HR+/HER2– Breast Cancer | Image credit:
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Treatment with gedatolisib, a pan‑PI3K/mTOR inhibitor, in combination with palbociclib (Ibrance) and fulvestrant (Faslodex) or in combination with fulvestrant alone led to clinically meaningful improvements in progression‑free survival (PFS) compared with fulvestrant alone in patients with hormone receptor–positive/HER2‑negative advanced breast cancer who had PIK3CA wild‑type disease, according to topline data from the PIK3CA wild-type cohort of the phase 3 VIKTORIA‑1 trial (NCT05501886).1
Specifically, the gedatolisib triplet reduced the risk of disease progression or death by 76% compared with fulvestrant alone (HR, 0.24; 95% CI, 0.17-0.35; P < .0001). The median PFS was 9.3 months with the triplet vs 2.0 months with fulvestrant per blinded independent central review (BICR).
Gedatolisib plus fulvestrant reduced the risk of disease progression or death by 67% compared with fulvestrant alone (HR, 0.33; 95% CI, 0.24-0.48; P < .0001). The median PFS was 7.4 months vs 2.0 months, respectively.
Full results from the PIK3CA wild‑type cohort will be presented at an upcoming medical congress in 2025. Celcuity plans to submit a new drug application for gedatolisib to the FDA in the fourth quarter of 2025.
“Patients with hormone receptor-positive, HER2-negative, PIK3CA wild-type advanced breast cancer whose disease has progressed while on, or after, treatment with a CDK4/6 inhibitor typically derive limited benefit from subsequent endocrine-based therapy. The topline data for both gedatolisib regimens from VIKTORIA-1 are potentially practice-changing,” Sara Hurvitz, MD, senior vice president of the Clinical Research Division at Fred Hutchinson Cancer Center; professor and head of the Division of Hematology and Oncology at the University of Washington, Department of Medicine; and co-principal investigator for the trial, stated in a news release.
VIKTORIA‑1 Trial Breakdown
VIKTORIA‑1 is a phase 3, open‑label, randomized study evaluating the efficacy and safety of gedatolisib plus fulvestrant with or without palbociclib in patients with locally advanced or metastatic hormone receptor–positive/HER2‑negative breast cancer who experienced disease progression on or after a CDK4/6 inhibitor and non‑steroidal aromatase inhibitor therapy.2
Patients needed to have histologically or cytologically confirmed metastatic or locally advanced disease, and they needed to be amendable to treatment with an LHRH agonist. Documented radiological disease progression on or after the last line of therapy was required, and patients needed to have radiologically evaluable disease that was measurable or non-measurable. An ECOG performance status of 0 or 1, a life expectancy of at least 3 months, and adequate bone marrow, hepatic, renal, and coagulation function were required.
Patients were stratified by confirmed PIK3CA mutation status prior to randomization. Within the PIK3CA wild‑type and PIK3CA‑mutated subgroups, patients were randomly assigned to receive gedatolisib at 180 mg on days 1, 8, and 15 of each 28-day cycle plus palbociclib at 125 mg per day for 3 weeks on and 1 week of in each cycle, and 500 mg of fulvestrant on days 1 and 15 of cycle 1, then on day 1 of subsequent cycles; gedatolisib plus fulvestrant on the same dosing schedules; or fulvestrant alone on the same schedule.
The primary end point of the trial is PFS, assessed in both PIK3CA wild‑type and PIK3CA‑mutated cohorts. Secondary end points include overall survival (OS), objective response rate, duration of response, clinical benefit rate, safety and tolerability, and patient‑reported outcomes.
Safety Analysis
Treatment discontinuations due to treatment‑related adverse effects (TRAEs) were lower for both the triplet and doublet regimens compared with Arm D of the phase 1b trial (NCT02684032) in advanced breast cancer and lower than reported in any phase 3 trials of currently approved combinations in this disease setting.1 The incidence of hyperglycemia and stomatitis was also lower than that observed in the previously reported phase 1b trial.
“To my knowledge, we have not seen phase 3 results in patients with hormone receptor–positive, HER2-negative advanced breast cancer before where there was a quadrupling of the likelihood of survival without disease progression relative to the study control,” Hurvitz added.
Reference
- Celcuity announces clinically meaningful improvement in both progression-free survival (“PFS”) primary endpoints from PIK3CA wild-type cohort of phase 3 VIKTORIA-1 trial. News Release. Celcuity. July 28, 2025. Accessed July 29, 2025. https://ir.celcuity.com/press-releases/
- Gedatolisib plus fulvestrant with or without palbociclib vs standard-of-care for the treatment of patients with advanced or metastatic HR+/HER2- breast cancer (VIKTORIA-1). ClinicalTrials.gov. Updated June 24, 2025. Accessed July 29, 2025. https://clinicaltrials.gov/study/NCT05501886