Revtorpyk (gedatolisib): FDA approval, pivotal trial and safety
Approved
Type
New molecular entity · Intravenous
FDA-approved use
In combination with fulvestran, to treat hormone receptor-positive, human epidermal growth factor receptor 2-negative, locally advanced or metastatic breast cancer without a PIK3CA mutation detected following progression on or after treatment with at least one line of endocrine therapy in the metastatic settingWording from FDA's list of novel approvals.
FDA review
Priority review
Company
Celcuity
Application
NDA 219908
Specialty
Oncology
At a glance
Revtorpyk (gedatolisib) is an intravenous PI3K/mTOR kinase inhibitor approved July 14, 2026, with fulvestrant, with or without palbociclib, for HR-positive, HER2-negative advanced breast cancer without a detected PIK3CA mutation after progression on endocrine therapy. In VIKTORIA-1, median progression-free survival was 9.3 months with the triplet (HR 0.24) and 7.4 months with the doublet (HR 0.33), versus 2.0 months with fulvestrant alone. Stomatitis, rash and hyperglycemia are the main safety concerns.
What it is and how it works
Gedatolisib inhibits all four class I PI3K isoforms and both mTOR complexes, mTORC1 and mTORC2, which reduces downstream signaling including AKT. Oral PI3K or AKT inhibitors used today block narrower targets and are limited to tumors with specific mutations. Gedatolisib is given in tumors without a detected PIK3CA mutation. In preclinical models it showed activity with both wild-type and mutant PIK3CA.
Open-label, randomized, multicenter phase 3 trial with three arms randomized 1:1:1, stratified by visceral metastases, duration of prior therapy and region. Patients in the fulvestrant arm could cross over at progression.
Patients
392 adults with locally advanced or metastatic HR-positive, HER2-negative, PIK3CA wild-type breast cancer who progressed on or after a CDK4/6 inhibitor and an aromatase inhibitor. Median age was 56 years, and 79% had visceral metastases.
Compared with
Fulvestrant alone (n=131). The experimental arms were gedatolisib plus fulvestrant plus palbociclib (n=131) and gedatolisib plus fulvestrant (n=130).
Primary endpoint
Progression-free survival by blinded independent central review, comparing each gedatolisib arm with fulvestrant alone.
Result
Median PFS was 9.3 months (95% CI 7.2 to 16.6) with the triplet, 7.4 months (5.5 to 9.9) with the doublet, and 2.0 months (1.8 to 2.3) with fulvestrant. The hazard ratio was 0.24 (95% CI 0.17 to 0.35; P < .001) for the triplet and 0.33 (0.24 to 0.48; P < .001) for the doublet.
Other results
Overall survival was immature at the PFS analysis, with 25% deaths in the overall population. Objective response rate and duration of response were additional outcomes, but the sources give no results for them.
Safety in the trial
Grade 3 or higher treatment-related events (triplet, doublet): neutropenia 62.3%, 0.8%; stomatitis 19.2%, 12.3%; rash 4.6%, 5.4%; hyperglycemia 2.3%, 2.3%; diarrhea 1.5%, 0.8%. Treatment-related discontinuation was 2.3% with the triplet and 3.1% with the doublet.
How does Revtorpyk (gedatolisib) compare with the alternatives (Fulvestrant monotherapy, Aromatase inhibitor with an mTOR inhibitor (everolimus), Oral PI3K or AKT inhibitors with fulvestrant (alpelisib, capivasertib)) for its approved use (in combination with fulvestran, to treat hormone receptor-positive, human epidermal growth factor receptor 2-negative, locally advanced or metastatic breast cancer without a PIK3CA mutation detected fo…? Summarize head-to-head and indirect evidence, efficacy, safety and where each fits, with citations.
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Safety signals
There is no boxed warning. The label warns of severe stomatitis, severe rash, severe hyperglycemia and embryo-fetal toxicity. Stomatitis occurred in 72% with the triplet and 58% with the doublet, and Grade 3 events occurred in 22% and 12%. Steroid-containing alcohol-free mouthwash is started before treatment as prophylaxis. Rash occurred in 30% with the triplet. Blood glucose and hemoglobin A1c should be checked before and during treatment, and patients should limit sun exposure. Grade 3 or higher neutropenia was frequent with the triplet (62.3%), which reflects palbociclib, and rare with the doublet (0.8%).
What it competes with
After progression on a CDK4/6 inhibitor and an aromatase inhibitor, treatment depends on tumor biomarkers. Options include endocrine monotherapy, targeted combinations, and chemotherapy.
Fulvestrant monotherapyEndocrine backbone and the comparator in VIKTORIA-1. It is used alone or with other agents.
Aromatase inhibitor with an mTOR inhibitor (everolimus)An endocrine and targeted combination used after prior endocrine therapy, regardless of PIK3CA status. It carries stomatitis and metabolic toxicity.
Oral PI3K or AKT inhibitors with fulvestrant (alpelisib, capivasertib)Used in biomarker-selected tumors, mainly those with pathway alterations. They do not address the wild-type population studied here.
Oral selective estrogen receptor degraders (elacestrant)An option for tumors with ESR1 mutations after endocrine therapy.
Single-agent chemotherapyUsed when endocrine-based options are exhausted or visceral disease is rapidly progressing.
Bottom line for clinicians
Gedatolisib suits adults with HR-positive, HER2-negative advanced breast cancer without a detected PIK3CA mutation who progressed on a CDK4/6 inhibitor and an aromatase inhibitor. The comparator was fulvestrant alone, and overall survival data were immature. Weigh the doublet against the triplet, since the triplet had longer progression-free survival but more neutropenia. Plan for mouth care, skin monitoring and glucose monitoring, and note that patients with diabetes needing insulin or HbA1c above 6.4% were excluded.
Dosing, contraindications and full warnings are in the prescribing information.
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Last updated October 28, 2026 by 2 Minute Medicine.
For healthcare professionals. A summary of public FDA documents and published trials, not medical advice. Check the full prescribing information before prescribing.
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