At the European Society for Medical Oncology (ESMO) 2025 event, held in Berlin, Germany, between 17-21 October, Celcuity presented results of its VIKTORIA-1 trial. This trial compared gedatolisib, a phosphoinositide 3-kinase (Pi3K)/protein kinase B/mammalian target of rapamycin (PAM) pathway inhibitor, in combination with fulvestrant with or without Ibrance, Pfizer’s cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor, against fulvestrant alone in metastatic hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2) breast cancer (BC) patients. Eligible patients enrolled on the trial had been previously treated with at least two lines of endocrine therapy for advanced BC, including one line containing a CDK4/6 inhibitor. The results presented focused on the PIK3A wild-type (WT) cohort. Because current labels for pathway-targeted agents typically require specific alterations, many PIK3CA-WT patients are not eligible for therapies targeting the Pi3K pathway such as AstraZeneca’s Truqap or Roche’s Itovebi.
Patients enrolled in the trial were randomised 1:1:1 to the triplet arm (gedatolisib plus Ibrance plus fulvestrant), the doublet arm (gedatolisib plus fulvestrant) and the control arm (fulvestrant). Median progression-free survival (PFS) was 9.3 months in the triplet arm versus 2.0 months in the control arm (hazard ratio [HR], 0.24; 95% confidence interval [CI]: 0.17-0.35). Median PFS was 7.4 months in the doublet arm (HR, 0.33; 95% CI: 0.24-0.48). Overall survival data is immature for either experimental arm. However, a positive trend was reported for both experimental arms with a HR of 0.69 (95% CI: 0.43-1.12) for the triplet and 0.74 (95% CI: 0.46-1.19) for the doublet. Treatment discontinuation due to treatment-related adverse events was low with 2.3% of the patients on the triplet and 3.1% of patients on the doublet. Any-grade hyperglycaemia occurred in 9.2% (triplet) and 11.5% (doublet), which is notably low for patients receiving a Pi3K-pathway-targeting agent.
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The design of this clinical trial and the agent’s profile position Celcuity well. If approved, gedatolisib would be the first PAM-pathway–targeting therapy to demonstrate positive Phase 3 results specifically in the PIK3CA-WT population post-CDK4/6. The robust triplet results will also boost Pfizer as it will increase prescriptions of this agent in the second line, which is currently competing with Eli Lilly’s Verzenio and Novartis’ Kisqali in the first-line setting. Leading data and analytics company GlobalData is still awaiting results from the PiK3CA-positive cohort of the trial, which will determine whether gedatolisib can potentially challenge or displace Truqap or Itovebi. Companies marketing oral selective estrogen receptor degraders (SERDs), including Eli Lilly, Stemline Menarini, and AstraZeneca may also have reason for concern as this trial did not exclude patients positive for estrogen receptor 1. This inclusion could further narrow the number of eligible patients who would receive their oral SERDs. GlobalData’s analyst consensus forecast for gedatolisib is projected to generate $827m in 2031 while Truqap and Itovebi gains $1.8bn and $1.9bn, respectively, in the same year.
