On August 26, 2026, Celcuity Inc. (Nasdaq: CELC) announced the submission of a supplemental New Drug Application (sNDA) to the U.S. Food and Drug Administration (FDA) for REVTORPYK™ (gedatolisib) in patients with hormone receptor–positive (HR+), HER2-negative (HER2−) locally advanced or metastatic breast cancer (ABC) harboring a PIK3CA mutation, following progression on or after at least one line of endocrine therapy. If approved, REVTORPYK would become the first and only therapy for PIK3CA-mutant advanced breast cancer to inhibit all class I PI3K isoforms (α, β, δ, γ) and both mTOR complexes (mTORC1 and mTORC2).

Clinical Takeaway

✔ Celcuity has filed an sNDA seeking FDA approval of REVTORPYK (gedatolisib) for PIK3CA-mutant HR+/HER2− advanced breast cancer, supported by statistically significant and clinically meaningful Phase 3 data from the VIKTORIA-1 trial.

✔ Both the REVTORPYK-triplet (plus fulvestrant and palbociclib) and REVTORPYK-doublet (plus fulvestrant) reduced the risk of disease progression or death by approximately 50% compared with alpelisib plus fulvestrant in the PIK3CA-mutant cohort.

✔ If approved, this sNDA would expand REVTORPYK’s indication to patients with PIK3CA-mutant HR+/HER2− advanced breast cancer, potentially making REVTORPYK available to patients regardless of PIK3CA mutation status and building on the existing approval for PIK3CA wild-type disease granted on July 14, 2026.

Drug Profile & Mechanism

  • Generic name: gedatolisib
  • Brand name: REVTORPYK™
  • Developer: Celcuity Inc.
  • Drug class: Pan-class I PI3K and dual mTORC1/mTORC2 inhibitor
  • Mechanism of action: REVTORPYK inhibits all four class I PI3K isoforms (α, β, δ, γ) as well as both mTOR complexes (mTORC1 and mTORC2), resulting in downstream inhibition of multiple effectors, including AKT.
  • Prior FDA approval (July 14, 2026): REVTORPYK in combination with fulvestrant, with or without palbociclib, was approved for HR+/HER2− ABC without a PIK3CA mutation following progression on or after at least one line of endocrine therapy in the metastatic setting.

Target Population

  • Tumor type: Locally advanced or metastatic breast cancer
  • Biomarker requirement: PIK3CA mutation detected
  • Receptor status: HR+ / HER2−
  • Prior therapy: Progression on or after at least one line of endocrine therapy
  • Clinical significance: Approximately 40% of patients with HR+/HER2− breast cancer have PIK3CA mutations, representing a substantial proportion of this breast cancer subtype.

Study Design

  • Trial name: VIKTORIA-1 (Phase 3)
  • Design: Open-label, randomized Phase 3 trial evaluating gedatolisib plus fulvestrant, with or without palbociclib, in adults with HR+/HER2− advanced breast cancer whose disease progressed on or after prior CDK4/6 inhibitor therapy in combination with an aromatase inhibitor.
  • PIK3CA-mutant cohort: 350 patients with confirmed PIK3CA mutations, randomized 3:3:1.
  • Comparator arm: Alpelisib + fulvestrant
  • Experimental arms:
    • REVTORPYK-triplet: REVTORPYK + fulvestrant + palbociclib
    • REVTORPYK-doublet: REVTORPYK + fulvestrant
  • Regulatory basis: The sNDA submission is supported by positive results from the PIK3CA-mutant cohort, complementing the PIK3CA wild-type cohort data that supported the July 2026 approval.

Efficacy Outcomes

  • REVTORPYK-Triplet (REVTORPYK + fulvestrant + palbociclib) vs. alpelisib + fulvestrant:
    • Risk reduction in disease progression or death: 50% (HR = 0.50; 95% CI: 0.37–0.68; p < 0.0001)
    • Median PFS: 11.1 months (REVTORPYK-triplet) vs. 5.6 months (alpelisib + fulvestrant)
    • Objective response rate (ORR): 49%
    • Median duration of response (DOR): 15.7 months
  • REVTORPYK-Doublet (REVTORPYK + fulvestrant) vs. alpelisib + fulvestrant:
    • Risk reduction in disease progression or death: 49% (HR = 0.51; 95% CI: 0.33–0.79; descriptive p = 0.0013)
    • Median PFS: 11.3 months (REVTORPYK-doublet) vs. 5.6 months (alpelisib + fulvestrant)
    • Objective response rate (ORR): 36%
    • Median duration of response (DOR): 24.2 months

Safety

  • The safety profiles of both the REVTORPYK-triplet and REVTORPYK-doublet in the PIK3CA-mutant cohort were generally consistent with previously reported data from the PIK3CA wild-type cohort of the Phase 3 VIKTORIA-1 trial.

Key Clinical Implications

✔ Potential availability regardless of PIK3CA status: If the sNDA is approved, REVTORPYK could become available to patients with HR+/HER2− locally advanced or metastatic breast cancer regardless of PIK3CA mutation status, expanding on its current indication for disease without a PIK3CA mutation detected.

✔ Head-to-head efficacy versus alpelisib: The VIKTORIA-1 PIK3CA-mutant cohort included a direct comparison with alpelisib plus fulvestrant. Both REVTORPYK regimens demonstrated approximately a 50% reduction in the risk of progression or death, with median PFS of 11.1–11.3 months versus 5.6 months with alpelisib plus fulvestrant.

✔ Durable responses with the doublet: The REVTORPYK-doublet achieved a 36% ORR and median DOR of 24.2 months, demonstrating durable responses without palbociclib in the doublet regimen.

✔ Broader PI3K/mTOR pathway blockade as a differentiator: REVTORPYK inhibits all four class I PI3K isoforms (α, β, δ, γ) and both mTOR complexes (mTORC1 and mTORC2). If approved, it would be the first and only therapy for PIK3CA-mutant advanced breast cancer with this mechanism of action.

✔ Potential expansion of the current indication: REVTORPYK already has FDA approval for HR+/HER2− advanced breast cancer without a PIK3CA mutation detected, granted July 14, 2026. Approval of the new sNDA would expand availability to the PIK3CA-mutant population.

Bottom Line

Celcuity’s sNDA submission for REVTORPYK (gedatolisib) in PIK3CA-mutant HR+/HER2− advanced breast cancer is supported by Phase 3 VIKTORIA-1 results demonstrating approximately 50% reductions in the risk of disease progression or death versus alpelisib plus fulvestrant with both REVTORPYK regimens. Median PFS was 11.1 months with the triplet and 11.3 months with the doublet versus 5.6 months with alpelisib plus fulvestrant, with a 24.2-month median DOR observed with the doublet. If approved, REVTORPYK would become the first and only therapy for PIK3CA-mutant advanced breast cancer to inhibit all class I PI3K isoforms and both mTORC1 and mTORC2 and would expand its availability across PIK3CA mutation subgroups.

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