Maintenance Therapy Study of Inavolisib with Pertuzumab and Trastuzumab in Patients with HER2‑Positive, PIK3CA‑Mutated Locally Advanced or Metastatic Breast Cancer

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What is this study about?

A clinical study is focused on people with HER2‑positive, PIK3CA‑mutated, locally advanced or metastatic breast cancer, a type of breast cancer that has spread beyond the breast and carries specific genetic changes. The investigational medicine being tested is a pill called Inavolisib, which is taken by mouth, and it is given together with an injected combination product called Phesgo that contains the antibodies trastuzumab and pertuzumab. These drugs work by targeting the HER2 protein on cancer cells and by blocking a growth pathway that is activated by the PIK3CA mutation. The study also includes a group that receives a matching pill without the active drug (placebo) together with the same injection, allowing a comparison of the two approaches.

The purpose of the study is to find out whether adding Inavolisib to the standard injection improves the time that cancer does not get worse, known as progression‑free survival. Participants who have already completed an initial course of treatment are randomly assigned, without knowing which group they are in, to continue receiving either the new pill plus the injection or the placebo pill plus the injection. Treatment is given regularly over several months, and doctors will monitor the participants with routine health checks, scans, and blood tests to see how the cancer behaves and to record any side effects. The study also looks at overall survival, how well the tumor responds, and quality of life during the treatment period.

1 baseline assessment and randomization

after joining the study you will undergo baseline blood tests, imaging scans and other evaluations to confirm eligibility.

based on these results you will be randomly assigned to receive either inavolisib plus phesgo or a matching placebo plus phesgo.

2 subcutaneous injection of phesgo

each treatment cycle you will receive a subcutaneous injection (under the skin) of phesgo, which contains trastuzumab and pertuzumab combined for a total dose of 1800 mg.

the injection is given according to the study schedule, typically every three weeks, and is administered by healthcare staff.

3 daily oral tablet of inavolisib or placebo

you will take one film‑coated tablet containing 9 mg of inavolisib each day.

if you are assigned to the placebo group, you will take an identical tablet that does not contain the active drug.

the tablet is taken orally with water, at the same time each day, throughout the maintenance phase.

4 background oral therapies (if applicable)

depending on hormone‑receptor status, you may continue oral hormonal medicines such as:

tamoxifen 20 mg taken once daily
anastrozole 1 mg taken once daily
letrozole 2.5 mg taken once daily
exemestane 25 mg taken once daily

these medications are taken by mouth each day for the duration of the study.

5 regular clinic visits for monitoring

you will attend clinic visits at intervals defined by the protocol, generally every three weeks, for safety checks.

at each visit blood samples will be drawn, and periodic imaging scans will be performed to assess disease status.

6 management of side effects

if you experience side effects, you will report them to the study team.

the team may pause treatment, adjust the dose of inavolisib, or provide supportive medication according to predefined guidelines.

7 continuation until progression or study end

you will continue the combination of subcutaneous phesgo and daily oral inavolisib (or placebo) until one of the following occurs:

radiographic or clinical disease progression
unacceptable toxicity that cannot be managed
the planned end of the study period (estimated 2028‑12‑31)

8 final assessment and study exit

when treatment stops, you will undergo a final set of assessments, including blood tests and imaging, to document the outcome of the study.

after the final assessment you will be discharged from the trial and may return to standard follow‑up care.

Who Can Join the Study?

Be at least 18 years old when signing the consent form.
Have breast cancer that has been confirmed by a laboratory examination of tumor tissue, specifically an adenocarcinoma that is locally advanced or has spread and cannot be cured by surgery.
Show HER2‑positive status, meaning a lab test on the tumor tissue found high levels of the HER2 protein that can help cancer grow.
Show a PIK3CA mutation in the tumor, meaning a specific genetic change in the cancer cells identified by a lab test.
Have a gap of at least 6 months between finishing previous non‑hormonal chemotherapy (adjuvant or neoadjuvant treatment) and the return of the cancer.
Have an ECOG Performance Status of 0 or 1, which means you are fully active (0) or able to do light work but not physically strenuous activity (1).
Have a heart pumping measurement called LVEF of at least 50%, measured by an echocardiogram (ultrasound of the heart) or a MUGA scan (special imaging test).
Have adequate blood counts and organ health (kidney, liver, etc.) before starting the study treatment, referred to as adequate hematologic and organ function.
Complete 4‑8 cycles of induction therapy, which is the initial treatment given before the maintenance part of the study.
After those cycles, show either a partial response (cancer has shrunk), a complete response (cancer is no longer detectable), or stable disease (cancer has not grown), according to RECIST v1.1 criteria.

Who Cannot Join the Study?

Any previous use of a systemic non‑hormonal anti‑cancer therapy (medicine that treats the whole body and is not a hormone) for advanced HER2‑positive breast cancer before starting the initial treatment.
Having a serious infection that required intravenous (IV) antibiotics (medicine given through a vein) within 7 days before the first day of the study.
Having any current eye condition (both outside and inside the eye, called ocular or intraocular) that the doctor believes would need medical or surgical treatment during the study to prevent vision loss.
Having active inflammation or infection in either eye, or a past history of unknown‑cause (idiopathic) or immune‑related eye inflammation known as uveitis.
Having symptomatic active lung disease, including lung inflammation called pneumonitis or scarring/patchy damage called interstitial lung disease.
Having a history of or current inflammatory bowel disease (such as Crohn’s disease or ulcerative colitis) or ongoing chronic diarrhea.
Having clinically significant and active liver disease, such as severe liver impairment, viral hepatitis (liver infection), current alcohol abuse, or cirrhosis (scarring of the liver).
Having previously been treated in the advanced disease setting with any drug that blocks the PI3K, AKT, or mTOR pathway (these are signals that help cancer cells grow).
Being pregnant, breastfeeding, planning to become pregnant during the study, or planning to become pregnant within 7 months after the last dose of Phesgo.
Having Type 2 diabetes that requires ongoing medication at the time of study entry, or any history of Type 1 diabetes.
Any history of leptomeningeal disease (cancer spread to the membranes covering the brain and spinal cord) or carcinomatous meningitis (cancer cells in those membranes).

Where you can join this trial?

Verified and Recommended Sites

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Verified Sites

Site Name	City	Country	Status
Centr Georges Francois Leclerc	Dijon	France
Szpital Wojewodzki Im. Mikolaja Kopernika W Koszalinie	Koszalin	Poland

Other Sites

Site Name	City	Country
Institut Jules Bordet	Anderlecht	Belgium
Ospedale San Raffaele S.r.l.	Milan	Italy
Centre Hospitalier De La Cote Basque	Bayonne	France
Azienda Ospedaliero-Universitaria Maggiore Della Carita	Novara	Italy
Istituto Europeo Di Oncologia S.r.l.	Milan	Italy
Centre hospitalier universitaire de Liege	Liege	Belgium
Algemeen Ziekenhuis Klina	Brasschaat	Belgium
Centre Hospitalier Regional De La Citadelle	Liege	Belgium
AZ Sint-Lucas & Volkskliniek	Gent	Belgium
CHR Verviers	Verviers	Belgium
Chirec	Brussels	Belgium
Grand Hopital De Charleroi	Charleroi	Belgium
Marienhospital Bottrop gGmbH	Bottrop	Germany
HELIOS Klinikum Berlin-Buch GmbH	Berlin	Germany
Caritas Traegergesellschaft Saarbruecken mbH (CTS)	Saarbrücken	Germany
Universitaetsklinikum Erlangen AöR	Erlangen	Germany
Tampere University Hospital	Tampere	Finland
Universita’ Degli Studi Di Verona	Verona	Italy
Narodowy Instytut Onkologii Im. Marii Sklodowskiej-Curie-Panstwowy Instytut Badawczy	Warsaw	Poland
Turku University Hospital	Turku	Finland
Ludwig Maximilian University Of Munich	Munich	Germany
Jessa Ziekenhuis	Hasselt	Belgium
Polyclinique Bordeaux Nord Aquitaine	Bordeaux	France
CHU Helora	La Louviere	Belgium
Centrum Onkologii Im. Prof. Franciszka Lukaszczyka W Bydgoszczy	Bydgoszcz	Poland
Institut fuer Klinische Transfusionsmedizin und Immungenetik Ulm gGmbH	Ulm	Germany
Hospital General Universitario Gregorio Maranon	Madrid	Spain
Hospital Universitario 12 De Octubre	Madrid	Spain
Vrije Universiteit Brussel	Jette	Belgium
Hospital Universitari Dexeus Grupo Quironsalud	Barcelona	Spain
Wielkopolskie Centrum Onkologii Im. Marii Sklodowskiej-Curie	Poznan	Poland
Centre Hospitalier Universitaire Dinant Godinne Sainte-Elisabeth-UCL-Namur	Namur	Belgium
Klinikum St Marien Amberg	Amberg	Germany
Institut Sainte Catherine	Avignon	France
Fondazione IRCCS San Gerardo Dei Tintori	Monza	Italy
Vaasa Central Hospital	Vaasa	Finland
Praxis Fuer Interdisziplinaere Onkologie And Haematologie GbR	Freiburg Im Breisgau	Germany
Fondazione I.R.C.C.S. Istituto Neurologico Besta	Milan	Italy
Institut fuer Diabetesforschung Muenster GmbH	Munster	Germany
Hospital Universitario Virgen De La Victoria	Malaga	Spain
Association Hospitaliere De Bruxelles Et De Schaerbeek Centre Hospitalier Universitaire Brugmann	Brussels	Belgium
I Przychodnia Lekarska Komed Roman Karaszewski II Osrodek Badan Klinicznych III Restauracja Rogatka Roman Karaszewski	Konin	Poland
Azienda USL Toscana Centro	Bagno A Ripoli	Italy
Ixymxfhb Rmushyuir Pcx Ln Sdkkuy Dhj Txsewf Dfaw Aijdxiq Ijbq Sgmofj	Meldola	Italy
Dyq Aeyi Mgsxxbckjmyf Veszschyon Gjrl	Erfurt	Germany
Lf Mtgjtxyip Sauhlk	Palermo	Italy
Cpcfonnzi Uhchivpzdxditt Sosxobxas	Woluwe-Saint-Lambert	Belgium
Usmzokcmrzqkxd Cxwjsnx Kklarupmr	Gdansk	Poland
Awdixbc Oyuaotkxlpv S Gvjxqmxk Aetbactixr	Rome	Italy
Ssvnjbao Pbphsvbgc Spe z opvy	Gdynia	Poland
Muc Mnaqccn Cqeock Druvptriewz Gqgj	Duesseldorf	Germany
Hagwyikb Vrus djdjsggn	Barcelona	Spain
Cffnii Ogwlg Lbmattf	Lille	France
Hpovaaop Uojywqusfoxkc dy A Crkqbr	A Coruna Galicia	Spain

Trial status

Country	Status	Recruitment Start
Belgium	Recruiting	31.07.2023
Finland	Not recruiting	31.07.2023
France	Recruiting	31.07.2023
Germany	Recruiting	31.07.2023
Italy	Recruiting	31.07.2023
Poland	Recruiting	31.07.2023
Spain	Recruiting	31.07.2023

Trial locations

Investigated drugs:

Inavolisib
Inavolisib is an oral medication taken as a tablet. In this study it is the experimental drug being tested to see if it can help keep breast cancer from growing after the initial treatment. Participants receive Inavolisib together with the injection therapy to see if it improves the time before the cancer gets worse.

Phesgo
Phesgo is a specially formulated injection that contains two antibodies, trastuzumab and pertuzumab, which target the HER2 protein on cancer cells. It is given under the skin and is used in this trial as a maintenance therapy after the first‑line treatment. The study compares Phesgo combined with Inavolisib to Phesgo combined with a placebo to see which works better at controlling the disease.

Tamoxifen
Tamoxifen is an oral hormone‑blocking medicine that is often used in breast cancer. In this trial it is part of the background (standard) therapy that participants may have received before starting the maintenance phase. It helps prevent estrogen from stimulating any remaining cancer cells.

Anastrozole
Anastrozole is a pill taken by mouth that reduces the amount of estrogen made by the body. It is included as one of the standard background treatments for participants who have hormone‑sensitive breast cancer, helping to keep cancer growth in check.

Letrozole
Letrozole is another oral medication that lowers estrogen levels. Like the other hormone therapies, it is part of the background treatment given before the maintenance period, aiming to limit estrogen‑driven tumor growth.

Exemestane
Exemestane is an oral drug that blocks estrogen production. It is used as a standard background therapy for participants, helping to reduce the hormone support that some breast cancers need to grow.

Paclitaxel albumin‑bound
Paclitaxel albumin‑bound is a chemotherapy drug given through an IV. It is part of the standard treatment given during the first‑line phase of therapy before participants move on to the maintenance part of the study.

Paclitaxel
Paclitaxel is an IV chemotherapy medication used as part of the background (initial) treatment regimen. It works by stopping cancer cells from dividing and is given before the maintenance therapy begins.

Anhydrous docetaxel
Anhydrous docetaxel is an IV chemotherapy drug used in the initial treatment of breast cancer. It helps kill cancer cells by interfering with their growth cycle and is part of the standard therapy before the maintenance phase.

Goserelin acetate
Goserelin acetate is an injectable hormone therapy that lowers the production of certain hormones that can fuel breast cancer growth. It is given as part of the background treatment plan before participants start the maintenance therapy being studied.

Investigated diseases:

HER2-Positive, PIK3CA Mutated, Locally Advanced or Metastatic Breast Cancer – This disease is a form of breast cancer in which tumor cells have excess HER2 protein and a mutation in the PIK3CA gene. It is classified as locally advanced when it has grown beyond the breast but not yet spread widely, and metastatic when it has spread to other organs. The HER2 overexpression drives rapid cell growth, while the PIK3CA mutation further enhances tumor proliferation. Over time the cancer may involve nearby lymph nodes and distant sites such as bone, liver, or lungs. Progression is monitored by increasing tumor size or the appearance of new metastatic lesions.

Trial ID:

2022-502046-28-00

Protocol code:

WO44263

Trial Phase:

Therapeutic confirmatory (Phase III)

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Maintenance Therapy Study of Inavolisib with Pertuzumab and Trastuzumab in Patients with HER2‑Positive, PIK3CA‑Mutated Locally Advanced or Metastatic Breast Cancer

What is this study about?

Who Can Join the Study?

Who Cannot Join the Study?