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FDA Approves Revtorpyk (Gedatolisib), First Pan-PI3K/mTOR Inhibitor for HR-Positive, HER2-Negative Advanced Breast Cancer

The FDA approved Celcuity's gedatolisib for PIK3CA wild-type HR+/HER2- advanced breast cancer after it more than tripled progression-free survival over fulvestrant alone in the Phase 3 VIKTORIA-1 trial.

Biotech & Medicine Oncology
FDA approval breast cancer gedatolisib Revtorpyk Celcuity oncology PI3K inhibitor clinical trial
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Overview

The U.S. Food and Drug Administration approved gedatolisib, sold as Revtorpyk, on July 14, 2026, for adults with hormone receptor-positive, HER2-negative locally advanced or metastatic breast cancer whose tumors lack a PIK3CA mutation, according to Oncology Nursing Society. The drug is approved for patients who have progressed on at least one line of endocrine therapy in the metastatic setting, and is given in combination with fulvestrant, with or without palbociclib, Oncology Nursing Society reported. Fulvestrant and palbociclib are marketed as Faslodex and Ibrance, respectively, according to Breastcancer.org.

Celcuity, the drug’s developer, said Revtorpyk “is the only inhibitor of class I PI3K isoforms (α, β, δ, γ) and mTOR complexes mTORC1 and mTORC2 to receive FDA approval,” according to the company’s announcement carried on GlobeNewswire. Oncology Nursing Society similarly described gedatolisib as “the first FDA-approved therapy that inhibits all class I PI3K isoforms and mTOR complexes,” according to Oncology Nursing Society.

What We Know

  • The approval is based on Study 1 of the Phase 3 VIKTORIA-1 trial (NCT05501886), which enrolled 392 adults with locally advanced or metastatic HR-positive, HER2-negative breast cancer, randomizing them to gedatolisib plus fulvestrant and palbociclib, gedatolisib plus fulvestrant alone, or fulvestrant alone, according to Oncology Nursing Society.
  • Median progression-free survival for the triplet combination reached 9.3 months, compared with 2.0 months for fulvestrant alone, a difference CancerNetwork reported was statistically significant with a hazard ratio of 0.24 and a p-value below .0001.
  • The doublet combination of gedatolisib and fulvestrant produced median progression-free survival of 7.4 months versus the same 2.0-month control, with a hazard ratio of 0.33 and a p-value below .0001, according to CancerNetwork.
  • Celcuity said those results translated into a 76% reduction in the risk of disease progression or death for the triplet regimen and a 67% reduction for the doublet, both measured against fulvestrant alone, according to the company’s GlobeNewswire announcement.
  • Objective response rates were 32% in the triplet arm and 28% in the doublet arm, compared with 1% for fulvestrant alone, and median duration of response reached 17.5 months in the triplet arm and 12.0 months in the doublet arm, according to CancerNetwork.
  • The recommended dose is 180 mg administered intravenously over 30 minutes once weekly on days 1, 8 and 15 of each 28-day cycle, according to Oncology Nursing Society and Breastcancer.org.
  • Common side effects include mouth and throat sores, low white blood cell counts, nausea, vomiting, rash, fatigue, diarrhea and hyperglycemia, according to Breastcancer.org. Celcuity’s release put specific rates on several of those events in the triplet and doublet arms respectively: stomatitis in 72% and 58% of patients, rash in 30% and 40%, and hyperglycemia in 46% and 57%, according to the GlobeNewswire announcement.
  • Patients who are pregnant or trying to become pregnant should not receive gedatolisib because of embryo-fetal toxicity risk, according to Breastcancer.org.
  • “The PI3K/AKT/mTOR, or PAM, pathway is one of the most important targets in cancer, but comprehensively inhibiting it has stymied researchers and drug developers for nearly two decades,” said Brian Sullivan, CEO and co-founder of Celcuity, according to the GlobeNewswire announcement.
  • Celcuity said it plans to submit a supplemental New Drug Application to the FDA in the third quarter of 2026 seeking approval of Revtorpyk for patients whose tumors carry a PIK3CA mutation, based on results from a separate cohort of the VIKTORIA-1 trial, according to the GlobeNewswire announcement.

What We Don’t Know

  • Celcuity has not yet disclosed pricing for Revtorpyk ahead of its anticipated launch later in the third quarter of 2026.
  • The efficacy and safety profile of gedatolisib in the PIK3CA-mutant patient population — the subject of the planned supplemental filing — has been presented separately at a medical meeting but has not yet been reviewed or acted on by the FDA, so it is not addressed here in detail.
  • Longer-term overall survival data from VIKTORIA-1 were not available in the sources reviewed for this article.

Analysis

The approval gives clinicians a new option for a patient population — PIK3CA wild-type, HR-positive, HER2-negative breast cancer that has progressed after endocrine therapy — that has had comparatively few targeted therapies aimed specifically at the PI3K/AKT/mTOR signaling pathway. Sullivan’s framing of the pathway as one that has “stymied researchers and drug developers for nearly two decades” points to why earlier attempts to drug PI3K and mTOR simultaneously largely stalled in the clinic on toxicity or efficacy grounds. Whether Revtorpyk’s tolerability profile — including the roughly 1-in-3 to 3-in-5 patients who experienced stomatitis depending on regimen — proves manageable enough for broad community-oncology adoption will likely shape how quickly it is taken up outside the trial setting.