Home › Trials › NCT06757634

Gedatolisib plus fulvestrant and a CDK4/6 inhibitor for first-line HR-positive, HER2-negative advanced breast cancer

VIKTORIA-2: A Randomized, Open-Label, Phase 3 Study of Fulvestrant and CDK4/6 Inhibitors With or Without Gedatolisib as First-Line Treatment in Patients With HR-Positive and HER2-Negative Advanced Breast Cancer

Phase 3 Interventional Celcuity Inc · NCT06757634

This trial tests whether adding intravenous gedatolisib to fulvestrant plus a CDK4/6 inhibitor (palbociclib or ribociclib) helps people with HR+/HER2- advanced or metastatic breast cancer whose disease progressed during or within 12 months after adjuvant endocrine therapy.

Quick facts

PhasePhase 3
Study typeInterventional
Enrollment674 (estimated)
Ages18 Years and up
SexAll
SponsorCelcuity Inc Industry-sponsored
Drugs / interventionschemotherapy
Locations203 sites (Duarte, California and 202 other locations)
Trial IDNCT06757634 on ClinicalTrials.gov

What this trial studies

This is an open-label, randomized Phase 3 trial comparing gedatolisib combined with fulvestrant and a CDK4/6 inhibitor to fulvestrant with a CDK4/6 inhibitor alone as first-line therapy for HR+/HER2- advanced or metastatic breast cancer after early relapse on adjuvant endocrine therapy. Investigators will perform a safety run-in to set the gedatolisib dose with ribociclib, assign participants to cohorts by PIK3CA mutation status, and then randomize within each cohort to the investigational or control arm. Gedatolisib is given intravenously as a pan-PI3K/mTOR inhibitor, while palbociclib or ribociclib are oral CDK4/6 inhibitors and fulvestrant is an intramuscular estrogen receptor degrader. Primary endpoints focus on efficacy and safety compared across arms.

Who should consider this trial

Good fit: Adults (women and men) with histologically confirmed HR+/HER2- locally advanced or metastatic breast cancer whose disease progressed during or within 12 months of adjuvant endocrine therapy, who have not received prior systemic therapy for advanced disease, and who can provide tumor tissue or a liquid biopsy for PIK3CA testing are ideal candidates.

Not a fit: Patients with HER2-positive disease, extensive prior systemic therapy for advanced disease, or contraindications to PI3K/mTOR inhibitors, CDK4/6 inhibitors, or intravenous treatment are unlikely to benefit from this regimen.

Why it matters

Potential benefit: If successful, this combination could extend time without disease progression and delay the need for later therapies in affected patients.

How similar studies have performed: Combining CDK4/6 inhibitors with endocrine therapy is an established effective approach and targeting the PI3K pathway has helped PIK3CA-mutant HR+ disease (for example, alpelisib), but gedatolisib as a pan-PI3K/mTOR agent has had limited phase 3 evidence to date.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

1. Histologically or cytologically confirmed diagnosis of metastatic or locally advanced HR+/HER2- breast cancer
2. Adult females, pre- and/or post-menopausal, and adult males. Pre-menopausal (and peri-menopausal) women can be enrolled if amenable to treatment with an LHRH agonist. Patients are to have commenced concomitant treatment with LHRH agonist prior to or on Cycle 1, Day 1 and must be willing to continue for the duration of the study.
3. Negative pregnancy test for females of childbearing potential. Female subjects who are not surgically sterile must use a medically effective contraceptive method from screening until 2 years after the last dose of study treatment.
4. Progression of disease during or within 12 months of completing (neo)adjuvant ET.
5. Adequate archival, fresh tumor tissue, or liquid biopsy for the analysis of PIK3CA mutational status.
6. Permitted prior therapies:

   1. (neo)adjuvant fulvestrant or any selective ER degrader only if the treatment duration \< 6 months
   2. (neo)adjuvant chemotherapy
   3. (neo)adjuvant CDK4/6 inhibitor, unless PD was on or within 6 months of discontinuation of CDK4/6i
7. Subject has radiologically measurable disease according to RECIST v1.1, per local assessment. Patients with evaluable bone-only disease are not eligible. Patients with bone-only disease that has lytic or mixed lytic/blastic lesions and at least one measurable soft tissue component per RECIST v1.1 may be eligible.
8. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
9. Life expectancy of at least \>6 months.
10. Adequate bone marrow, hepatic, renal and coagulation function.

Exclusion Criteria:

1. Concurrent malignancies other than adequately treated non-melanoma skin cancer. Previous malignancies in remission but curatively treated with no evidence of disease progression and judged by local Investigator to be at low risk of impacting health or survival while on study.
2. Prior treatment with a phosphoinositide 3-kinase (PI3K) inhibitor, a protein kinase B (Akt) inhibitor, or a mechanistic target of rapamycin (mTOR) inhibitor
3. Prior treatment with systemic anticancer therapy for ABC
4. Subjects with type 1 diabetes
5. Known and untreated, or active, brain or leptomeningeal metastases
6. History of clinically significant cardiovascular abnormalities
7. History of drug-induced symptomatic interstitial lung disease (pneumonitis) or hepatitis

Where this trial is running

Duarte, California and 202 other locations

+153 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Breast CancerBreast Cancer, Advanced or MetastaticGedatolisibHR PositiveER PositiveHER2 NegativePIK3CA MTPI3K
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.