those with endocrine-sensitive HR+/HER2- locally advanced or metastatic breast cancer.
In addition, CELC-G-201, an ongoing Phase I/II study, is examining gedatolisib in combination with darolutamide in patients with metastatic castration-resistant prostate cancer.
