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Studie som vurderer effektiviteten og sikkerheten ved behandling med Alpelisib Plus Fulvestrant hos japanske menn og postmenopausale kvinner med avansert brystkreft

17. september 2026 oppdatert av: Novartis Pharmaceuticals

En fase II åpen, 2-delt, multisenterstudie av BYL719 (Alpelisib) i kombinasjon med Fulvestrant for menn og postmenopausale kvinner med PIK3CA mutasjonshormonreseptor (HR) positiv, HER2-negativ, avansert brystkreft som progredierte på eller Etter Aromatase Inhibitor (AI) Behandling i Japan

The purpose of this study is to assess the safety and efficacy of alpelisib plus fulvestrant in men and postmenopausal women with hormone receptor (HR) positive, human epidermal growth factor 2 (HER2)-negative, advanced breast cancer harboring a PIK3CA mutation in Japan, whose disease has progressed on or after aromatase inhibitor (AI) treatment regardless of prior CDK4/6 inhibitor use.

Studieoversikt

Status

Aktiv, ikke rekrutterende

Forhold

Intervensjon / Behandling

Detaljert beskrivelse

This is a Phase II open-label, 2-Part, multi-center study in Japan. The study will be conducted in two parts: Part 1 (Cohort 1) includes participants regardless of prior CDK4/6 inhibitor use and is designed to determine the recommended dose (RD), evaluate the tolerability and safety of alpelisib in combination with fulvestrant. Part 2 consists of 2 cohorts (the CDK4/6 inhibitor naive participants are in Cohort 2 and the CDK4/6 inhibitor pre-treated participants are in Cohort 3) which are designed to assess the efficacy and safety of alpelisib in combination with fulvestrant, will start once the RD of alpelisib is established.

Participants will be treated until disease progression, unacceptable toxicity, death or discontinuation from the study treatment for any other reason and will be followed for survival regardless of treatment discontinuation reason (except if consent is withdrawn or participant is lost to follow up).

Studietype

Intervensjonell

Registrering (Faktiske)

24

Fase

  • Fase 2

Kontakter og plasseringer

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

Studiesteder

  • Japan
      • Niigata, Japan, 951-8566
        • Novartis Investigative Site
    • Aichi-ken
      • Nagoya, Aichi-ken, Japan, 4668560
        • Novartis Investigative Site
      • Nagoya, Aichi-ken, Japan, 4678602
        • Novartis Investigative Site
      • Nagoya, Aichi-ken, Japan, 4648681
        • Novartis Investigative Site
    • Chiba
      • Kashiwa, Chiba, Japan, 2778577
        • Novartis Investigative Site
    • Kanagawa
      • Isehara, Kanagawa, Japan, 2591193
        • Novartis Investigative Site
      • Yokohama, Kanagawa, Japan, 2418515
        • Novartis Investigative Site
    • Kumamoto
      • Kumamoto, Kumamoto, Japan, 8608556
        • Novartis Investigative Site
    • Miyagi
      • Sendai, Miyagi, Japan, 9808574
        • Novartis Investigative Site
    • Osaka
      • Osaka, Osaka, Japan, 5418567
        • Novartis Investigative Site
      • Osaka, Osaka, Japan, 5400006
        • Novartis Investigative Site
      • Suita, Osaka, Japan, 5650871
        • Novartis Investigative Site
    • Tokyo
      • Bunkyo Ku, Tokyo, Japan, 1138677
        • Novartis Investigative Site
      • Koto Ku, Tokyo, Japan, 1358550
        • Novartis Investigative Site
      • Meguro-ku, Tokyo, Japan, 1528902
        • 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

Inclusion Criteria:

  • Japanese man or postmenopausal woman
  • Participant has adequate tumor tissue for the analysis of PIK3CA mutational status by a Novartis designated laboratory.
  • Participant has identified PIK3CA mutation (as determined by a Novartis designated laboratory)
  • 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 (FISH, CISH or SISH) test is required by local laboratory testing
  • Participant has measurable disease, i.e., at least one measurable lesion as per RECIST 1.1
  • Participant has advanced breast cancer
  • Participant has ECOG performance status 0 or 1

Exclusion Criteria:

  • Participant with symptomatic visceral disease or any disease burden that makes the participant ineligible for endocrine therapy per the investigator's best judgment
  • Participant has received prior treatment;
  • with chemotherapy (except for neoadjuvant/ adjuvant chemotherapy), fulvestrant, any PI3K, mTOR or AKT inhibitor for Cohort 1 and 3
  • with chemotherapy (except for neoadjuvant/ adjuvant chemotherapy), fulvestrant, any PI3K, mTOR, AKT inhibitor or CDK 4/6 inhibitor for Cohort 2
  • Participant has a known hypersensitivity to alpelisib or fulvestrant, or to any of the excipients of alpelisib or fulvestrant
  • Participant with inflammatory breast cancer at screening
  • Participant is concurrently using other anti-cancer therapy
  • Participant has had surgery within 14 days prior to starting study drug or has not recovered from major side effects
  • Participant with an established diagnosis at screening of diabetes mellitus type I or not controlled type II (based on FPG and HbA1c)
  • Participant has currently documented pneumonitis /interstitial lung disease
  • History of acute pancreatitis within 1 year of screening or past medical history of chronic pancreatitis
  • Participant with unresolved osteonecrosis of the jaw
  • Participant has a history of severe cutaneous reactions

Other protocol-defined inclusion/exclusion criteria may 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: Ikke-randomisert
  • Intervensjonsmodell: Parallell tildeling
  • Masking: Ingen (Open Label)

Våpen og intervensjoner

Deltakergruppe / Arm
Intervensjon / Behandling
Eksperimentell: Cohort 1:CDK4/6 inhibitor naive or pre-treated (Part 1)

Participants regardless of prior CDK4/6 inhibitor will be treated at escalating doses (200 mg, 250 mg and 300 mg, orally) of BYL719 in combination with Fulvestrant (500 mg, intramuscular).
Legemiddel: Alpelisib

[Part 1] Alpelisib administered at 200 mg (DL 1), 250 mg (DL 2) or 300mg (DL 3) orally once daily on a continuous dosing schedule starting on Cycle 1 Day 1 in a 28 day cycle.

If DL 1 is tolerated, the alpelisib doses of 250 mg will be investigated. If DL 2 is tolerated, the alpelisib doses of 300 mg will be investigated.

[Part 2] In the Part 2, participants will be enrolled into Cohort 2 (CDK4/6 inhibitor naive) and Cohort 3 (CDK4/6 inhibitor pre-treated) in parallel and alpelisib will be administered at the recommended dose identified in Part 1.

Andre navn:
  • BYL719
Legemiddel: Fulvestrant

Fulvestrant is administered at a dose of 500 mg intramuscular on Cycle 1 Day 1, Day 15, and Day 1 of every cycle thereafter (where a cycle is 28 days).

Andre navn:
  • Faslodex
Eksperimentell: Cohort 2: CDK4/6 inhibitor naive (Part 2)

Participants who are CDK4/6 inhibitor naive will be treated with BYL719 at the recommended dose identified in Part 1 in combination with Fulvestrant (500 mg, intramuscular).
Legemiddel: Alpelisib

[Part 1] Alpelisib administered at 200 mg (DL 1), 250 mg (DL 2) or 300mg (DL 3) orally once daily on a continuous dosing schedule starting on Cycle 1 Day 1 in a 28 day cycle.

If DL 1 is tolerated, the alpelisib doses of 250 mg will be investigated. If DL 2 is tolerated, the alpelisib doses of 300 mg will be investigated.

[Part 2] In the Part 2, participants will be enrolled into Cohort 2 (CDK4/6 inhibitor naive) and Cohort 3 (CDK4/6 inhibitor pre-treated) in parallel and alpelisib will be administered at the recommended dose identified in Part 1.

Andre navn:
  • BYL719
Legemiddel: Fulvestrant

Fulvestrant is administered at a dose of 500 mg intramuscular on Cycle 1 Day 1, Day 15, and Day 1 of every cycle thereafter (where a cycle is 28 days).

Andre navn:
  • Faslodex
Eksperimentell: Cohort 3: CDK4/6 inhibitor pre-treated (Part 2)

Participants who are CDK4/6 inhibitor pre-treated will be treated with BYL719 at the recommended dose identified in Part 1 in combination with Fulvestrant (500 mg, intramuscular).
Legemiddel: Alpelisib

[Part 1] Alpelisib administered at 200 mg (DL 1), 250 mg (DL 2) or 300mg (DL 3) orally once daily on a continuous dosing schedule starting on Cycle 1 Day 1 in a 28 day cycle.

If DL 1 is tolerated, the alpelisib doses of 250 mg will be investigated. If DL 2 is tolerated, the alpelisib doses of 300 mg will be investigated.

[Part 2] In the Part 2, participants will be enrolled into Cohort 2 (CDK4/6 inhibitor naive) and Cohort 3 (CDK4/6 inhibitor pre-treated) in parallel and alpelisib will be administered at the recommended dose identified in Part 1.

Andre navn:
  • BYL719
Legemiddel: Fulvestrant

Fulvestrant is administered at a dose of 500 mg intramuscular on Cycle 1 Day 1, Day 15, and Day 1 of every cycle thereafter (where a cycle is 28 days).

Andre navn:
  • Faslodex

Hva måler studien?

Primære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
[Part 1] The incidence of Dose Limiting Toxicities (DLTs) of alpelisib in combination with fulvestrant
Tidsramme: From Cycle 1 Day 1 to Cycle 2 Day 28 (Cycle = 28 days)

A DLT is defined as an AE or abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurs within the first 2 cycles (the first 56 days) of treatment with alpelisib in combination with fulvestrant and meets any of the criteria specified in the protocol .
From Cycle 1 Day 1 to Cycle 2 Day 28 (Cycle = 28 days)
[Part 2] Overall Response Rate (ORR) in CDK4/6 inhibitor naive participants
Tidsramme: Up to approximately 36 months

ORR is defined as the proportion of participants with best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR) based on local investigator assessment per RECIST 1.1.
Up to approximately 36 months

Sekundære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
[Part 1] Number of participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
Tidsramme: Up to approximately 37 months

Safety is determined by incidence, type, and severity of adverse events per CTCAE v4.03 criteria including changes in laboratory values, vital signs, liver assessments, renal and cardiac assessments.
Up to approximately 37 months
[Part 1] Number of participants with dose adjustments
Tidsramme: Up to approximately 37 months

The number of participants with dose adjustments (reductions, interruption, or permanent discontinuation) and the reasons
Up to approximately 37 months
[Part 1] Dose intensity for alpelisib and fulvestrant
Tidsramme: Up to approximately 37 months

The dose intensity (computed as the ratio of actual cumulative dose received and actual duration of exposure) and the relative dose intensity (computed as the ratio of dose intensity and planned dose intensity)
Up to approximately 37 months
[Part 1] Duration of exposure for alpelisib and fulvestrant
Tidsramme: Up to approximately 37 months

The duration of exposure (in months) to alpelisib and fulvestrant
Up to approximately 37 months
[Part 1] Plasma concentrations of alpelisib in combination with fulvestrant
Tidsramme: Cycle 1 Day 8 (pre-dose), 15 (pre-dose, post-dose 1 hour, 3 hours) and Day 1 of Cycles 2, 4, 6, 8 (pre-dose) (Cycle = 28 days)

Summary statistics of alpelisib plasma concentrations by time point and dose level
Cycle 1 Day 8 (pre-dose), 15 (pre-dose, post-dose 1 hour, 3 hours) and Day 1 of Cycles 2, 4, 6, 8 (pre-dose) (Cycle = 28 days)
[Part 2] Overall Response Rate (ORR) for CDK4/6 inhibitor pre-treated participants
Tidsramme: Up to approximately 36 months

ORR is defined as the proportion of participants with best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR) based on local investigator assessment per RECIST 1.1.
Up to approximately 36 months
[Part 2] Progression Free Survival (PFS)
Tidsramme: Up to approximately 36 months

PFS is defined as the time from the date of first administration of study treatment until the date of the first documented progression or death due to any cause. PFS will be assessed based on local investigator assessment per RECIST 1.1.
Up to approximately 36 months
[Part 2] Overall Survival (OS)
Tidsramme: Up to approximately 60 months

OS is defined as the time from date of first administration of study treatment until date of death due to any cause.
Up to approximately 60 months
[Part 2] Clinical Benefit Rate (CBR)
Tidsramme: Up to approximately 36 months

CBR is defined as the proportion of participants with a best overall response of confirmed CR, or confirmed PR, or an overall response of confirmed stable disease (SD), lasting for a duration of at least 24 weeks. CR, PR, and SD are defined based on local investigator assessment per RECIST 1.1.
Up to approximately 36 months
[Part 2] Duration of Response (DOR)
Tidsramme: Up to approximately 36 months

DOR only applies to participants whose best overall response is CR or PR based on local investigator assessment per RECIST 1.1. The start date is the date of first documented response of CR or PR (i.e. the start date of response, not the date when response was confirmed), and the end date is defined as the date of the first documented progression or death due to underlying cancer.
Up to approximately 36 months
[Part 2] Time to Response (TTR)
Tidsramme: Up to approximately 36 months

TTR is defined as the time from the date of first administration of study treatment until the date of the first documented response of either CR or PR, which must be subsequently confirmed (although date of initial response is used, not date of confirmation).
Up to approximately 36 months
[Part 2] Time to definitive deterioration of Eastern Cooperative Oncology Group (ECOG) performance status
Tidsramme: Up to approximately 36 months

Time to definitive deterioration in ECOG performance status is defined as the time from the date of first administration to the date when ECOG performance status has definitively deteriorated by at least one category compared with baseline. Deterioration is considered definitive if there is no subsequent improvement in ECOG performance status back to the baseline category or above.
Up to approximately 36 months
[Part 2] Number of participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
Tidsramme: Up to approximately 37 months

Incidence, type, and severity of adverse events per CTCAE v4.03 criteria including changes in laboratory values, vital signs, liver assessments, renal and cardiac assessments
Up to approximately 37 months
[Part 2] Number of participants with dose adjustments
Tidsramme: Up to approximately 37 months

The number and percentage of participants with dose interruptions and dose reductions
Up to approximately 37 months
[Part 2] Dose intensity for alpelisib and fulvestrant
Tidsramme: Up to approximately 37 months

The dose intensity (computed as the ratio of actual cumulative dose received and actual duration of exposure) and the relative dose intensity (computed as the ratio of dose intensity and planned dose intensity)
Up to approximately 37 months
[Part 2] Duration of exposure for alpelisib and fulvestrant
Tidsramme: Up to approximately 37 months

The duration of exposure (in months) to alpelisib and fulvestrant
Up to approximately 37 months
[Part 2] Plasma concentrations of alpelisib in combination with fulvestrant
Tidsramme: Cycle 1 Day 8 (pre-dose), 15 (pre-dose, post-dose 1 hour, 3 hours) and Day 1 of Cycles 2, 4, 6, 8 (pre-dose) (Cycle= 28 days)

Summary statistics of alpelisib plasma concentrations by time point and dose level
Cycle 1 Day 8 (pre-dose), 15 (pre-dose, post-dose 1 hour, 3 hours) and Day 1 of Cycles 2, 4, 6, 8 (pre-dose) (Cycle= 28 days)

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)

8. januar 2021

Primær fullføring (Antatt)

26. februar 2027

Studiet fullført (Antatt)

27. februar 2027

Datoer for studieregistrering

Først innsendt

19. august 2020

Først innsendt som oppfylte QC-kriteriene

19. august 2020

Først lagt ut (Faktiske)

24. august 2020

Oppdateringer av studieposter

Sist oppdatering lagt ut (Faktiske)

18. september 2026

Siste oppdatering sendt inn som oppfylte QC-kriteriene

17. september 2026

Sist bekreftet

1. september 2026

Mer informasjon

Begreper knyttet til denne studien

Nøkkelord

Ytterligere relevante MeSH-vilkår

Andre studie-ID-numre

  • CBYL719C1201

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

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