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Advanced HER2+Breast CancerPhase 3EPIK-B2NCT04208178

Study of Alpelisib (BYL719) in Combination With Trastuzumab and Pertuzumab as Maintenance Therapy in Patients With HER2-positive Advanced Breast Cancer With a PIK3CA Mutation

A Phase 3 study testing Alpelisib, Trastuzumab and Pertuzumab in people with Advanced HER2+Breast Cancer, run by Novartis Pharmaceuticals at 11 sites in 7 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

The purpose of this two part multicenter, randomized, double-blind, placebo-controlled, Phase III study is to evaluate the efficacy and safety of alpelisib compared to alpelisib matching-placebo in combination with trastuzumab and pertuzumab as maintenance treatment of patients with HER2-positive advanced breast… Read more about this study

Who is it for?
Ages 18 to 100 years
Conditions the study is for
Advanced HER2+Breast Cancer
What is being tested?
Alpelisib, Trastuzumab and Pertuzumab
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
19 participants
Where
11 sitesin 7 countries
Study dates
16 Jul 2020to 26 Feb 2027
Phase
Phase 3
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 100 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Participant has histologically-confirmed HER2-positive breast cancer that is advanced (loco-regionally not amenable to surgery or is metastatic).
  • Participant has received pre-study induction therapy with up to and including a maximum of 8 cycles of a taxane (docetaxel, paclitaxel, or nab-paclitaxel), plus trastuzumab and pertuzumab. 4 or 5 cycles of induction therapy are permitted if discontinuation of taxane was due to taxane toxicity. Of note, participants enrolled in Part 1 of this study received 4-6 cycles of pre-study induction therapy.
  • Participant has an Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
  • Participant has adequate bone marrow and organ function
  • Applies only to Part 2: Participant has a PIK3CA mutation(s) present in tumor prior to enrollment, locally confirmed per test listed in protocol or as determined by a Novartis designated central laboratory.

Who cannot join

  • Participant with inflammatory breast cancer at screening.
  • Participant with evidence of disease progression during the pre-study induction therapy and prior to first dose of alpelisib (or alpelisib/alpelisib matching-placebo for Part 2)
  • Participant with an established diagnosis of diabetes mellitus type I or uncontrolled type II based on fasting plasma glucose (FPG) and HbA1c.
  • Participant has a known history of acute pancreatitis within 1 year of screening or past medical history of chronic pancreatitis
  • Participant has clinically significant, uncontrolled heart disease and/or recent cardiac events
  • Participant has a history of Steven-Johnson Syndrome (SJS), erythema multiforme (EM) or Toxic Epidermal Necrolysis (TEN).
  • Participant has currently documented pneumonitis/interstitial lung disease
  • Other protocol-defined Inclusion/Exclusion may apply.

Trial locations and contacts

11 sites in 7 countries.

11 sites in 7 countries

United States2 sites

  • Highlands Oncology Group

    Fayetteville, Arkansas, 72703

  • University of California LA

    Los Angeles, California, 90095

Other trials in United States

Belgium2 sites

  • Novartis Investigative Site

    Leuven, 3000

  • Novartis Investigative Site

    Liège, 4000

Other trials in Belgium

China2 sites

  • Novartis Investigative Site

    Changchun, Jilin, 130021

  • Novartis Investigative Site

    Shanghai, 200032

Other trials in China

France2 sites

  • Novartis Investigative Site

    Saint-Cloud, Hauts De Seine, 92210

  • Novartis Investigative Site

    Saint-Herblain, 44805

Other trials in France

Italy1 site

  • Novartis Investigative Site

    Florence, FI, 50134

Other trials in Italy

Malaysia1 site

  • Novartis Investigative Site

    Kuala Lumpur, 59100

Other trials in Malaysia

Spain1 site

  • Novartis Investigative Site

    L'Hospitalet de Llobregat, Barcelona, 08907

Other trials in Spain

About this study

Official title: EPIK-B2: A Two Part, Phase III, Multicenter, Randomized (1:1), Double-blind, Placebo-controlled Study to Assess the Efficacy and Safety of Alpelisib (BYL719) in Combination With Trastuzumab and Pertuzumab as Maintenance Therapy in Patients With HER2-positive Advanced Breast Cancer With a PIK3CA Mutation

The purpose of this two part multicenter, randomized, double-blind, placebo-controlled, Phase III study is to evaluate the efficacy and safety of alpelisib compared to alpelisib matching-placebo in combination with trastuzumab and pertuzumab as maintenance treatment of patients with HER2-positive advanced breast cancer whose tumor harbors a PIK3CA mutation following induction therapy with a taxane in combination with trastuzumab and pertuzumab. Part 1 is the open-label, safety run-in part of the study, designed to confirm the recommended phase 3 dose (RP3D) dose of alpelisib in combination with trastuzumab and pertuzumab. Following Part 1, Part 2 will be initiated, which is the randomized, Phase III part of the study.

Read the detailed description

The recruitment for this study was permanently halted as of 07-Dec-2022 with the intent of ending the study early because of the evolving treatment landscape and changing paradigms for HER-2 positive BC therapy. This decision was not triggered by any new or unexpected safety findings. Participants in Part 1 will be allowed to continue study treatment (alpelisib in combination with trastuzumab and pertuzumab) if they are deriving clinical benefit as assessed by the investigator and after discussion with the participant and documentation in the medical record. All participants in Part 2 will be unblinded for knowledge of treatment allocation and continuity treatment planning.Participants in the experimental arm will be allowed to continue alpelisib in combination with trastuzumab and pertuzumab based on investigator's judgement and benefit/risk assessment.Participants in Part 2 who are still receiving study treatment in the control arm with alpelisib matching-placebo will not be allowed cross-over to the experimental arm. These participants will be allowed to continue on trastuzumab and pertuzumab if they are deriving clinical benefit as assessed by the investigator and after discussion with the participant and documentation in the medical record.

Being tested
Alpelisib, Alpelisib matching Placebo, Trastuzumab, Pertuzumab
Keywords
BYL719, alpelisib, Advance Breast Cancer, maintenance, HER2 positive, induction, PI3K, Trastuzumab, Pertuzumab

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AlpelisibDrug

    Also called BYL719

    Alpelisib orally taken - continuous once daily, in a 21-day cycle.

  • Alpelisib matching PlaceboDrug

    Alpelisib matching placebo orally taken - continuous once daily, in a 21-day cycle

  • TrastuzumabDrug

    Trastuzumab 6mg/kg given intravenously - Day 1 of Cycle 1, and on Day 1 of every cycle thereafter (Cycle=21 days)

  • PertuzumabDrug

    Pertuzumab 420 mg given intravenously - Day 1 of Cycle 1, and on Day 1 of every cycle thereafter (Cycle=21 days)

Study groups in NCT04208178
Study groupRoleWhat they receive
Part 1: Alpelisib + Trastuzumab + PertuzumabExperimentalIn the Part 1, up to 3 alpelisib dose levels may be sequentially tested in 3 cohorts of subjects: Cohort A: Alpelisib 300mg + trastuzumab (6mg/kg) + pertuzumab (420 mg) Cohort B: Alpelisib 250 mg+ trastuzumab (6mg/kg) + pertuzumab (420 mg) Cohort C: Alpelisib 200mg + trastuzumab (6mg/kg) + pertuzumab (420 mg)
Receives: Drug: Alpelisib; Drug: Trastuzumab; Drug: Pertuzumab
Part 2: Alpelisib + Trastuzumab + PertuzumabExperimentalTrastuzumab (6mg/kg) + pertuzumab (420 mg) in combination with 200mg alpelisib, with potential for intra-participant dose escalation to 250 mg
Receives: Drug: Alpelisib; Drug: Trastuzumab; Drug: Pertuzumab
Part 2: Alpelisib matching Placebo + Trastuzumab + PertuzumabPlacebo comparatorTrastuzumab (6mg/kg) + pertuzumab (420 mg) in combination with 200 mg alpelisib matching placebo, with potential for intra-participant dose escalation to 250 mg
Receives: Drug: Alpelisib matching Placebo; Drug: Trastuzumab; Drug: Pertuzumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Part 1: Incidence of dose limiting toxicities (DLTs) for each dose level

    Incidence of DLTs during the first 6 weeks of treatment for each dose level associated with administration of alpelisib in combination with trastuzumab and pertuzumab

    Measured: 6 weeks

  2. Part 2: Progression Free Survival (PFS)

    PFS is the time from date of randomization/start of treatment to the date of event defined as the first documented progression or death due to any cause. PFS is based on local investigator assessment and using RECIST 1.1 criteria

    Measured: Up to approximately 38 months

Secondary outcomes (11)

  1. Part 1: Alpelisib concentrations by timepoint and dose level

    Characterize exposure of alpelisib when administered in combination with trastuzumab and pertuzumab

    Measured: Day 8 of Cycle 1 and then Day 1 of Cycle 2, Cycle 4, Cycle 6 and Cycle 10 (Cycle = 21 days)

  2. Part 2: Overall survival (OS) (Key Secondary)

    OS is defined as the time from date of randomization to date of death due to any cause

    Measured: Up to approximately 70 months

  3. Part 2: Summary statistics of alpelisib concentrations by timepoint and dose level

    Characterize exposure of alpelisib when administered in combination with trastuzumab and pertuzumab

    Measured: Day 8 of Cycle 1 and then Day 1 of Cycle 2, Cycle 4, Cycle 6 and Cycle 10 (Cycle = 21 days)

  4. Part 2: Overall response rate (ORR) with confirmed response

    ORR is defined as the percentage of patients with best overall response of complete response (CR) or partial response (PR) based on local investigator's assessment according to RECIST 1.1.

    Measured: Up to approximately 38 months

  5. Part 2: Clinical Benefit Rate (CBR) with confirmed response

    Clinical benefit rate is defined as the percentage of patients with a best overall response of complete response (CR) or partial response (PR) or Stable disease (SD) or Non-CR/Non-progressive disease (PD) lasting more than 24 weeks based on local investigator assessment.

    Measured: Up to approximately 38 months

  6. Part 2: Time to response (TTR) based on local radiology assessments

    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 (although date of initial response is used, not date of confirmation). TTR will be assessed using RESIST 1.1 criteria.

    Measured: Up to approximately 38 months

  7. Part 2: Duration of response (DOR) with confirmed response

    DOR is calculated as the time from the date of first documented response (complete response (CR) or partial response (PR)) to the first documented date of progression or death due to underlying cancer.

    Measured: Up to approximately 38 months

  8. Part 2: Change in Functional Assessment of Cancer Therapy - Breast (FACT-B) treatment outcomes index (TOI) from baseline

    The FACT-B is a 37-item instrument designed to measure five domains of Health-Related Quality of Life (HRQOL) in breast cancer patients: Physical Well-being (PWB), Social/family Well-being (SWB), Emotional Well-being (EWB), Functional Well-being (FWB) as well as a Breast Cancer Subscale (BCS).

    The FACT-B TOI is a composite of PWB, FWB and BCS scores. Total score ranges from 0 to 96. Higher FACT-B TOI scores represent better QoL.

    Change from baseline in FACT-B TOI scores will be calculated

    Measured: Baseline, up to approximately 38 months

  9. Part 2: Time to deterioration in FACT-B TOI (defined as a ≥ 5 point decrease from baseline)

    The FACT-B is a 37-item instrument designed to measure five domains of Health-Related Quality of Life (HRQOL) in breast cancer patients: Physical Well-being (PWB), Social/family Well-being (SWB), Emotional Well-being (EWB), Functional Well-being (FWB) as well as a Breast Cancer Subscale (BCS).

    The FACT-B TOI is a composite of PWB, FWB and BCS scores. Total score ranges from 0 to 96. Higher FACT-B TOI scores represent better QoL. Definitive deterioration is defined as the time from the date of randomization to the date of event defined as at least 5-point worsening from baseline with no later improvement above this threshold observed during the course of the treatment or until death due to any cause in FACT-B TOI score

    Measured: Baseline, up to approximately 38 months

  10. Part 2: PFS based on local radiology assessments by PIK3CA mutation status

    Evaluate the association between PIK3CA mutation status as measured in ctDNA at baseline with PFS upon treatment with alpelisib. PFS will be assessed using RECIST 1.1 criteria for patients by PIK3CA mutation status assessed in ctDNA at baseline.

    Measured: Up to approximately 38 months

  11. Part 2: Time to definitive deterioration of Eastern Cooperative Group of Oncology Group (ECOG) performance status

    ECOG: participant's performance status was measured on a 6-point scale: 0= fully active/able to carry on all pre-disease activities without restriction; 1= restricted in physically strenuous activity but ambulatory and able to carry out work of a light and sedentary nature; 2= ambulatory and capable of all self-care, but unable to carry out any work activities, up and about more than 50 percent (%) of waking hours; 3= capable of only limited self-care, confined to bed/chair >50% of waking hours; 4= completely disabled, cannot carry on any self-care, totally confined to bed/chair: 5= dead. Time to definitive deterioration in ECOG PS is defined as the time from the date of randomization to the date when the ECOG PS has definitely deteriorated by at least one category compared with baseline. Deterioration is considered definitive if there is no subsequent improvement in ECOG PS back to baseline category or above.

    Measured: Baseline, up to approximately 38 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Dec 2019
  2. Study start16 Jul 2020
  3. Primary completion26 Feb 2027 (estimated)
  4. Study completion26 Feb 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Sequential
Model description
Part 1 was the open-label, safety run-in part of the study designed to confirm the recommended phase 3 dose (RP3D) dose of alpelisib in combination with trastuzumab and pertuzumab. Following Part 1, Part 2 was initiated, which is the randomized, Phase III part of the study with two treatment arms.
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
19 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04208178
Sponsor's protocol ID
CBYL719G12301
Other IDs
2024-512050-13-00
Acronym
EPIK-B2
Status last verified
Sep 2026
First submitted
12 Dec 2019
Last updated
18 Sep 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: 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 expert 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 is currently available according to the process described on www.clinicalstudydatarequest.com.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Alpelisib, Trastuzumab and Pertuzumab in people with Advanced HER2+Breast Cancer, run by Novartis Pharmaceuticals at 11 sites in 7 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 18 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 11 sites in United States, Belgium, China, France, Italy and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Part 1: Incidence of dose limiting toxicities (DLTs) for each dose level (time frame: 6 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04208178.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Sep 2026.

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