8-K: Celcuity's Gedatolisib Shows Strong Phase 3 Breast Cancer Results

Celcuity Inc. announced detailed positive results from the PIK3CA wild-type cohort of its Phase 3 VIKTORIA-1 clinical trial for gedatolisib in advanced breast cancer, initiating a rolling NDA submission.

Summary

• Detailed results from the PIK3CA wild-type cohort of the Phase 3 VIKTORIA-1 clinical trial were presented at the ESMO Congress 2025.
• The gedatolisib triplet (gedatolisib + palbociclib + fulvestrant) demonstrated a median progression-free survival (PFS) of 9.3 months, compared to 2.0 months for fulvestrant, an incremental improvement of 7.3 months (HR=0.24; 95% CI: 0.17-0.35; p<0.0001).
• The objective response rate (ORR) for the gedatolisib triplet was 31.5% (vs. 1% for fulvestrant) with a median duration of response (DOR) of 17.5 months.
• The gedatolisib doublet (gedatolisib + fulvestrant) showed a median PFS of 7.4 months, compared to 2.0 months for fulvestrant, an incremental improvement of 5.4 months (HR=0.33; 95% CI: 0.24-0.48; p<0.0001).
• The ORR for the gedatolisib doublet was 28.3% with a median DOR of 12.0 months.
• A rolling New Drug Application (NDA) submission has been initiated with the U.S. Food and Drug Administration's (FDA) Real-Time Oncology Review program, with completion targeted for the fourth quarter of 2025.
• The PIK3CA mutant cohort of the VIKTORIA-1 trial is 100% enrolled, and topline data for this cohort is expected in late Q1 2026 or during Q2 2026.
• Additional data from a Phase 1b clinical trial showed that for patients with PIK3CA mutant-type tumors who received the intermittent dose of gedatolisib, median PFS was 19.7 months and ORR was 64% (n=11).
• For patients with PIK3CA wild-type tumors who received the intermittent dose of gedatolisib in the Phase 1b trial, median PFS was 9.1 months and ORR was 53% (n=15).

Sentiment

Score: 9

Explanation: The clinical trial results for gedatolisib in PIK3CA wild-type advanced breast cancer are exceptionally strong, demonstrating significant and unprecedented improvements in PFS, ORR, and DOR compared to current standards. The initiation of a rolling NDA submission and promising early data for the PIK3CA mutant cohort further enhance the positive outlook.

Positives

• Gedatolisib triplet and doublet demonstrated statistically significant and clinically meaningful improvements in median PFS in PIK3CA wild-type HR+/HER2advanced breast cancer.
• Hazard ratios for the gedatolisib triplet (0.24) and doublet (0.33) are more favorable than any previously reported Phase 3 trial for HR+/HER2ABC.
• Incremental improvements in median PFS (7.3 months for triplet, 5.4 months for doublet) are higher than any previously reported Phase 3 trial for patients with HR+/HER2ABC receiving at least their second line of an endocrine therapy-based regimen.
• Gedatolisib is the first inhibitor targeting the PI3K/AKT/mTOR (PAM) pathway to demonstrate positive Phase 3 results in patients with HR+/HER2-/PIK3CA wild-type ABC whose disease progressed on or after treatment with a CDK4/6 inhibitor.
• The median DOR and incremental ORR improvement relative to control for the gedatolisib triplet and doublet are the highest reported for an endocrine therapy-based regimen in 2L HR+/HER2ABC.
• The median PFS benefit was consistent across subgroups, with the gedatolisib triplet showing higher clinical benefit in nearly all subgroups, particularly for pre/perimenopausal, endocrine therapy resistant, or visceral metastases patients.
• For patients enrolled in the United States and Canada, median PFS was 19.3 months for the gedatolisib triplet and 14.9 months for the gedatolisib doublet.
• The gedatolisib triplet and doublet were generally well tolerated with mostly low-grade treatment-related adverse events (TRAEs) and low discontinuation rates (2.3% for triplet, 3.1% for doublet).
• Overall survival, while immature, showed promising trends for both gedatolisib regimens.
• Initiation of a rolling New Drug Application (NDA) submission with the FDA's Real-Time Oncology Review program indicates an accelerated path to market.
• The PIK3CA mutant cohort of the Phase 3 VIKTORIA-1 trial is 100% enrolled, with promising Phase 1b data showing a median PFS of 19.7 months and ORR of 64% for the intermittent dose in this subgroup.

Negatives

• The most common Grade 3 TRAEs for the gedatolisib triplet included neutropenia (52.3%), stomatitis (19.2%), rash (4.6%), and hyperglycemia (2.3%).
• The most common Grade 3 TRAEs for the gedatolisib doublet included stomatitis (12.3%), rash (5.4%), and hyperglycemia (2.3%).
• Primary Grade 4 TRAEs for the gedatolisib triplet included neutropenia (10.0%) and leukopenia (0.8%).
• Primary Grade 4 TRAEs for the gedatolisib doublet included neutropenia (0.8%) and pneumonitis (0.8%).
• Overall survival data is immature, with less than one-half of the required number of events having occurred at the time of analysis.

Risks

• Certain results are based on a preliminary analysis of key data, and such data may change following a more comprehensive review of the data related to the clinical trial.
• Unforeseen delays in the planned NDA for gedatolisib.
• Ability to obtain and maintain regulatory approvals to commercialize gedatolisib.
• Unforeseen delays in clinical trials.
• Unanticipated developments that may impact the design of clinical trials.
• All forward-looking statements are subject to other risks detailed in the Annual Report on Form 10-K for the year ended December 31, 2024, as such risks may be updated in subsequent filings with the Securities and Exchange Commission.

Future Outlook

Celcuity initiated a rolling New Drug Application (NDA) submission with the U.S. Food and Drug Administration's (FDA) Real-Time Oncology Review program, targeting completion in the fourth quarter of 2025. Topline data for the PIK3CA mutant cohort of the Phase 3 VIKTORIA-1 trial is expected in late Q1 2026 or during Q2 2026. A Phase 3 clinical trial, VIKTORIA-2, evaluating gedatolisib plus a CDK4/6 inhibitor and fulvestrant as first-line treatment for patients with HR+/HER2ABC, is currently enrolling patients. Additionally, a Phase 1/2 clinical trial, CELC-G-201, evaluating gedatolisib in combination with darolutamide in patients with metastatic castration-resistant prostate cancer, is ongoing.

Management Comments

• Sara Hurvitz, MD, co-principal investigator for the trial, stated: "VIKTORIA-1 is the first study to demonstrate a statistically significant and clinically meaningful improvement in median PFS with inhibition of the PI3K/AKT/mTOR pathway in patients with PIK3CA wild-type disease, all of whom previously received a CDK4/6 inhibitor. With these results, the gedatolisib regimens represent a new potential standard of care for patients with HR+, HER2-negative, PIK3CA wild-type advanced breast cancer whose disease progressed on or after treatment with a CDK4/6 inhibitor."
• Igor Gorbatchevsky, MD, Chief Medical Officer of Celcuity, commented: "We are very excited that treatment with gedatolisib combined with fulvestrant with or without palbociclib was well-tolerated by the VIKTORIA-1 patients and that only a few patients discontinued treatment due to an adverse event. This safety profile combined with the 7.3 and 5.4-months incremental improvement in median PFS relative to fulvestrant for the gedatolisib regimens, offer potentially paradigm shifting results for patients with HR-positive, HER2-negative, PIK3CA wild-type advanced breast cancer."
• Brian Sullivan, CEO and co-founder of Celcuity, announced: "We are pleased to announce that the PIK3CA mutant cohort of the VIKTORIA-1 study is 100% enrolled. Based on our current forecast of reaching the event threshold that will trigger primary analysis in the PIK3CA mutant cohort, we expect to report topline data sometime in late Q1 2026 or during Q2 2026."
• Igor Gorbatchevsky, MD, Chief Medical Officer of Celcuity, added: "We are very encouraged by the median PFS of 14.6 months found in the entire PIK3CA mutant patient subgroup. While the sample size is small, the median PFS from patients whose tumors had PIK3CA mutations and who received the Phase 3 intermittent gedatolisib dose is promising and consistent with the results from the overall group. We are looking forward to reporting Phase 3 data for this patient subgroup in 2026."

Industry Context

HR+/HER2breast cancer is the most common subtype, accounting for approximately 70% of all breast cancers, and resistance to CDK4/6 inhibitors and current endocrine therapies is a significant challenge. Gedatolisib, as an investigational multi-target PI3K/AKT/mTOR (PAM) inhibitor, offers a differentiated mechanism of action compared to currently approved single-target inhibitors, aiming to overcome adaptive resistance. The reported Phase 3 results position gedatolisib as a potential new standard of care for patients with HR+/HER2advanced breast cancer, particularly those with PIK3CA wild-type tumors who have progressed on prior CDK4/6 inhibitor treatment, addressing a critical unmet medical need.

Comparison to Industry Standards

• The hazard ratios for the gedatolisib triplet (0.24) and doublet (0.33) are more favorable than any previously reported by any Phase 3 trial for patients with HR+/HER2ABC.
• The 7.3and 5.4-months incremental improvements in median PFS for the gedatolisib triplet and gedatolisib doublet over fulvestrant, respectively, are higher than have ever been reported by any Phase 3 trial for patients with HR+/HER2ABC receiving at least their second line of an endocrine therapy-based regimen.
• Gedatolisib is the first inhibitor targeting the PI3K/AKT/mTOR (PAM) pathway to demonstrate positive Phase 3 results in patients with HR+/HER2-/PIK3CA wild-type ABC whose disease progressed on or after treatment with a CDK4/6 inhibitor.
• The median DOR and incremental ORR improvement relative to control for the gedatolisib triplet and doublet are the highest reported for an endocrine therapy-based regimen in 2L HR+/HER2ABC.
• Unlike single-target inhibitors of the PAM pathway, gedatolisib has demonstrated equal potency and comparable cytotoxicity in PIK3CA-mutant and wild-type breast tumor cells in nonclinical studies and early clinical data, suggesting a broader applicability.

Stakeholder Impact

• Shareholders: Highly positive impact due to strong clinical data, potential for a new standard of care, and progress towards regulatory approval, likely increasing company valuation.
• Patients: Significant positive impact by offering a new, highly effective treatment option for HR+/HER2advanced breast cancer patients who have progressed on prior therapies, particularly those with PIK3CA wild-type tumors.
• Healthcare Providers: Provides a new, potentially practice-changing therapeutic regimen for a challenging patient population with high unmet needs.
• Employees: Positive impact on morale and job security due to successful clinical development and potential commercialization.
• Regulatory Authorities: Engaged through the Real-Time Oncology Review program, indicating a streamlined review process for a promising therapy.

Next Steps

• Complete rolling New Drug Application (NDA) submission with the FDA (targeted Q4 2025).
• Report topline data for the PIK3CA mutant cohort of the Phase 3 VIKTORIA-1 trial (expected late Q1 2026 or Q2 2026).
• Continue enrollment for Phase 3 VIKTORIA-2 clinical trial (first-line treatment for HR+/HER2ABC).
• Continue Phase 1/2 clinical trial (CELC-G-201) for metastatic castration-resistant prostate cancer.
• Celcuity management will host a webcast and conference call on October 20, 2025, to discuss the additional results.

Key Dates

Recommendation

The Phase 3 VIKTORIA-1 trial results for gedatolisib in PIK3CA wild-type HR+/HER2advanced breast cancer are exceptionally positive, demonstrating unprecedented improvements in progression-free survival, objective response rate, and duration of response compared to existing treatments. The hazard ratios and incremental PFS benefits are superior to any previously reported Phase 3 trial in this setting, positioning gedatolisib as a potential new standard of care. The initiation of a rolling NDA submission with the FDA's Real-Time Oncology Review program indicates an accelerated path to market. While overall survival data is immature and some adverse events were noted, the overall efficacy and tolerability profile, combined with promising early data from the PIK3CA mutant cohort, suggest a high probability of regulatory approval and significant commercial potential. This represents a major de-risking event and a substantial value inflection point for the company.

Keywords

Celcuity, CELC, gedatolisib, VIKTORIA-1, Phase 3, breast cancer, HR-positive, HER2-negative, PIK3CA wild-type, PIK3CA mutant, advanced breast cancer, oncology, clinical trial, PFS, ORR, DOR, NDA, FDA, ESMO, PI3K/AKT/mTOR, PAM pathway, targeted therapy, CDK4/6 inhibitor, fulvestrant, palbociclib