Key Takeaways
- Historic Progression-Free Survival Benefit in HR+/HER2- Breast Cancer: Gedatolisib reduced the risk of progression or death by 76% (triplet) and 67% (doublet), marking unprecedented results in a Phase III setting for this population.
- Favorable Safety and Tolerability Profile: Both gedatolisib regimens had lower treatment discontinuation rates than observed in Phase Ib or other Phase III trials involving approved combinations.
- Regulatory Pathway and Presentation Timeline: Full VIKTORIA-1 data to be presented later in 2025; Celcuity plans to submit an NDA for gedatolisib to the FDA in Q4 2025.
Results from the PIK3CA wild-type cohort of the Phase III VIKTORIA-1 trial (NCT05501886) showed that Celcuity’s gedatolisib, when combined with fulvestrant with or without palbociclib, produced statistically significant and clinically meaningful improvements in progression-free survival (PFS) in patients with HR-positive, HER2-negative, PIK3CA wild-type advanced breast cancer (ABC) who had progressed on or after treatment with CDK4/6 and aromatase inhibitors. According to the company, full data from this cohort will be presented at an upcoming medical conference later this year.1
How did Gedatolisib Perform in the PIK3CA Wild-Type Cohort of VIKTORIA-1?
“Patients with HR-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,” said Sara Hurvitz, SVP, clinical research division, Fred Hutchinson Cancer Center, professor, head, division of hematology, oncology, department of medicine, University of Washington, trial co-principal investigator, in a press release. “The topline data for gedatolisib regimens from VIKTORIA-1 are potentially practice-changing. To my knowledge, we have not seen Phase III results in patients with HR-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.”
VIKTORIA-1 Trial Design and Patient Population
- The open-label, randomized VIKTORIA-1 trial evaluated the efficacy and safety of gedatolisib in combination with fulvestrant with or without palbociclib in 701 adults with HR+/HER2- ABC whose disease progressed on or after prior CDK4/6 therapy in combination with an aromatase inhibitor.
- Patients were randomly assigned in a 1:1:1 ratio to receive a regimen of either gedatolisib, palbociclib, and fulvestrant; gedatolisib and fulvestrant; or fulvestrant.
- From there, patients who met the eligibility criteria and have confirmed PI3KCA mutations were randomly assigned in a 3:3:1 ratio to receive a regimen of either the gedatolisib triplet, alpelisib and fulvestrant, or the gedatolisib doublet.
- The primary endpoint of the trial was PFS defined as the time from randomization to death or the first documented progression confirmed by RECIST 1.1 criteria, as determined by blinded independent central review.1,2
Efficacy Results from VIKTORIA-1 Trial
- Results showed that the triplet regimen reduced the risk of disease progression or death by 76%, achieving a median PFS of 9.3 months compared to two months with fulvestrant.
- The doublet reduced the risk of disease progression or death by 67%, with a median PFS of 7.4 months.
- Fewer patients discontinued treatment due to treatment-related adverse events with the gedatolisib triplet and doublet regimens compared to Arm D of the Phase Ib trial in ABC and rates were also lower than those seen in any Phase III trials involving currently approved drug combinations for HR+/HER2- ABC.1
Expert and Executive Commentary
“The topline data from VIKTORIA-1 demonstrate the potential for gedatolisib to become a transformative new medicine for the treatment of patients with HR-positive, HER2-negative, PIK3CA wild-type advanced breast cancer whose disease progressed on or after treatment with CDK4/6 inhibitors,” said Igor Gorbatchevsky, MD, chief medical officer, Celcuity, in the press release. “The 7.3 and 5.4-months incremental improvement in median PFS relative to fulvestrant for the gedatolisib regimens are potentially paradigm shifting results. We are also 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.”
Breast Cancer Burden in the United States
Current estimates suggest that 13% of women in the United States will be diagnosed with breast cancer during their lifespan, making it the most common cancer in women. Annually, 32% of all newly diagnosed cancers in women are breast cancer. By the end of 2025, approximately 316,950 women will be diagnosed with invasive breast cancer, while 42,170 are expected to die.3
Future Outlook
“The efficacy improvement relative to the control that each of the gedatolisib regimens demonstrated was historic for this patient population,” said Brian Sullivan, chairman, CEO, co-founder, Celcuity, in the press release. “We are excited about the potential opportunity to provide a breakthrough therapeutic option for patients with HR-positive, HER2-negative, PIK3CA wild-type advanced breast cancer.”
References
- Celcuity Announces Clinically Meaningful Improvement in Both Progression-Free Survival (“PFS”) Primary Endpoints from PIK3CA Wild-Type Cohort of Phase 3 VIKTORIA-1 Trial. GlobeNewswire. July 28, 2025. Accessed July 28, 2025. https://www.globenewswire.com/news-release/2025/07/28/3122331/0/en/Celcuity-Announces-Clinically-Meaningful-Improvement-in-Both-Progression-Free-Survival-PFS-Primary-Endpoints-from-PIK3CA-Wild-Type-Cohort-of-Phase-3-VIKTORIA-1-Trial.html
- 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) (VIKTORIA-1). Clinicaltrials.gov. Accessed July 28, 2025. https://clinicaltrials.gov/study/NCT05501886?term=VIKTORIA-1&rank=1
- Breast Cancer Facts and Statistics. Breastcancer.org. Accessed July 28, 2025. https://www.breastcancer.org/facts-statistics?gad_source=1&gad_campaignid=2038810&gbraid=0AAAAAD_jk-7hc0H5pD_vkzOWGTPpKXSbv&gclid=CjwKCAjwv5zEBhBwEiwAOg2YKNPKSUZkEnRIxAUhkyTmpToVBE_bP_XHuS17q6YvRFVduloAuz3r7BoCWfAQAvD_BwE
