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Studie for å vurdere effektiviteten og sikkerheten til Alpelisib Plus Fulvestrant hos deltakere med HR-postitiv (HR+), HER2-negativ, avansert brystkreft etter behandling med en CDK4/6-hemmer og en aromatasehemmer. (EPIK-B5)

28. september 2026 oppdatert av: Novartis Pharmaceuticals

EPIK-B5: En fase III, randomisert, dobbeltblind, placebokontrollert studie av Alpelisib i kombinasjon med Fulvestrant for menn og postmenopausale kvinner med HR-positiv, HER2-negativ avansert brystkreft med en PIK3CA-mutasjon, som utviklet seg på eller etter Aromatasehemmer og en CDK4/6-hemmer

The purpose of this study is to complement Study CBYL719C2301 (SOLAR-1) and obtain more comprehensive data on the efficacy and safety of alpelisib (BYL719) in combination with fulvestrant compared with placebo plus fulvestrant in men or postmenopausal women with HR-positive, HER2-negative advanced breast cancer with a PIK3CA mutation who progressed or relapsed on or after treatment with an AI plus a CDK4/6 inhibitor.

Studieoversikt

Status

Aktiv, ikke rekrutterende

Forhold

Intervensjon / Behandling

Detaljert beskrivelse

This is a Phase III, randomized, double-blind, placebo-controlled, international, multi-center trial. Men and postmenopausal women will be randomized to either alpelisib plus fulvestrant or alpelisib-matching placebo plus fulvestrant. Randomization will follow a 1:1 randomization ratio and be stratified by presence of lung and/or liver metastases (yes vs. no) and setting at last prior CDK4/6 inhibitor therapy (adjuvant vs metastatic).

Study treatment with alpelisib plus fulvestrant or alpelisib-matching placebo plus fulvestrant will be initiated on Cycle 1 Day 1, and will continue until disease progression per RECIST v1.1 as per BIRC assessment, start of new antineoplastic therapy, death, lost to follow-up, or withdrawal of consent. A cycle is defined as 28 days.

Studietype

Intervensjonell

Registrering (Faktiske)

210

Fase

  • Fase 3

Kontakter og plasseringer

Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.

Studiesteder

  • Belgia
      • Brussels, Belgia, 1200
        • Novartis Investigative Site
      • Brussels, Belgia, 1000
        • Novartis Investigative Site
      • Ghent, Belgia, 9000
        • Novartis Investigative Site
      • Leuven, Belgia, 3000
        • Novartis Investigative Site
      • Liège, Belgia, 4000
        • Novartis Investigative Site
    • Oost Vlaanderen
      • Sint-Niklaas, Oost Vlaanderen, Belgia, 9100
        • Novartis Investigative Site
  • Bulgaria
      • Plovdiv, Bulgaria, 4004
        • Novartis Investigative Site
      • Sofia, Bulgaria, 1330
        • Novartis Investigative Site
  • Canada
    • Alberta
      • Calgary, Alberta, Canada, T2N 5G2
        • Novartis Investigative Site
    • Ontario
      • Ottawa, Ontario, Canada, K1H 8L6
        • Novartis Investigative Site
  • Danmark
      • Aalborg, Danmark, 9000
        • Novartis Investigative Site
  • Finland
      • Helsinki, Finland, 00029
        • Novartis Investigative Site
      • Tampere, Finland, 33521
        • Novartis Investigative Site
  • Frankrike
      • Besançon, Frankrike, 25030
        • Novartis Investigative Site
      • Clermont-Ferrand, Frankrike, 63011
        • Novartis Investigative Site
      • La Roche-sur-Yon, Frankrike, 85925
        • Novartis Investigative Site
      • Lyon, Frankrike, 69373
        • Novartis Investigative Site
      • Marseille, Frankrike, 13273
        • Novartis Investigative Site
      • Montpellier, Frankrike, 34298
        • Novartis Investigative Site
      • Paris, Frankrike, 75970
        • Novartis Investigative Site
      • Paris, Frankrike, 75475
        • Novartis Investigative Site
      • Valenciennes, Frankrike, 59300
        • Novartis Investigative Site
  • Hellas
      • Athens, Hellas, 115 22
        • Novartis Investigative Site
      • Pátrai, Hellas, 265 04
        • Novartis Investigative Site
  • Irland
      • Dublin, Irland, D04 T6F4
        • Novartis Investigative Site
  • Italia
      • Naples, Italia, 80131
        • Novartis Investigative Site
    • BA
      • Bari, BA, Italia, 70124
        • Novartis Investigative Site
    • BG
      • Bergamo, BG, Italia, 24127
        • Novartis Investigative Site
    • BO
      • Bologna, BO, Italia, 40138
        • Novartis Investigative Site
    • FI
      • Florence, FI, Italia, 50134
        • Novartis Investigative Site
    • GE
      • Genova, GE, Italia, 16132
        • Novartis Investigative Site
    • MI
      • Milan, MI, Italia, 20133
        • Novartis Investigative Site
      • Milan, MI, Italia, 20141
        • Novartis Investigative Site
      • Milan, MI, Italia, 20132
        • Novartis Investigative Site
      • Rozzano, MI, Italia, 20089
        • Novartis Investigative Site
    • PA
      • Palermo, PA, Italia, 90127
        • Novartis Investigative Site
    • PD
      • Padova, PD, Italia, 35128
        • Novartis Investigative Site
    • PN
      • Aviano, PN, Italia, 33081
        • Novartis Investigative Site
    • RM
      • Roma, RM, Italia, 00168
        • Novartis Investigative Site
    • TR
      • Terni, TR, Italia, 05100
        • Novartis Investigative Site
  • Polen
      • Bydgoszcz, Polen, 85-796
        • Novartis Investigative Site
  • Portugal
      • Coimbra, Portugal, 3000-075
        • Novartis Investigative Site
      • Lisbon, Portugal, 1400-038
        • Novartis Investigative Site
      • Lisbon, Portugal, 1099-023
        • Novartis Investigative Site
      • Porto, Portugal, 4200-072
        • Novartis Investigative Site
  • Romania
    • Cluj
      • Floreşti, Cluj, Romania, 407280
        • Novartis Investigative Site
  • Slovakia
      • Bratislava, Slovakia, 812 50
        • Novartis Investigative Site
      • Bratislava, Slovakia, 833 10
        • Novartis Investigative Site
      • Košice, Slovakia, 041 91
        • Novartis Investigative Site
  • Spania
      • A Coruña, Spania, 15009
        • Novartis Investigative Site
      • Barcelona, Spania, 08036
        • Novartis Investigative Site
      • Madrid, Spania, 28040
        • Novartis Investigative Site
      • Málaga, Spania, 29011
        • Novartis Investigative Site
      • Zaragoza, Spania, 50009
        • Novartis Investigative Site
    • Extremadura
      • Badajoz, Extremadura, Spania, 06080
        • Novartis Investigative Site
    • Madrid
      • Pozuelo de Alarcón, Madrid, Spania, 28223
        • Novartis Investigative Site
    • Principality of Asturias
      • Oviedo, Principality of Asturias, Spania, 33011
        • Novartis Investigative Site
  • Tsjekkia
      • Brno, Tsjekkia, 656 53
        • Novartis Investigative Site
      • Nový Jičín, Tsjekkia, 741 01
        • Novartis Investigative Site
      • Prague, Tsjekkia, 128 08
        • Novartis Investigative Site
      • Prague, Tsjekkia, 100 34
        • Novartis Investigative Site
      • Prague, Tsjekkia, 140 59
        • Novartis Investigative Site
  • Tyskland
      • Augsburg, Tyskland, 86150
        • Novartis Investigative Site
      • Berlin, Tyskland, 13353
        • Novartis Investigative Site
      • Essen, Tyskland, 45136
        • Novartis Investigative Site
      • Lübeck, Tyskland, 23538
        • Novartis Investigative Site
    • North Rhine-Westphalia
      • Cologne, North Rhine-Westphalia, Tyskland, 50937
        • Novartis Investigative Site
  • Ungarn
      • Budapest, Ungarn, 1122
        • Novartis Investigative Site

Deltakelseskriterier

Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.

Kvalifikasjonskriterier

Alder som er kvalifisert for studier

18 år til 100 år (Voksen, Eldre voksen)

Tar imot friske frivillige

Nei

Kjønn som er kvalifisert for studier

Alle

Beskrivelse

Key Inclusion Criteria:

  • Participant is an adult ≥ 18 years old at the time of informed consent and has signed informed consent before any trial related activities and according to local guidelines.
  • Participant has a histologically and/or cytologically confirmed diagnosis of ER+ and/or PgR+ breast cancer by local laboratory.
  • Participant has HER2-negative breast cancer defined as a negative in situ hybridization test or an IHC status of 0, 1+ or 2+. If IHC is 2+, a negative in situ hybridization (Fluorescent in situ hybridization (FISH), Chromogenic in situ hybridization (CISH), or Silver-enhanced in situ hybridization (SISH)) test is required by local laboratory testing.
  • Participant has at least one measurable lesion as per RECIST v1.1 criteria as assessed by Investigator (a lesion at a previously irradiated site may only be counted as a target lesion if there is clear sign of progression since the irradiation).
  • Participant has recurrence or progression of disease during or after combined AI (i.e. letrozole, anastrozole, exemestane) and CDK4/6 inhibitor therapy. The combined AI and CDK4/6 inhibitor therapy does not need to be the latest treatment regimen (including adjuvant setting).
  • Participant has received ≤ 2 prior lines of systemic therapies overall in the metastatic setting, of which a maximum of 1 line of prior treatment with chemotherapy (except for neoadjuvant/ adjuvant chemotherapy) is permitted.
  • The presence of PIK3CA mutation(s) determined in tumor tissue prior to enrollment either by a Novartis designated laboratory or in tumor tissue or plasma ctDNA by a local laboratory using a Food and Drug Administration (FDA)-approved PIK3CA Companion Diagnostics (CDx) test for alpelisib or the CE-IVD QIAGEN Therascreen® PIK3CA RGQ PCR test.
  • If female, then the participant must be in postmenopausal status.

Key Exclusion Criteria:

  • Participant with symptomatic visceral disease or any disease burden that makes the participant ineligible for endocrine therapy (ET) per the Investigator's best judgment.
  • Participant who relapsed with documented evidence of progression more than 12 months from completion of (neo)adjuvant endocrine/endocrine-based therapy with no treatment for metastatic disease.
  • Participant has received prior treatment with fulvestrant, any oral selective estrogen receptor degrader (SERD), any Phosphatidylinositol-3-Kinase (PI3K), mammalian Target of Rapamycin (mTOR) or Protein Kinase B (AKT) inhibitor.

Other Inclusion and Exclusion Criteria do apply

Studieplan

Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.

Hvordan er studiet utformet?

Designdetaljer

  • Primært formål: Behandling
  • Tildeling: Randomisert
  • Intervensjonsmodell: Crossover-oppdrag
  • Masking: Trippel

Våpen og intervensjoner

Deltakergruppe / Arm
Intervensjon / Behandling
Eksperimentell: Alpelisib plus fulvestrant

Alpelisib 300 mg orally once daily on a continuous dosing schedule, in a 28-day cycle + fulvestrant 500 mg as intramuscular injection on Cycle 1 Day 1 and 15, and on Day 1 on every Cycle thereafter, in a 28 days cycle.
Legemiddel: Alpelisib

Alpelisib (tablets) administered at 300mg orally once daily on a continuous dosing schedule starting on Cycle 1 Day 1 in a 28 day cycle.

Legemiddel: Fulvestrant

Fulvestrant (prefilled syringe) 500mg administered intramuscularly at Cycle 1 Day 1 and 15 and then at Day 1 of each subsequent cycle (each cycle is 28 days).
Placebo komparator: Alpelisib-matching placebo plus fulvestrant

Alpelisib-matching placebo orally once daily on a continuous dosing schedule, in a 28-day cycle + fulvestrant 500 mg as intramuscular injection on Cycle 1 Day 1 and 15 and on Day 1 on every Cycle thereafter, in a 28 days cycle.

After Protocol Amendment 5 is implemented, alpelisib matching-placebo will no longer be supplied or administered once participants have been unblinded.
Legemiddel: Fulvestrant

Fulvestrant (prefilled syringe) 500mg administered intramuscularly at Cycle 1 Day 1 and 15 and then at Day 1 of each subsequent cycle (each cycle is 28 days).

Legemiddel: Alpelisib-matching placebo

Alpelisib-matching placebo (tablets) administered orally once daily on a continuous dosing schedule starting on Cycle 1 Day 1 in a 28 day cycle.

After Protocol Amendment 5 is implemented, alpelisib matching-placebo will no longer be supplied or administered once participants have been unblinded.

Hva måler studien?

Primære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Progression-free survival (PFS) based on BIRC assessments and using RECIST v1.1 criteria
Tidsramme: From randomization to date of the first documented progression or death due to any cause, assessed up to a maximum duration of 60 months.

Progression-free survival (PFS) is defined as the time from the date of randomization to the date of the first documented progression or death due to any cause. PFS will be assessed by the Blinded Independent Review Committee (BIRC) according to RECIST 1.1.
From randomization to date of the first documented progression or death due to any cause, assessed up to a maximum duration of 60 months.

Sekundære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Overall survival (OS)
Tidsramme: From the date of randomization to the date of death up to a maximum duration of 60 months

Overall survival (OS) is defined as the time from randomization to the date of death due to any cause
From the date of randomization to the date of death up to a maximum duration of 60 months
Overall response rate (ORR) with confirmed response based on BIRC assessments and using RECIST v1.1 criteria
Tidsramme: From the date of randomization up to a maximum duration of 60 months

Overall response rate (ORR) with confirmed response is defined as the proportion of participants with best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR), as per BIRC and according to RECIST 1.1
From the date of randomization up to a maximum duration of 60 months
Clinical benefit rate (CBR) with confirmed response based on BIRC assessments and using RECIST v1.1 criteria
Tidsramme: From the date of randomization up to a maximum duration of 60 months

Clinical benefit rate (CBR) with confirmed response is defined as the proportion of participants with a best overall response of confirmed CR or PR, or SD lasting for a duration of at least 24 weeks. CR, PR and SD are defined as per BIRC review according to RECIST 1.1
From the date of randomization up to a maximum duration of 60 months
Duration of response (DOR) with confirmed response based on BIRC assessments and using RECIST v1.1 criteria
Tidsramme: From first documented response to the date of first progression or deaths, up to a maximum duration of 60 months

Duration of response (DOR) with confirmed response only applies to participants whose best overall response is confirmed complete response (CR) or confirmed partial response (PR) according to RECIST 1.1 based on tumor response data per BIRC review. The start date is the date of first documented response of CR or PR and the end date is defined as the date of the first documented progression or death due to underlying cancer.
From first documented response to the date of first progression or deaths, up to a maximum duration of 60 months
Time to response (TTR) based on BIRC assessments and using RECIST v1.1 criteria
Tidsramme: From the date of randomization to the first documented response up to a maximum duration of 60 months

Time to response (TTR) is defined as the time from the date of randomization to the first documented response of either complete response (CR) or partial response (PR), which must be subsequently confirmed. CR and PR are based on tumor response data as per BIRC review and according to RECIST 1.1
From the date of randomization to the first documented response up to a maximum duration of 60 months
PFS based on BIRC assessment and using RECIST v1.1 criteria for participants by PIK3CA mutation status
Tidsramme: From the date of randomization up to a maximum duration of 60 months

Progression-free survival (PFS) is defined as the time from the date of randomization to the date of the first documented progression or death due to any cause. PFS will be assessed by the Blinded Independent Review Committee (BIRC) according to RECIST 1.1. Results will be presented by PIK3CA mutation status measured in circulating tumor deoxyribonucleic acid (ctDNA) collected at baseline.
From the date of randomization up to a maximum duration of 60 months
Time to definitive deterioration of Eastern Cooperative Oncology Group (ECOG) performance status (PS) from baseline
Tidsramme: From the date of randomization up to maximum duration of 60 months

Time to definitive deterioration of Eastern Cooperative Oncology Group (ECOG) performance status (PS) from baseline is defined as the time from the date of randomization to the date when ECOG PS has definitively worsened by at least one category compared to baseline. Deterioration is considered definitive if there is no subsequent improvement in ECOG PS back to the baseline category or better.
From the date of randomization up to maximum duration of 60 months
Time to definitive (10%) deterioration in the global health status/Quality of Life (QoL) and symptom scale scores of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire 30-item Core Module (EORTC QLQ-C30)
Tidsramme: From the date of randomization up to maximum duration of 60 months

Time to definitive (10%) deterioration in global health status/Quality of Life (QoL) and symptom scale scores of the EORTC QLQ-C30 is defined as the time from the date of randomization to the date of the first occurrence of at least a 10% worsening from baseline in the global health status/QoL or symptom scale scores, with no subsequent improvement above this threshold during treatment or until death from any cause. The EORTC QLQ-C30 is a validated questionnaire assessing cancer patients' quality of life over the past week, comprising 30 items across 5 functional scales, 3 symptom scales, 6 single items, and a global health status/QoL scale. Scores range from 0 to 100, with higher scores indicating a higher response level.
From the date of randomization up to maximum duration of 60 months
Change from baseline in global health status/QoL and symptom scale scores of the EORTC QLQ-C30
Tidsramme: From the date of randomization up to maximum duration of 60 months

Change from baseline in global health status/Quality of Life (QoL) and symptom scale scores of the EORTC QLQ-C30 refers to the variation in scores from baseline across domain scores, health states, overall health status, and index values at each assessment timepoint. The EORTC QLQ-C30 is a validated questionnaire designed to assess the quality of life of cancer patients over the past week. It includes 30 items comprising 5 functional scales, 3 symptom scales, 6 single items, and a global health status/QoL scale. Each scale and item is scored from 0 to 100, with higher scores indicating a higher response level.
From the date of randomization up to maximum duration of 60 months
Time from randomization to objective tumour progression on next line treatment or death from any cause (PFS2)
Tidsramme: From the date of randomization up to maximum duration of 60 months

Time from randomization to objective tumor progression on next-line treatment or death from any cause (PFS2) is defined as the time from the date of randomization to the earliest occurrence of either documented disease progression on next-line therapy, as assessed by the investigator, or death from any cause.
From the date of randomization up to maximum duration of 60 months

Samarbeidspartnere og etterforskere

Det er her du vil finne personer og organisasjoner som er involvert i denne studien.

Sponsor

Novartis Pharmaceuticals

Etterforskere

  • Studieleder: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Studierekorddatoer

Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.

Studer hoveddatoer

Studiestart (Faktiske)

17. desember 2021

Primær fullføring (Antatt)

28. januar 2027

Studiet fullført (Antatt)

26. februar 2027

Datoer for studieregistrering

Først innsendt

1. september 2021

Først innsendt som oppfylte QC-kriteriene

1. september 2021

Først lagt ut (Faktiske)

9. september 2021

Oppdateringer av studieposter

Sist oppdatering lagt ut (Faktiske)

29. september 2026

Siste oppdatering sendt inn som oppfylte QC-kriteriene

28. september 2026

Sist bekreftet

1. september 2026

Mer informasjon

Begreper knyttet til denne studien

Nøkkelord

Ytterligere relevante MeSH-vilkår

Andre studie-ID-numre

  • CBYL719C2303
  • 2023-509133-39-00 (Registeridentifikator: CTIS (EU))
  • 2023 (U.S. NIH-stipend/kontrakt)

Plan for individuelle deltakerdata (IPD)

Planlegger du å dele individuelle deltakerdata (IPD)?

JA

IPD-planbeskrivelse

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Legemiddel- og utstyrsinformasjon, studiedokumenter

Studerer et amerikansk FDA-regulert medikamentprodukt

Nei

Studerer et amerikansk FDA-regulert enhetsprodukt

Nei

Denne informasjonen ble hentet direkte fra nettstedet clinicaltrials.gov uten noen endringer. Hvis du har noen forespørsler om å endre, fjerne eller oppdatere studiedetaljene dine, vennligst kontakt register@clinicaltrials.gov. Så snart en endring er implementert på clinicaltrials.gov, vil denne også bli oppdatert automatisk på nettstedet vårt. .

Abonnere