Phase 3 VIKTORIA-1 Trial Meets Primary End Point in PIK3CA-Mutant Advanced Breast Cancer

Celcuity announced positive topline results from the phase 3 VIKTORIA-1 trial (NCT05501886) evaluating gedatolisib plus fulvestrant (Faslodex; AstraZeneca) with or without palbociclib (Ibrance; Pfizer) in patients with hormone receptor–positive (HR+), HER2-negative (HER2–), PIK3CA-mutant advanced breast cancer whose disease progressed following treatment with a CDK4/6 inhibitor and an aromatase inhibitor.^1,2

Clinically Meaningful PFS Improvement Observed

According to the company, the study achieved its primary end point, demonstrating a statistically significant and clinically meaningful improvement in progression-free survival (PFS) with the gedatolisib triplet regimen—gedatolisib, fulvestrant, and palbociclib—compared with alpelisib (Piqray; Novartis) plus fulvestrant.¹ The gedatolisib doublet regimen, consisting of gedatolisib and fulvestrant, also demonstrated statistically significant and clinically meaningful PFS improvement despite not being part of the primary hierarchical efficacy analysis.¹

Both regimens were generally well tolerated, with manageable safety profiles and no new safety signals identified. Detailed efficacy and safety findings are expected to be presented during a late-breaking oral abstract session at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting.¹

“Patients with PIK3CA-mutant HR+/HER2– advanced breast cancer whose disease has progressed while on or after treatment with a CDK4/6 inhibitor typically derive modest benefit from subsequent therapies that target only PI3Kα or AKT,” said Sara Hurvitz, MD, senior vice president, Clinical Research Division, Fred Hutch Cancer Center, and co–principal investigator for the trial.¹ “VIKTORIA-1 represents the first phase 3 study to demonstrate that comprehensively blocking the PI3K/AKT/mTOR, or PAM, pathway can significantly improve outcomes for patients with PIK3CA mutations compared to therapies only targeting a single component of this pathway.”¹

Addressing Resistance After CDK4/6 Inhibition

HR+/HER2– breast cancer accounts for approximately 70% of all breast cancer diagnoses, with nearly 40% of tumors harboring PIK3CA mutations.^1,3 Resistance following endocrine therapy and CDK4/6 inhibition remains a major challenge in metastatic disease, particularly in patients with activation of the PI3K/AKT/mTOR pathway.⁴

Gedatolisib is an investigational multitarget PAM inhibitor designed to inhibit all 4 class I PI3K isoforms as well as mTORC1 and mTORC2, potentially providing broader pathway suppression than currently approved single-target inhibitors. Investigators noted that comprehensive pathway inhibition may help overcome adaptive resistance mechanisms observed with selective PI3K or AKT inhibition.^1,2

“These positive topline results demonstrate the potential for gedatolisib to become a transformative new medicine for the treatment of patients with PIK3CA mutant HR+/HER2– advanced breast cancer,” said Igor Gorbatchevsky, MD, chief medical officer of Celcuity.¹ “When considered alongside previously presented data from the VIKTORIA-1 PIK3CA wild-type cohort, the gedatolisib regimens have now demonstrated the potential to improve the standard of care in the second-line setting regardless of the PIK3CA status of a patient’s tumor.”¹

Regulatory Momentum Continues

The FDA previously granted priority review to Celcuity’s new drug application for gedatolisib in patients with HR+/HER2– PIK3CA wild-type advanced breast cancer, assigning a Prescription Drug User Fee Act target date of July 17, 2026. Celcuity indicated that the new mutant-cohort findings will support a supplemental new drug application submission.¹

“We believe the results from the VIKTORIA-1 study validate our pioneering approach to targeting cancers involving the PI3K/AKT/mTOR pathway,” said Brian Sullivan, chairman, CEO, and cofounder of Celcuity.¹ “Researchers have sought for nearly 20 years to develop a drug that blockades this pathway comprehensively without inducing unacceptable levels of toxicity.¹

As treatment options continue to evolve for patients with HR+/HER2– advanced breast cancer, the VIKTORIA-1 findings may signal a potential shift in the management of patients with PIK3CA-mutant disease following CDK4/6 inhibitor progression. For pharmacists, the emergence of comprehensive PI3K/AKT/mTOR pathway inhibition with gedatolisib could introduce new considerations surrounding adverse effect monitoring, adherence support, and regimen optimization in the metastatic setting. Pharmacists may also play a critical role in identifying eligible patients through biomarker-driven treatment approaches and helping guide multidisciplinary care as novel targeted therapies continue to expand in breast cancer management.

REFERENCES

1. Celcuity’s phase 3 VIKTORIA-1 trial achieves primary endpoint with clinically meaningful improvement in progression-free survival in PIK3CA mutant cohort. News release. Celcuity Inc. May 1, 2026. Accessed May 8, 2026. https://ir.celcuity.com/news-releases/news-release-details/celcuitys-phase-3-viktoria-1-trial-achieves-primary-endpoint

2. Hurvitz SA, Layman RM, Curigliano G, et al. VIKTORIA-1 trial of gedatolisib plus fulvestrant with or without palbociclib in hormone receptor-positive/HER2-/PIK3CA wild-type advanced breast cancer. J Clin Oncol. 2026;44(12):1108-1119. doi:10.1200/JCO-25-02643

3. Key statistics for breast cancer. American Cancer Society. January 13, 2026. Accessed May 8, 2026. https://www.cancer.org/cancer/types/breast-cancer/about/how-common-is-breast-cancer.html

4. Gedatolisib in VIKTORIA-1: positive topline data in PIK3CA-mutant metastatic breast cancer. OncoDaily. May 3, 2026. Accessed May 8, 2026. https://oncodaily.com/oncolibrary/breast-oncology/viktoria-1-2