Celcuity Inc. announced on July 30, 2026, that REVTORPYK™ (gedatolisib) has been incorporated into the National Comprehensive Cancer Network® (NCCN®) Clinical Practice Guidelines in Oncology as a preferred Category 1 regimen for second-line and subsequent-line therapy for patients with HR+/HER2- locally advanced or metastatic breast cancer without a PIK3CA mutation — following the drug’s FDA approval just weeks earlier on July 14, 2026.

Clinical Takeaway

REVTORPYK (gedatolisib) in combination with fulvestrant, with or without palbociclib, is now a preferred Category 1 second-line or subsequent-line option in the NCCN Breast Cancer Guidelines for patients with HR+/HER2- locally advanced or metastatic breast cancer lacking a PIK3CA mutation who have progressed on or after at least one line of endocrine therapy. This rapid guideline inclusion — within weeks of FDA approval — signals strong clinical consensus around the drug’s role in this molecularly defined patient population.

Drug Profile & Mechanism

  • Drug name: REVTORPYK™ (gedatolisib)
  • Developer: Celcuity Inc. (Nasdaq: CELC)
  • Mechanism of action: REVTORPYK is the only FDA-approved inhibitor of all class I PI3K isoforms (α, β, δ, γ) and both mTOR complexes (mTORC1 and mTORC2), providing comprehensive blockade of the PI3K/mTOR signaling pathway
  • FDA approval date: July 14, 2026
  • NCCN Guideline designation: Preferred Category 1 regimen

Target Population

  • Tumor type: Hormone receptor positive (HR+), HER2 negative (HER2-), locally advanced or metastatic breast cancer
  • Molecular requirement: No PIK3CA mutation detected (PIK3CA wild-type)
  • Prior therapy requirement: Progression on or after at least one line of endocrine therapy in the metastatic setting (including prior CDK4/6 inhibitor and aromatase inhibitor therapy)
  • Regimen options per NCCN: REVTORPYK + fulvestrant (doublet) or REVTORPYK + fulvestrant + palbociclib (triplet)

Study Design

The FDA approval and NCCN recommendation are based on data from the PIK3CA wild-type cohort of the Phase 3 VIKTORIA-1 trial, a global, open-label, randomized clinical study.

  • Trial name: VIKTORIA-1 (Phase 3)
  • Design: Open-label, global, randomized controlled trial
  • Comparator: Fulvestrant monotherapy
  • Experimental arms:
    • Triplet arm: REVTORPYK + palbociclib + fulvestrant
    • Doublet arm: REVTORPYK + fulvestrant
  • Patient population: HR+/HER2- locally advanced or metastatic breast cancer; progression on or after CDK4/6 inhibitor therapy and an aromatase inhibitor
  • Cohort analyzed for this approval: PIK3CA wild-type (no PIK3CA mutation)

Endpoints

  • Primary endpoint: Progression-free survival (PFS)
  • Additional endpoints: Objective response rate (ORR) and duration of response (DOR)

Efficacy Outcomes

  • REVTORPYK Triplet (REVTORPYK + palbociclib + fulvestrant) vs. Fulvestrant:
    • Median PFS: 9.3 months vs. 2.0 months (incremental improvement: +7.3 months; HR=0.24; 95% CI: 0.17–0.35; p<0.0001)
    • ORR: 32% vs. 1%
    • Median DOR: 17.5 months
  • REVTORPYK Doublet (REVTORPYK + fulvestrant) vs. Fulvestrant:
    • Median PFS: 7.4 months vs. 2.0 months (incremental improvement: +5.4 months; HR=0.33; 95% CI: 0.24–0.48; p<0.0001)
    • ORR: 28%
    • Median DOR: 12.0 months
  • Fulvestrant monotherapy: ORR of 1%; median DOR not determinable due to only one objective response observed

NCCN Guideline Designation

The NCCN Guidelines serve as a foundational clinical resource for oncologists, nurses, pharmacists, payers, and patients worldwide, guiding decisions in cancer screening, diagnosis, and treatment. NCCN is a not-for-profit alliance of 33 leading cancer centers dedicated to advancing effective, equitable, and high-quality cancer care.

  • Guideline classification: Preferred Category 1 regimen — the highest level of NCCN evidence and consensus recommendation
  • Line of therapy: Second-line or subsequent-line following progression on or after at least one line of endocrine therapy
  • Applicable tumors: HR+/HER2- locally advanced or metastatic breast cancer without a PIK3CA mutation
  • Regimens listed: REVTORPYK + fulvestrant (doublet) and REVTORPYK + fulvestrant + palbociclib (triplet)

Key Clinical Implications

✔ REVTORPYK addresses an unmet need in PIK3CA wild-type HR+/HER2- metastatic breast cancer, a population that has historically lacked targeted options given that PIK3CA-directed therapies (e.g., alpelisib) are restricted to patients with PIK3CA-mutated tumors.

✔ Molecular testing for PIK3CA mutation status is essential before treatment selection: REVTORPYK is indicated specifically for patients without a PIK3CA mutation detected, making tumor genotyping a prerequisite for appropriate patient identification.

✔ The dual-regimen flexibility — doublet or triplet — offers clinicians options to tailor treatment intensity based on patient performance status, tolerability, and prior CDK4/6 inhibitor exposure.

✔ The VIKTORIA-1 triplet arm demonstrated a hazard ratio of 0.24 — representing a 76% reduction in the risk of progression or death versus fulvestrant monotherapy — among patients who had already progressed on CDK4/6 and endocrine therapy, a historically difficult-to-treat setting.

✔ Rapid NCCN Category 1 inclusion within weeks of FDA approval underscores strong guideline committee consensus and is likely to accelerate clinician awareness and formulary consideration across oncology practices and payer systems.

✔ REVTORPYK is the first and only agent to simultaneously inhibit all four class I PI3K isoforms and both mTOR complexes, potentially overcoming the compensatory feedback loops and pathway reactivation associated with more selective PI3K or mTORC1-only inhibitors.

Bottom Line

REVTORPYK (gedatolisib), the first pan-class I PI3K/mTORC1/mTORC2 inhibitor to receive FDA approval, has been rapidly incorporated into the NCCN Breast Cancer Guidelines as a preferred Category 1 regimen for PIK3CA wild-type HR+/HER2- locally advanced or metastatic breast cancer following progression on or after at least one line of endocrine therapy. With robust Phase 3 data showing median PFS improvements of 5.4 to 7.3 months and ORRs of 28–32% versus 1% with fulvestrant alone, REVTORPYK represents a clinically meaningful advance in a setting with limited targeted options. Oncologists treating this population should ensure PIK3CA mutation testing is performed to identify eligible patients and should evaluate REVTORPYK as a preferred treatment strategy per current guidelines.

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