FDA Takes Up Gedatolisib Filing for PIK3CA-Mutant Breast Cancer

Celcuity's gedatolisib is back at the FDA's door, this time for the PIK3CA-mutant slice of HR+/HER2- locally advanced or metastatic breast cancer. The agency accepted the supplemental new drug application and stamped a PDUFA target action date of June 25, 2027. The filing covers adults whose disease progressed on at least one line of endocrine therapy in the metastatic setting. Gedatolisib works by blocking class I PI3K isoforms along with mTORC1 and mTORC2.

The data package comes from the PIK3CA-mutant cohort of VIKTORIA-1, which randomized 350 patients 3:3:1 to the gedatolisib triplet, alpelisib (Piqray) plus fulvestrant, or the gedatolisib doublet. Median progression-free survival hit 11.1 months with gedatolisib, fulvestrant and palbociclib versus 5.6 months for alpelisib plus fulvestrant, a hazard ratio of 0.50. The doublet posted 11.3 months, with a hazard ratio of 0.51 in a descriptive comparison. Objective response rates landed at 48.9%, 35.7% and 26.0%, and median duration of response ran 15.7, 24.2 and 7.5 months respectively. Overall survival data were still immature, with no values or hazard ratios reported.

Tolerability splits the two approaches. Treatment discontinuation from related adverse events hit 2.6% on the triplet, 3.8% on the doublet and 7.1% on alpelisib plus fulvestrant. Grade 3 or higher neutropenia struck 58.8% of triplet patients and 0% of doublet patients, while hyperglycemia ran 2.6%, 0% and 14.5% across the arms and rash 6.5%, 5.8% and 15.1%. Stomatitis was the common thread: 72% on the triplet with 22% grade 3, and 58% on the doublet with 12% grade 3. One grade 5 related event occurred in the triplet arm and was tied to palbociclib; alpelisib plus fulvestrant saw two.

Sara Hurvitz, MD, of Fred Hutch Cancer Center, called the therapeutic index the headline. In an interview with Targeted Onc, she said: “It's very exciting to think about having a regimen with a therapeutic index this much better, not only because of its efficacy but because of its tolerability. This is something I would want to offer my patients, and I think it also gives them real hope.”

The FDA already cleared gedatolisib with fulvestrant, with or without palbociclib, on July 14, 2026 for PIK3CA wild-type disease. In that cohort, median PFS reached 9.3 months on the triplet against 2.0 months with fulvestrant alone, a 76% cut in progression or death risk, while the doublet hit 7.4 months and a 67% reduction. Approval of this new filing would make the drug available second-line regardless of PIK3CA status. HR+/HER2- is the most common breast cancer subtype at roughly 70% of cases, and about 40% of those tumors carry PIK3CA mutations.

More trials are running behind it. VIKTORIA-2 is split into two first-line studies: one testing gedatolisib with palbociclib and fulvestrant in endocrine-resistant disease, the other pairing gedatolisib with palbociclib and letrozole in endocrine-sensitive disease. The phase 1b/2 CELC-G-201 study is also testing gedatolisib alongside darolutamide (Nubeqa) in metastatic castration-resistant prostate cancer. Gedatolisib previously picked up breakthrough therapy and fast track designations.