Skip to content
Triangle logo TriangleGet started
← Study library

NCT05501886 · CITED IN SOURCE DOCUMENTS

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)

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase
PHASE3
Status at capture
ACTIVE NOT RECRUITING
Registry last update
2026-02-10

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 treatment of patients with locally advanced or metastatic HR+/HER2- breast cancer following progression on or after CDK4/6 and aromatase inhibitor therapy.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

No posted result sections were captured. Registered plans do not establish that a treatment works.

Who could take part
eligibility Criteria
Inclusion Criteria: 1. Histologically or cytologically confirmed diagnosis of metastatic or locally advanced breast cancer 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 on it for the duration of the study. 2. Negative pregnancy test for women of childbearing potential. Female subjects of childbearing potential must use an effective and/or acceptable contraceptive method from screening until 1 year after the last dose of study treatment 3. Confirmed diagnosis of estrogen receptor positive and/or progesterone receptor positive, as per American Society of Clinical Oncology/College of American Pathologists (ASCO-CAP) guidelines (2020), based on most recent tumor biopsy utilizing an assay consistent with local standards 4. Documented HER2 immunohistochemistry (IHC) negative as per ASCO-CAP 2018 guidance 5. Adequate archival or fresh tumor tissue for the analysis of PIK3CA mutational status 6. Subject must have documentation of radiological disease progression on or after the last prior treatment and also have radiologically evaluable disease (measurable and/or non-measurable) according to RECIST v1.1, per local assessment. Subjects with bone only disease must have lytic or mixed lytic/blastic lesions that can be accurately assessed; bone only blastic lesions with no soft tissue component is not allowed. 7. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 8. Life expectancy of at least 3 months 9. Progressed during or after CDK4/6 inhibitor combination treatment with non-steroidal aromatase inhibitor (AI) 10. Adequate bone marrow, hepatic, renal and coagulation function Exclusion Criteria: 1. History of malignancies other than adequately treated non-melanoma skin cancer, curatively treated in situ cancer of the cervix, or other solid tumors curatively treated with no evidence of disease for ≥3 years 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 chemotherapy and antibody drug conjugates for advanced disease is not permitted (prior adjuvant or neoadjuvant chemotherapy is permitted) 4. More than 2 lines of prior endocrine therapy treatment 5. Bone only disease that is only blastic with no soft tissue component 6. Subjects with type 1 diabetes or uncontrolled type 2 diabetes 7. Known and untreated, or active, brain or leptomeningeal metastases a. Subjects with previously treated central nervous system (CNS) metastases may be enrolled in the study if they meet the following criteria: do not require supportive therapy with steroids; do not have seizures and do not exhibit uncontrolled neurological symptoms; stable disease confirmed by radiographic assessment within at least 4 weeks prior to enrollment 8. Patients with advanced, symptomatic, visceral spread that are at risk of life-threatening complication in the short-term 9. History of clinically significant cardiovascular abnormalities such as: Congestive heart failure (New York Heart Association (NYHA) classification ≥ II within 6 months of study entry 1. Myocardial infarction within 12 months of study entry 2. History of any uncontrolled (or untreated) clinically significant cardiac arrhythmias, (e.g., ventricular tachycardia), complete left bundle branch block, high grade AV block (e.g., bifascicular block, Mobitz type II and third degree AV block), supraventricular, nodal arrhythmias, or conduction abnormality in the previous 12 months 3. Uncontrolled hypertension defined by systolic blood pressure (SBP) ≥160 mmHg and/or diastolic blood pressure (DBP) ≥100 mmHg, with or without antihypertensive medication (initiation or adjustment of antihypertensive medication\[s\] is allowed prior to screening) 4. Long QT syndrome, family history of idiopathic sudden death or congenital long QT syndrome, or any of the following: * i. Risk factors for Torsades de Pointes (TdP) including uncorrected hypokalemia or hypomagnesemia, or history of clinically significant/symptomatic bradycardia * ii. On screening, inability to determine the corrected QT interval using Fridericia's formula (QTcF) on the ECG (i.e., unreadable or not interpretable) or QTcF \>480 msec (determined by mean of triplicate ECGs at screening) 10. Known hypersensitivity to the study drugs or their components 11. Pregnant or breast-feeding women 12. Concurrent participation in another interventional clinical trial 1. Subjects must agree not to participate in another clinical trial (other than observational) at any time during participation in VIKTORIA-1.
healthy Volunteers
false
minimum Age
18 Years
sex
ALL
std Ages
  1. ADULT
  2. OLDER_ADULT
Treatment arms and interventions
arm Groups
  1. description
    Gedatolisib + Palbociclib + Fulvestrant
    intervention Names
    1. Drug: Gedatolisib
    2. Drug: Palbociclib
    3. Drug: Fulvestrant
    label
    Arm A - Patients Lacking PIK3CA Mutations (WT)
    type
    EXPERIMENTAL
  2. description
    Gedatolisib + Fulvestrant
    intervention Names
    1. Drug: Gedatolisib
    2. Drug: Fulvestrant
    label
    Arm B - Patients Lacking PIK3CA Mutations (WT)
    type
    EXPERIMENTAL
  3. description
    Fulvestrant
    intervention Names
    1. Drug: Fulvestrant
    label
    Arm C - Patients Lacking PIK3CA Mutations (WT)
    type
    ACTIVE_COMPARATOR
  4. description
    Gedatolisib + Palbociclib + Fulvestrant
    intervention Names
    1. Drug: Gedatolisib
    2. Drug: Palbociclib
    3. Drug: Fulvestrant
    label
    Arm D - Patients with PIK3CA Mutation (MT)
    type
    EXPERIMENTAL
  5. description
    Alpelisib + Fulvestrant
    intervention Names
    1. Drug: Fulvestrant
    2. Drug: Alpelisib
    label
    Arm E - Patients with PIK3CA Mutation (MT)
    type
    ACTIVE_COMPARATOR
  6. description
    Gedatolisib + Fulvestrant
    intervention Names
    1. Drug: Gedatolisib
    2. Drug: Fulvestrant
    label
    Arm F - Patients with PIK3CA Mutation (MT)
    type
    EXPERIMENTAL
interventions
  1. arm Group Labels
    1. Arm A - Patients Lacking PIK3CA Mutations (WT)
    2. Arm B - Patients Lacking PIK3CA Mutations (WT)
    3. Arm D - Patients with PIK3CA Mutation (MT)
    4. Arm F - Patients with PIK3CA Mutation (MT)
    description
    Gedatolisib 180 mg IV given weekly for 3 weeks (Days 1, 8, 15) followed by 1 week off
    name
    Gedatolisib
    other Names
    1. PF-05212384
    2. PKI-587
    type
    DRUG
  2. arm Group Labels
    1. Arm A - Patients Lacking PIK3CA Mutations (WT)
    2. Arm D - Patients with PIK3CA Mutation (MT)
    description
    Palbociclib 125 mg PO given daily for 3 weeks (21 days), followed by 1 week off
    name
    Palbociclib
    other Names
    1. IBRANCE
    2. PD-0332991
    type
    DRUG
  3. arm Group Labels
    1. Arm A - Patients Lacking PIK3CA Mutations (WT)
    2. Arm B - Patients Lacking PIK3CA Mutations (WT)
    3. Arm C - Patients Lacking PIK3CA Mutations (WT)
    4. Arm D - Patients with PIK3CA Mutation (MT)
    5. Arm E - Patients with PIK3CA Mutation (MT)
    6. Arm F - Patients with PIK3CA Mutation (MT)
    description
    Fulvestrant 500 mg IM (2 × 5 mL injections) given every 2 weeks during Cycle 1 (Days 1 and 15), then every 4 weeks beginning with Cycle 2 Day 1
    name
    Fulvestrant
    other Names
    1. Faslodex
    type
    DRUG
  4. arm Group Labels
    1. Arm E - Patients with PIK3CA Mutation (MT)
    description
    Alpelisib 300 mg PO (2 × 150 mg tablets) given daily for 4 weeks (28 days)
    name
    Alpelisib
    other Names
    1. Piqray
    2. Vijoice
    3. BYL719
    type
    DRUG
Study design
allocation
RANDOMIZED
intervention Model
PARALLEL
masking Info
masking
NONE
primary Purpose
TREATMENT
Enrollment
count
701
type
ESTIMATED
Registered outcome plans (not posted results)
primary Outcomes
  1. description
    PFS is defined as the time from randomization to death or the first documented progression, whichever occurs first, confirmed by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria, as determined based on blinded independent central review (BICR)
    measure
    Progression Free Survival (PFS) in Patients with PIK3CA WT and PIK3CA MT Breast Cancer
    time Frame
    Approximately 48 months
secondary Outcomes
  1. description
    OS is defined as the length of time from randomization until the date of death from any cause method, where PFS is defined as the time from randomization to death or the first documented progression, whichever occurs first, confirmed by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria, as determined based on blinded independent central review (BICR)
    measure
    Overall Survival (OS) in Patients with PIK3CA WT and PIK3CA MT Breast Cancer
    time Frame
    From date of randomization to the date of death due to any cause, up to approximately 48 months
  2. description
    Percentage of subjects who achieved an objective response according to RECIST v1.1 criteria (complete response \[CR\] or partial response \[PR\]) as assessed by BICR)
    measure
    Overall Response Rate (ORR) in Patients with PIK3CA WT and PIK3CA MT Breast Cancer
    time Frame
    Up to approximately 48 months
  3. description
    Time from the assessment of initial response (PR or better) to death or first documented disease progression as assessed by BICR, whichever occurs first
    measure
    Duration of Response (DOR) in Patients with PIK3CA WT and PIK3CA MT Breast Cancer
    time Frame
    Up to approximately 48 months
  4. description
    Time form randomization to the first assessment of PR or better as assessed by BICR, whichever comes first
    measure
    Time to Response (TTR) in Patients with PIK3CA WT and PIK3CA MT Breast Cancer
    time Frame
    Up to approximately 48 months
  5. description
    Percentage of subjects with CR, PR, or stable disease (SD) \>24 weeks as assessed by BICR
    measure
    Clinical Benefit Rate (CBR) in Patients with PIK3CA WT and PIK3CA MT Breast Cancer
    time Frame
    Up to approximately 48 months
  6. description
    The FACT-B TOI is an abbreviated (24-item) version of the full FACT-B which focuses only on the patient's Physical Well-being (PWB), Functional Well-being (FWB), and Breast Cancer Subscale (BCS) components using a 5-level scale, (Not at all, A little bit, Some-what, Quite a bit, Very much).
    measure
    Quality of Life (QOL)Functional Assessment of Cancer Therapy - Breast Trial Outcome Index (FACT-B TOI) Questions in Patients with PIK3CA WT and PIK3CA MT Breast Cancer
    time Frame
    From baseline to 30 Day Safety Follow-up
  7. description
    NCCN-FACT is derived from the FACT-B and only 4 additional items will be administered to enable optional scoring of the NFBSI subscales and total score using a 5-level scale (Not at all, A little bit, Some-what, Quite a bit, Very much).
    measure
    Quality of Life (QOL) NCCN-FACT Breast Symptom Index -16 (NFBSI-16) in Patients with PIK3CA WT and PIK3CA MT Breast Cancer
    time Frame
    From baseline to 30 Day Safety Follow-up
  8. description
    Patient-Reported Outcomes Measurement Information System (PROMIS®) Short Form v2.0 - Physical Function 8c using a 5-level scale (Without any difficulty, With a little difficulty, With some difficulty, With much difficulty, Unable to do)
    measure
    Patient-Reported Outcomes in Patients with PIK3CA WT and PIK3CA MT Breast Cancer
    time Frame
    From baseline to 30 Day Safety Follow-up
  9. description
    EuroQol 5 Dimension 5 Level (EQ-5D-5L) - This is a 5 question, self-administered visual analog scale (VAS) where patients use 0 (worst health) to 100 (best health) to indicate how they view their health.
    measure
    EuroQol 5 in Patients with PIK3CA WT and PIK3CA MT Breast Cancer
    time Frame
    From baseline to 30 Day Safety Follow-up
  10. description
    Safety and tolerability will be evaluated by review of type, incidence, severity (as graded by the National Cancer Institute Common Terminology Criteria for Adverse Events \[NCI CTCAE\] v5.0), seriousness, and relationship to study medications of adverse events (AEs) and any laboratory abnormalities
    measure
    Adverse Events
    time Frame
    Up to approximately 48 months
Full study description
brief Summary
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 treatment of patients with locally advanced or metastatic HR+/HER2- breast cancer following progression on or after CDK4/6 and aromatase inhibitor therapy.
detailed Description
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 treatment of patients with advanced (inoperable) or metastatic Hormone Receptor Positive, Human Epidermal Growth Factor Receptor 2 Negative (HR+/HER2-) breast cancer following progression on or after CDK4/6 and aromatase inhibitor therapy. Gedatolisib is an intravenously administered pan-PI3K/mTOR inhibitor. Palbociclib is a CDK4/6 inhibitor. Fulvestrant is a selective estrogen receptor degrader (SERD). Subjects will be assessed for PIK3CA status and then randomized to treatment arms according to their confirmed PIK3CA mutation status.
Source references
references
  1. citation
    Hurvitz SA, Layman RM, Curigliano G, Andre F, Cristofanilli M, Kim SB, Martinez Rodriguez JL, Nadal JC, Kim GM, Lo L, Remolina-Bonilla YA, Rosselli G, Emile G, Korbenfeld E, Puig JM, Wesolowski R, Martin M, Ring A, Han HS, Giordano A, Mutka SC, Moss K, Suzuki S, Sullivan B, Gorbatchevsky I, Pistilli B; VIKTORIA-1 Study Group. 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 Apr 20;44(12):1108-1119. doi: 10.1200/JCO-25-02643. Epub 2026 Mar 9.
    pmid
    41802242
    type
    DERIVED
Source notices and limitations
    Discovery and provenance
    1. release id
      ctgov-registry-7ad944f6deaf1f5cd6122126
      edge id
      nct-edge-8a029a9fc8b0107699b0
      requested nct id
      NCT05501886
      primary nct id
      NCT05501886
      source kind
      fda_approval_notice
      source record id
      fda-cfcc707359fdc22f
      source file sha256
      74217a4030c1a9c546b3aa865934ded1ad916ef10f82fd36f714296469ba8ad2
      payload sha256
      862649463e1a68be862e43135ff748e727a11877dbfe11ae82b5a131ee3d7021
      payload
      clinical indication matching status
      not_inferred
      end exclusive
      true
      id
      nct-edge-8a029a9fc8b0107699b0
      link basis
      explicit_NCT_identifier_in_acquired_source
      nct id
      NCT05501886
      occurrences
      1. context exact
        tps://www.accessdata.fda.gov/scripts/cder/daf/index.cfm">Drugs@FDA</a>.</p><h2>Efficacy and Safety</h2><p>Efficacy was evaluated in&nbsp;Study 1 of VIKTORIA-1 (NCT05501886), an open-label, randomized, multicenter trial that enrolled 392 adults with locally advanced (inoperable) or metastatic HR-positive, HER2-negative breast canc
        end
        25719
        exact text
        NCT05501886
        start
        25708
      offset unit
      unicode_code_points
      source event date
      2026-07-14
      source file
      /tmp/cancer-full-research/updates/pages/fda-approves-gedatolisib-fulvestrant-or-without-palbociclib-hr-positive-her2-negative-locally.html
      source file sha256
      74217a4030c1a9c546b3aa865934ded1ad916ef10f82fd36f714296469ba8ad2
      source json pointer
      Source null
      source kind
      fda_approval_notice
      source record id
      fda-cfcc707359fdc22f
      source string basis
      UTF-8_text_with_universal_newline_translation
      source string sha256
      74217a4030c1a9c546b3aa865934ded1ad916ef10f82fd36f714296469ba8ad2
      source title
      FDA approves gedatolisib with fulvestrant, with or without palbociclib, for HR-positive, HER2-negative locally advanced or metastatic breast cancer

    Preserved source evidence · Not medical advice