Gedatolisib + Fulvestrant +/- Palbociclib for Advanced Breast Cancer

(VIKTORIA-1 Trial)

Recruiting at 240 trial locations

Overseen By Nadene Zack, MS

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Celcuity Inc

Must be taking: LHRH agonists

Must not be taking: PI3K inhibitors, Akt inhibitors

Disqualifiers: Diabetes, Brain metastases, Cardiovascular, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 48 months

701 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness and safety of a combination of medicines for advanced hormone receptor-positive (HR+) and HER2-negative breast cancer. Researchers examine how well gedatolisib (an experimental treatment) and fulvestrant, with or without palbociclib, perform after previous treatments lose effectiveness. Participants receive different drug combinations based on specific genetic mutations in their cancer. Those who have experienced breast cancer progression after using CDK4/6 inhibitors and aromatase inhibitors may be suitable for this trial. Potential participants must have a confirmed diagnosis of HR+/HER2- breast cancer that has spread locally or to other parts of the body. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you must not have had certain treatments like PI3K inhibitors or more than two lines of endocrine therapy for advanced disease.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the combination of gedatolisib and fulvestrant, with or without palbociclib, is generally safe for patients with advanced breast cancer. Patients have found the gedatolisib-fulvestrant combination to be well-tolerated. Studies report that side effects are manageable, and the treatment is effective at the recommended doses.

When combined with both palbociclib and fulvestrant, gedatolisib also demonstrates promising safety results. The response rate, indicating how well the cancer responds to treatment, was encouraging compared to standard treatments. Side effects, such as tiredness and nausea, are similar to those expected from cancer treatments and are generally manageable.

Overall, these treatments have proven safe for patients, with many able to handle the side effects well. This is important for those considering joining a clinical trial, as it suggests that the treatment could be a viable option for managing advanced breast cancer. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for advanced breast cancer because they offer a new approach by targeting the PI3K/mTOR pathway, which is not the focus of many current therapies like hormone therapy or CDK4/6 inhibitors. Gedatolisib, in particular, is a dual inhibitor of both PI3K and mTOR, which could potentially lead to more effective suppression of cancer cell growth. Additionally, when combined with Fulvestrant, and in some cases Palbociclib, this treatment could offer a more comprehensive attack on cancer cells by both inhibiting growth signals and blocking the effects of estrogen, which is often a driver in breast cancer. This combination strategy could provide a new option for patients, especially those with PIK3CA mutations, who may not respond well to existing treatments.

What evidence suggests that this trial's treatments could be effective for advanced breast cancer?

Research has shown that combining gedatolisib and fulvestrant, which participants in this trial may receive, can help treat advanced breast cancer. Studies have found that this combination significantly improves progression-free survival (PFS), meaning patients lived longer without their cancer worsening. In this trial, some participants will receive gedatolisib, palbociclib, and fulvestrant together. Previous studies showed that 85.2% of patients responded positively to this treatment. Additionally, this combination resulted in a median PFS of 9.3 months. These results suggest that this treatment might be more effective than standard therapies for this type of breast cancer. ^{3 6 7 8 9}

Who Is on the Research Team?

Nadene Zack

Principal Investigator

Celcuity Inc

Are You a Good Fit for This Trial?

This trial is for adults with advanced or metastatic HR+/HER2- breast cancer who've progressed after CDK4/6 and aromatase inhibitor therapy. They must have a life expectancy of at least 3 months, ECOG status of 0-1, adequate organ function, and no pregnancy. Pre-menopausal women must agree to LHRH agonist treatment.

Inclusion Criteria

I am a pre/peri-menopausal woman willing to start LHRH agonist treatment.

I can provide a recent or past sample of my tumor for PIK3CA mutation testing.

My blood, liver, kidneys, and clotting functions are all working well.

Exclusion Criteria

Known hypersensitivity to the study drugs or their components

My cancer is only in the bones and does not affect soft tissues.

My cancer has spread to my organs and is causing symptoms that could quickly become life-threatening.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive gedatolisib plus fulvestrant with or without palbociclib based on PIK3CA mutation status

48 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

30 days

What Are the Treatments Tested in This Trial?

Interventions

• Alpelisib
• Fulvestrant
• Gedatolisib
• Palbociclib

Trial Overview The study tests gedatolisib plus fulvestrant with or without palbociclib against standard care in patients whose breast cancer has worsened despite previous treatments. It's an open-label Phase 3 trial where participants are randomly assigned to different drug combinations.

How Is the Trial Designed?

Group I: Arm F - Patients with PIK3CA Mutation (MT) Experimental Treatment 2 Interventions

Gedatolisib + Fulvestrant

Group II: Arm D - Patients with PIK3CA Mutation (MT) Experimental Treatment 3 Interventions

Gedatolisib + Palbociclib + Fulvestrant

Group III: Arm B - Patients Lacking PIK3CA Mutations (WT) Experimental Treatment 2 Interventions

Gedatolisib + Fulvestrant

Group IV: Arm A - Patients Lacking PIK3CA Mutations (WT) Experimental Treatment 3 Interventions

Gedatolisib + Palbociclib + Fulvestrant

Group V: Arm E - Patients with PIK3CA Mutation (MT) Active Control 2 Interventions

Alpelisib + Fulvestrant

Group VI: Arm C - Patients Lacking PIK3CA Mutations (WT) Active Control 1 Intervention

Fulvestrant

Fulvestrant is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Faslodex for:

• Hormone receptor-positive metastatic breast cancer
• Locally advanced breast cancer

Approved in United States as Faslodex for:

• Hormone receptor-positive metastatic breast cancer
• Locally advanced breast cancer

Approved in Canada as Faslodex for:

• Hormone receptor-positive metastatic breast cancer
• Locally advanced breast cancer

Approved in Japan as Faslodex for:

• Hormone receptor-positive metastatic breast cancer
• Locally advanced breast cancer

Who Is Running the Clinical Trial?

Celcuity Inc

Lead Sponsor

Trials

9

Recruited

1,600+

Celcuity, Inc.

Lead Sponsor

Trials

7

Recruited

920+

Published Research Related to This Trial

In a phase II study involving 190 postmenopausal women with hormone receptor-positive, HER2-negative advanced breast cancer, the combination of palbociclib and fulvestrant significantly improved one-year progression-free survival (PFS-1y) rates (83.5% vs. 71.9% for placebo) and median PFS (31.8 months vs. 22.0 months).

While the palbociclib/fulvestrant combination showed better efficacy, it was associated with higher rates of grade 3-4 adverse events, particularly neutropenia (68.1% vs. 0% in the placebo group), indicating a need for careful monitoring of side effects in patients receiving this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized phase II study of fulvestrant plus palbociclib or placebo in endocrine-sensitive, hormone receptor-positive/HER2-advanced breast cancer: GEICAM/2014-12 (FLIPPER). Albanell, J., Martínez, MT., Ramos, M., et al.[2022]

Palbociclib, the first oral CDK4/6 inhibitor, significantly improves median progression-free survival in advanced ER-positive/HER2-negative breast cancer, showing 24.8 months with letrozole compared to 14.5 months with placebo, and 9.2 months with fulvestrant compared to 3.8 months with placebo.

The main side effect of palbociclib is neutropenia, which can be managed through dose adjustments, resulting in a favorable safety profile and delayed deterioration of quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Palbociclib-The First of a New Class of Cell Cycle Inhibitors. Schmidt, M., Sebastian, M.[2018]

Palbociclib, when combined with letrozole or fulvestrant, significantly improves progression-free survival and overall survival in women with hormone receptor-positive (HR+)/HER2-negative advanced breast cancer, based on clinical trials.

The treatment has a manageable tolerability profile, with neutropenia being the most common side effect, and does not negatively impact quality of life, making it a valuable option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Palbociclib in metastatic breast cancer: current evidence and real-life data. Serra, F., Lapidari, P., Quaquarini, E., et al.[2020]

Palbociclib, when combined with fulvestrant, significantly improves progression-free survival in women with hormone receptor-positive, HER2-negative advanced breast cancer, showing a median PFS of 9.5 months compared to 4.6 months with placebo, based on a study of 521 women.

The safety profile of palbociclib includes common adverse reactions such as neutropenia and infections, which were observed in over 20% of patients, confirming its known side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval of Palbociclib in Combination with Fulvestrant for the Treatment of Hormone Receptor-Positive, HER2-Negative Metastatic Breast Cancer. Walker, AJ., Wedam, S., Amiri-Kordestani, L., et al.[2022]

Oral palbociclib is an effective treatment for HR-positive, HER2-negative advanced or metastatic breast cancer, significantly prolonging progression-free survival when used with letrozole or fulvestrant in clinical trials involving postmenopausal women.

The most common side effect was neutropenia, which was manageable and rarely led to serious complications, indicating that palbociclib can be safely administered without significantly compromising its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Palbociclib: A Review in HR-Positive, HER2-Negative, Advanced or Metastatic Breast Cancer. Kim, ES., Scott, LJ.[2022]

In a study of 521 premenopausal and postmenopausal patients with endocrine-resistant metastatic breast cancer, those treated with palbociclib and fulvestrant showed a higher rate of prolonged benefit (29%) compared to those on placebo and fulvestrant (15%).

Long-term responders to palbociclib-fulvestrant tended to have less disease burden at baseline and lower rates of certain mutations, but no specific molecular or clinical factors were identified as predictors of long-term benefit.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predictors of prolonged benefit from palbociclib plus fulvestrant in women with endocrine-resistant hormone receptor-positive/human epidermal growth factor receptor 2-negative metastatic breast cancer in PALOMA-3. Cristofanilli, M., DeMichele, A., Giorgetti, C., et al.[2022]

Fulvestrant was well tolerated and provided clinical benefit to 21% of heavily pre-treated postmenopausal women with advanced breast cancer, with 42% achieving stable disease for at least 12 weeks.

The efficacy of fulvestrant was similar whether given after disease progression or as maintenance therapy, with a median time to progression of 3 months and no significant toxicities reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fulvestrant in heavily pre-treated patients with advanced breast cancer: results from a single compassionate use programme centre. Catania, C., Ascione, G., Adamoli, L., et al.[2018]

Palbociclib, in combination with letrozole, is FDA-approved for treating postmenopausal women with hormone-receptor-positive, HER2-negative advanced breast cancer, showing its efficacy as an initial therapy.

The combination of palbociclib with fulvestrant has been found to provide better outcomes than fulvestrant alone for patients who have previously progressed on endocrine therapy, highlighting its potential in advanced treatment scenarios.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Palbociclib: a first-in-class CDK4/CDK6 inhibitor for the treatment of hormone-receptor positive advanced breast cancer. Lu, J.[2022]

In a study involving 108 premenopausal women with advanced breast cancer, palbociclib combined with fulvestrant and goserelin significantly improved median progression-free survival (PFS) to 9.5 months compared to 5.6 months with placebo, indicating its efficacy in this population.

The treatment was well-tolerated, with common side effects including neutropenia and infections, but it did not interfere with ovarian suppression from goserelin, suggesting it could be a viable option to delay chemotherapy for women with endocrine-resistant disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Palbociclib Combined with Fulvestrant in Premenopausal Women with Advanced Breast Cancer and Prior Progression on Endocrine Therapy: PALOMA-3 Results. Loibl, S., Turner, NC., Ro, J., et al.[2022]

In a study of 54 postmenopausal women with metastatic breast cancer, fulvestrant demonstrated clinical benefit in 38.9% of patients, with a median time to progression of 6.4 months, indicating its efficacy even after multiple prior treatments.

Fulvestrant was well tolerated, with no severe toxicities (grade 3/4) reported, suggesting it is a safe option for patients with advanced breast cancer who have limited treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fulvestrant ('Faslodex') in heavily pretreated postmenopausal patients with advanced breast cancer: single centre clinical experience from the compassionate use programme. Mlineritsch, B., Psenak, O., Mayer, P., et al.[2018]

Citations

1. onclive.com onclive.com/view/gedatolisib-based-regimens-may-advance-pik3ca-wild-type-metastatic-breast-cancer-care

Gedatolisib-Based Regimens May Advance PIK3CA Wild- ... The VIKTORIA-1 study demonstrated a statistically significant improvement in PFS with the triplet combination of gedatolisib plus fulvestrant ...

2. cancernetwork.com cancernetwork.com/view/pam-inhibition-adds-value-in-hr-her2--pik3ca-wild-type-advanced-breast-cancer

PAM Inhibition Adds Value in HR+/HER2- PIK3CA Wild ... Gedatolisib enhanced PFS in advanced breast cancer, showcasing significant benefits when combined with fulvestrant and palbociclib.

3. biospace.com biospace.com/press-releases/detailed-results-from-pik3ca-wild-type-cohort-of-phase-3-viktoria-1-trial-presented-at-2025-esmo-congress-demonstrate-potential-for-gedatolisib-regimens-to-be-practice-changing-for-patients-with-hr-her2-advanced-breast-cancer

Detailed Results from PIK3CA Wild-Type Cohort of Phase ... The gedatolisib doublet reduced the risk of progression or death by 67% versus fulvestrant. The detailed study results were presented at a late ...

4. thelancet.com thelancet.com/journals/lanonc/article/PIIS1470-2045(24)00034-2/abstract

Gedatolisib in combination with palbociclib and endocrine ... Gedatolisib in combination with palbociclib and endocrine therapy in women with hormone receptor-positive, HER2-negative advanced breast cancer: results from ...

5. oncodaily.com oncodaily.com/oncolibrary/viktoria-1-trial

VIKTORIA-1 Trial at ESMO 2025: Gedatolisib Combination ... The VIKTORIA-1 trial shows gedatolisib combinations significantly improve progression-free survival in HR+/HER2- breast cancer after CDK4/6 ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05501886

Gedatolisib Plus Fulvestrant With or Without Palbociclib vs ... This is a Phase 3, open-label, randomized clinical trial evaluating the efficacy and safety of gedatolisib plus fulvestrant with or without palbociclib for the ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9814742/

A Phase 1B open-label study of gedatolisib (PF-05212384) ... Gedatolisib combination therapy showed an acceptable tolerability profile, with clinical activity at the recommended Phase 2 dose in patients with TNBC.

8. targetedonc.com targetedonc.com/view/fda-accepts-gedatolisib-for-real-time-review-in-hr-her2-advanced-breast-cancer

FDA Accepts Gedatolisib for Real-Time Review in HR+/HER2 FDA reviews gedatolisib for advanced breast cancer, showing significant progression-free survival improvements in pivotal VIKTORIA-1 trial.

9. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.TPS1118

A phase 3 study of gedatolisib plus fulvestrant with and ... This Phase 3 multinational clinical trial will evaluate geda and FULwith or without palboin patients with HR+/HER2- ABC previously treated with any CDK4/6i.