Gedatolisib for Advanced or metastatic HR+/HER2- breast cancer
Celcuity Inc· VIKTORIA-1
Reviewed by Blane Jackson, DDS, MBA. Educational analysis only. Read the editorial policy and disclosures.
NCT05501886 on ClinicalTrials.gov →Study type
interventional
Design
Phase 3, open-label, randomize…
Target enrollment
701
Est. completion
2026-06-30
Investor scorecard
Probability of success
moderate
Timeline to catalyst
The trial is expected to complete in June 2026, but interim analyses may be conducted earlier. Investors could see data readouts in 2025 or 2026. The primary completion date is estimated, but actual data may be released sooner if the trial meets its endpoints early.
Potential stock impact
transformativeThe phase 1b data were encouraging, but phase 3 trials in breast cancer have a high failure rate. The trial is testing multiple combinations and subgroups, which increases complexity. The comparator includes alpelisib, which is already approved for PIK3CA-mutant patients, so gedatolisib must show superiority or at least non-inferiority with better tolerability. The open-label design may introduce bias, but the primary endpoint is PFS, which is objective. Overall, the probability of success is moderate, around 50-60%.
What is being tested?
This trial tests a new drug called gedatolisib, which is a type of targeted therapy known as a PI3K/mTOR inhibitor. It works by blocking certain proteins that help cancer cells grow. The drug is being tested in combination with fulvestrant (a hormone therapy) and with or without palbociclib (a CDK4/6 inhibitor) for patients with advanced or metastatic HR+/HER2- breast cancer who have already been treated with a CDK4/6 inhibitor and an aromatase inhibitor. The trial aims to see if adding gedatolisib to standard treatments can help patients live longer without their cancer progressing.
How does the trial work?
Patients are randomly assigned to one of several treatment groups. One group receives gedatolisib plus fulvestrant and palbociclib. Another group receives gedatolisib plus fulvestrant alone. The control group receives standard-of-care, which could be fulvestrant alone, fulvestrant plus palbociclib, or alpelisib plus fulvestrant, depending on the patient's PIK3CA mutation status. The trial is open-label, meaning both patients and doctors know which treatment is given. Patients continue treatment until their cancer progresses or they experience unacceptable side effects. The trial tracks how long patients live without their cancer growing (progression-free survival) and overall survival, among other measures.
What does success look like?
Success would be shown if gedatolisib combinations significantly improve progression-free survival compared to standard-of-care, in either the PIK3CA wild-type or mutant groups. For example, if the median PFS is extended by several months, that would be considered clinically meaningful. The trial also looks at overall survival, but that may take longer to show. In breast cancer trials, a hazard ratio of 0.7 or lower is often considered impressive. The trial will also assess response rates and duration of response to see if tumors shrink and for how long.
What it means for investors
For investors, positive results could be transformative for Celcuity, the sponsor, as gedatolisib is their lead asset. If the trial meets its primary endpoints, it could lead to regulatory approval and a significant market opportunity. However, the trial is complex with multiple arms and biomarker subgroups, which could complicate the analysis. Negative or mixed results could be detrimental. Investors should watch for interim analyses or data readouts, which could cause significant stock movement. The trial is expected to complete in 2026, so catalysts are a few years away. The success of this trial could position Celcuity as a major player in the HR+/HER2- breast cancer space, competing with existing CDK4/6 inhibitors and PI3K inhibitors.
Trial endpoints
Primary endpoints
Secondary endpoints
Comparator
Standard-of-care therapies (including fulvestrant alone, fulvestrant plus palbociclib, or alpelisib plus fulvestrant)
Competitive landscape
The market for HR+/HER2- breast cancer is large, with over 200,000 new cases annually in the US alone. Many patients eventually develop resistance to CDK4/6 inhibitors, creating a need for new therapies. The addressable market for gedatolisib includes patients who have progressed on prior CDK4/6 inhibitor therapy, which is a significant population. If gedatolisib can show benefit regardless of PIK3CA mutation status, it could capture a broader market than alpelisib, which is limited to mutant patients. The global market for breast cancer therapies is expected to exceed $40 billion by 2026, so even a subset of that represents a substantial opportunity.
| Drug | Sponsor | Phase | Differentiation |
|---|---|---|---|
| Alpelisib (Piqray) | Novartis | Phase 1 | Alpelisib is a PI3K inhibitor approved for PIK3CA-mutant HR+/HER2- breast cancer, but it is only used in patients with mutations and has significant side effects like hyperglycemia. |
| Inavolisib | Genentech/Roche | Phase 1 | Inavolisib is another PI3K inhibitor being tested in combination with palbociclib and fulvestrant for PIK3CA-mutant breast cancer, potentially offering better tolerability. |
| Capivasertib | AstraZeneca | Phase 1 | Capivasertib is an AKT inhibitor approved for PIK3CA/AKT/PTEN-altered breast cancer, but it is not a direct PI3K inhibitor. |
Historical context
Prior trial results
Gedatolisib has been studied in earlier phase trials. In a phase 1b trial, gedatolisib combined with palbociclib and fulvestrant showed promising activity in heavily pretreated HR+/HER2- breast cancer patients, with an overall response rate of around 30% and manageable side effects. These results led to the design of the VIKTORIA-1 trial.
Regulatory history
Gedatolisib has not received any breakthrough or fast track designations yet. The FDA has not issued any CRLs for this drug. The trial is currently in phase 3, and if successful, Celcuity would likely seek approval.
Similar drug precedents
Alpelisib was approved in 2019 for PIK3CA-mutant breast cancer, but its use is limited by side effects and the need for mutation testing. CDK4/6 inhibitors like palbociclib have become standard of care, but resistance is common. There is a precedent for PI3K inhibitors showing benefit, but also for challenges with toxicity. Gedatolisib is a dual PI3K/mTOR inhibitor, which may be more effective but also potentially more toxic.