FDA Approaching July 17 Decision on Celcuity's Gedatolisib as First Targeted Therapy for PIK3CA Wild-Type Breast Cancer

FDA Approaching July 17 Decision on Celcuity's Gedatolisib as First Targeted Therapy for PIK3CA Wild-Type Breast Cancer

The U.S. Food and Drug Administration (FDA) is expected to issue a highly anticipated regulatory decision by July 17, 2026, on Celcuity's New Drug Application (NDA) for gedatolisib—a first-in-class, pan-Class I PI3K and dual mTORC1/mTORC2 inhibitor—combined with palbociclib and fulvestrant for patients with hormone receptor-positive, HER2-negative (HR+/HER2-) advanced or metastatic breast cancer whose tumors are PIK3CA wild-type (non-mutant) and have progressed on prior CDK4/6 inhibitor therapy.

The Scientific and Clinical Context

Approximately 60% of patients with HR+/HER2- advanced breast cancer have PIK3CA wild-type disease. While patients with PIK3CA mutations can be treated with isoform-selective PI3Kα inhibitors like alpelisib (Piqray) or AKT inhibitors like capivasertib (Truqap), wild-type patients currently have no approved targeted options in the second-line post-CDK4/6 setting. They are typically relegated to fulvestrant monotherapy, which yields a historical median progression-free survival (PFS) of only two months.

Gedatolisib circumvented this limitation by simultaneously targeting all four Class I PI3K isoforms ($\alpha$, $\beta$, $\gamma$, $\delta$) as well as both mTOR complexes (mTORC1 and mTORC2). This broad-spectrum blockade prevents the pathway-reactivating feedback loops and alternative isoform signaling that render selective inhibitors ineffective in wild-type tumors.

According to a review of the upcoming decision:

"If the agency approves it, roughly 37,000 women per year in the United States who carry PIK3CA wild-type HR+/HER2- advanced breast cancer will gain a treatment option that, in the Phase 3 trial supporting the application, extended progression-free survival from two months to more than nine — a 76% risk reduction — compared with the current standard of care." — TechTimes, July 10, 2026

Phase 3 VIKTORIA-1 Trial Evidence

The NDA is supported by the Phase 3 VIKTORIA-1 trial (NCT05501886) in 392 patients with PIK3CA wild-type HR+/HER2- advanced breast cancer. The trial compared a triplet regimen (gedatolisib + palbociclib + fulvestrant) and a doublet regimen (gedatolisib + fulvestrant) against fulvestrant monotherapy:

• PFS (Triplet): The triplet achieved a median PFS of 9.3 months versus 2.0 months for fulvestrant monotherapy, representing a 76% reduction in the risk of disease progression or death (HR 0.24; 95% CI: 0.17–0.35; P < .0001).
• PFS (Doublet): The doublet achieved a median PFS of 7.4 months versus 2.0 months (HR 0.33; 95% CI: 0.24–0.48; P < .0001).
• Objective Response Rate (ORR): 31.5% for the triplet and 28.3% for the doublet, compared to just 1.0% for the fulvestrant control arm.
• Tolerability: Unlike alpelisib, which causes severe, dose-limiting hyperglycemia (occurring in nearly 58% of patients in its pivotal trial), grade 3 hyperglycemia occurred in only 2.3% of patients in both gedatolisib arms. The dominant adverse event was stomatitis (mouth sores), occurring at any grade in 60% of patients but managed effectively with prophylactic steroid mouthwash.

Next Steps and Future Outlook

The NDA is under review through the FDA's Real-Time Oncology Review (RTOR) program and was granted Priority Review. If approved, the launch will require a significant increase in biomarker testing penetration, as many community oncologists do not routinely test for PIK3CA status unless seeking to qualify a patient for mutation-specific therapies.¹

Celcuity is also advancing gedatolisib into the PIK3CA-mutant population. In May 2026, the company announced that the PIK3CA-mutant cohort of VIKTORIA-1 met its primary endpoint, showing a statistically significant PFS improvement over alpelisib plus fulvestrant, which will support a future supplemental NDA. Meanwhile, the Phase 3 VIKTORIA-2 trial is actively evaluating gedatolisib in the first-line setting.