FDA approves REVTORPYK (gedatolisib) for PIK3CA wild-type HR-positive HER2-negative advanced breast cancer after Phase 3 VIKTORIA-1 improved progression-free survival.
Written By: Kirti Kumbhar, M. Pharm (QA)
Reviewed By: Pharmacally Editorial Team
The U.S. Food and Drug Administration has approved REVTORPYK™ (gedatolisib) in combination with fulvestrant, with or without palbociclib, for adults with hormone receptor (HR)-positive, HER2-negative, PIK3CA wild-type locally advanced or metastatic breast cancer whose disease has progressed following at least one line of endocrine therapy in the metastatic setting. The approval introduces the first and only therapy that simultaneously inhibits all class I PI3K isoforms and both mTOR complexes, expanding treatment options for the majority of patients with HR-positive breast cancer who do not harbor a PIK3CA mutation.
REVTORPYK Targets the PI3K/mTOR Pathway
REVTORPYK is the first FDA-approved pan-class I PI3K inhibitor that blocks all four PI3K isoforms (α, β, δ, and γ) while also inhibiting mTORC1 and mTORC2. By suppressing multiple components of the PI3K/AKT/mTOR signaling pathway, the drug reduces downstream AKT activation, a key driver of endocrine resistance and tumor growth in HR-positive breast cancer.
HR-positive/HER2-negative disease accounts for approximately 70% of breast cancer cases, and about 60% of these tumors are PIK3CA wild type, leaving many patients without access to mutation-specific PI3K-targeted therapies after endocrine treatment failure.
Phase 3 VIKTORIA-1 Demonstrated Significant Progression-Free Survival Benefit
The FDA approval was supported by results from the Phase 3 VIKTORIA-1 (NCT05501886) global, randomized, open-label trial evaluating gedatolisib plus fulvestrant, with or without palbociclib, in patients with locally advanced or metastatic HR-positive/HER2-negative breast cancer whose disease progressed after treatment with a CDK4/6 inhibitor and an aromatase inhibitor.
The REVTORPYK triplet regimen (gedatolisib, palbociclib, and fulvestrant) reduced the risk of disease progression or death by 76% compared with fulvestrant alone (HR 0.24; 95% CI 0.17-0.35; p<0.0001). Median progression-free survival increased from 2.0 months to 9.3 months, while the objective response rate reached 32%, compared with 1% in the control group. Median duration of response was 17.5 months.
The REVTORPYK doublet (gedatolisib plus fulvestrant) reduced the risk of progression or death by 67% (HR 0.33; 95% CI 0.24-0.48; p<0.0001). Median PFS improved to 7.4 months, representing a 5.4-month gain over fulvestrant alone. The ORR was 28%, and the median duration of response reached 12.0 months.
Experts Highlight a New Treatment Option
Brian Sullivan, Chief Executive Officer and co-founder of Celcuity, said the approval marks the first successful FDA approval of a therapy that comprehensively inhibits the PI3K/AKT/mTOR pathway after nearly two decades of research.
Sara Hurvitz, MD, co-principal investigator of the VIKTORIA-1 trial and Senior Vice President of the Clinical Research Division at Fred Hutchinson Cancer Center, noted that the approval provides oncologists with an important new option for patients with HR-positive/HER2-negative metastatic breast cancer who experience disease progression after endocrine therapy.
Commercial Launch and Development Plans
Celcuity expects to launch REVTORPYK commercially in late third quarter of 2026 and plans to provide eligible patients access through an expanded access program before full commercial availability.
The company also plans to submit a supplemental New Drug Application (sNDA) during the third quarter of 2026 seeking approval of REVTORPYK for PIK3CA-mutated HR-positive/HER2-negative advanced breast cancer, based on positive findings from the mutant cohort of the Phase 3 VIKTORIA-1 trial presented at the 2026 ASCO Annual Meeting.
Beyond breast cancer, REVTORPYK is under evaluation in the ongoing Phase 3 VIKTORIA-2 program (NCT06757634) as first-line therapy for advanced HR-positive/HER2-negative breast cancer and is also being investigated for metastatic castration-resistant prostate cancer, supporting broader development of the pan-PI3K/mTOR inhibitor across multiple solid tumors.
What This Means for Patients
The approval of REVTORPYK provides a new treatment option for people with HR-positive, HER2-negative advanced or metastatic breast cancer without a PIK3CA mutation whose disease has progressed after endocrine therapy. Clinical studies showed the treatment can delay cancer progression and increase tumor response when used with fulvestrant, with or without palbociclib. Patients should speak with their oncology team to determine whether this therapy is appropriate for their individual treatment plan.
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About the Writer
Kirti Kumbhar (LinkedIn) is an M.Pharm graduate with experience in Quality Assurance at Lupin Limited and a strong interest in clinical research, regulatory affairs, and Trial Master File (TMF) management. She has developed knowledge of regulatory documentation, quality systems, compliance, and healthcare research through her professional experience. Passionate about clinical development and continuous learning, Kirti is committed to supporting high-quality healthcare documentation, regulatory excellence, and research-driven healthcare advancements.