A phase 3 study of gedatolisib plus fulvestrant with or without palbociclib (Ibrance) with or without standard of care treatment is actively recruiting patients with advanced or metastatic hormone receptor-positive, HER2-negative breast cancer (VIKTORIA-1; NCT05501886).1
Gedatolisib is a PI3K and mTOR inhibitor which preclinically demonstrated the ability to decrease cell viability in tumor cell lines.2 Phase 1b data from gedatolisib in patients with advanced solid tumors showed that when the agent is combined with chemotherapy, patients derive clinical benefit. Gedatolisib also demonstrated atolerabile safety profile in the phase 1b study.3
About VIKTORIA-1
Trial Name: Phase 3, Open-Label, Randomized, Study Comparing Gedatolisib Combined With Fulvestrant & With or Without Palbociclib to Standard-of-Care Therapies in Patients With HR-Positive, HER2-Negative Advanced Breast Cancer Previously Treated With a CDK4/6 Inhibitor in Combination w/Non-Steroidal Aromatase Inhibitor Therapy
ClinicalTrials.gov Identifier: NCT05501886
Sponsor: Celcuity, Inc.
Recruitment Contact: Nadene Zack, MS844-310-3900nzack@celcuity.com
Completion Date: September 30, 2026
In VIKTORIA-1, an open-label, randomized clinical, phase 3 trial, approximately 701 patients with HR-positive, HER2-negative advanced breast cancer who were previously treated with a CDK4/6 inhibitor plus a non-steroidal aromatase inhibitor. Patients enrolled will be randomized to 1 of 6 treatment arms.
Patients with PIK3CA wild-type in experimental arm A will receive gedatolisib 180 mg intravenously (IV) given weekly for 3 weeks in combination with palbociclib25 mg orally daily for 3 weeks plus fulvestrant 500 mg in 2 x 5 mL injection every 2 weeks during cycles 1 and every 4 weeks thereafter. Those randomized to experimental arm B will receive gedatolisib plus fulvestrant. In arm C, patients are treated with fulvestrant, and this arm is the comparator for arms A and B.
In arm D, patients with PIK3CA-mutated disease will receive the experimental combination of gedatolisib, palbociclib, and fulvestrant which is compared with the combination of fulvestrant and alpelisib (Piqray) 300 mg orally daily for 4 weeks (arm E). A doublet of gedatolisib plus fulvestrant will be investigated in arm F and compared with arm E.
The primary end point of the study is progression-free survival (PFS) in both the PIK3CA wild-type and mutated subgroups. The secondary end points of the study include overall survival, overall response rate, duration of response, time to response, clinical benefit rate, quality of life, patient-reported outcomes, and the type, incidence, and severity of adverse events.
To be eligible for inclusion in the study, patients must have histologically or cytologically confirmed disease, adequate archival or new tissue for biomarker testing, an ECOG performance status of 0 or 1, a life expectancy of at least 3 months, and adequate bone marrow, hepatic, renal, and coagulation function. All patients are required to have progressed on treatment with a CDK4/6 and AI inhibitor combination.
VIKTORIA-1 will be conducted at 210 locations in the North America, South America, Europe, Asia, and the Oceania. The study is schedule to reach primary completion in September of 2024.
REFERENCES:
1. Gedatolisibplus 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 December 21, 2022.
2. Murase Y, Hosoya K, Sato T, et al. Antitumor activity of the dual PI3K/mTOR inhibitor gedatolisib and the involvement of ABCB1 in gedatolisib resistance in canine tumor cells. Oncol Rep. 2022;47(4):61.doi: 10.3892/or.2022.8272
3. Curigilano G, Shapiro GI, Kristeleit RS, et al. A Phase 1B open-label study of gedatolisib (PF-05212384) in combination with other anti-tumour agents for patients with advanced solid tumours and triple-negative breast cancer. BR J Cancer. Published November 5, 2022.doi: 10.1038/s41416-022-02025-9.
