Neoadjuvant Endocrine Therapy +/- the PI3K Inhibitor Inavolisib in HER2+, HR+, PIK3CA Mutant Early Breast Cancer

NCT05306041 | Recruiting Phase 2 DMC

• 1 other identifier: GBG105
• Study Type: interventional
• Target: 170
• Locations: 2 countries
• Sites: 29

Brief Summary

Evaluation of the potential incremental efficacy and safety of inavolisib in the neoadjuvant endocrine treatment of early-stage HER2-positive, HR-positive, PIK3CA mutant breast cancer.

Conditions

HER2-positive Breast Cancer

Keywords

GeparPiPPa; German Breast Group

Outcome Measures

Primary Outcomes (1)

• Pathologic complete response in the breast and axillary lymph nodes (ypT0/is ypN0)

  Pathological complete response (ypT0/is ypN0) is defined as no microscopic evidence of residual invasive tumor cells in all resected specimens of the breast and axilla.

  21 weeks (time window + 3 weeks)

Secondary Outcomes (8)

• Rates of ypT0 ypN0; ypT0 ypN0/+; ypT0/is ypN0/+; ypT(any) ypN0

  21 weeks (time window + 3 weeks)

• pCR rates per arm separately for the stratified subpopulations

  21 weeks (time window + 3 weeks)

• Response rates of the breast tumor and axillary nodes based on physical examination and imaging tests (sonography, mammography, or MRI) after study treatment in both arms

  21 weeks (time window + 3 weeks)

• Percentage of patients receiving additional neoadjuvant chemotherapy after residual disease was confirmed by core biopsy at the end of study treatment

  21 weeks (time window + 3 weeks)

• Breast conservation rate after treatment

  21 weeks (time window + 3 weeks)

Study Arms (2)

Inavolisib

EXPERIMENTAL

Inavolisib for 6 cycles (18 weeks) Neoadjuvant endocrine therapy in combination with dual anti-HER2 blockade consisting of ready-to-use fixed-dose combination of pertuzumab and trastuzumab as subcutaneous (PH-FDC SC) formulation q3w for 6 cycles (18 weeks)

Drug: Inavolisib; Drug: PHESGO; Drug: Endocrine therapy

without Inavolisib

OTHER

Neoadjuvant endocrine therapy in combination with dual anti-HER2 blockade consisting of ready-to-use fixed-dose combination of pertuzumab and trastuzumab as subcutaneous (PH-FDC SC) formulation q3w for 6 cycles (18 weeks)

Drug: PHESGO; Drug: Endocrine therapy

Interventions

Inavolisib DRUG

daily application of 9 mg (may be decreased to 6 mg and to 3 mg)

Inavolisib

PHESGO DRUG

fixed-dose combination of pertuzumab and trastuzumab with hyaluronidase s.c. (PH-FDC SC) q3w beginning on day 1 of cycle 1 for 6 cycles (18 weeks)

Inavolisib; without Inavolisib

Endocrine therapy DRUG

Endocrine therapy per physician´s choice with either tamoxifen 20mg or an aromatase inhibitor +/- GnRH analogue for premenopausal women and men

Inavolisib; without Inavolisib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent for all study procedures according to local regulatory requirements prior to beginning specific protocol procedures.
• Untreated, unilateral primary carcinoma of the breast, confirmed histologically by core biopsy. Fine-needle aspiration alone is not sufficient. Incisional biopsy is not allowed.
• Tumor lesion in the breast must be measurable in two dimensions, preferably by sonography.
• Patients must be in the following stages of disease:
• cT1b - cT3 regardless of nodal status In patients with multifocal or multicentric breast cancer the largest lesion (target lesion) should be measured.
• HR+/HER2+ disease with centrally confirmed ER-status, PR-status, HER2-status, PIK3CA mutation (tumor), Ki-67 value and TILs on core biopsy (target lesion). ER/PgR positive and HER2-positive is defined according to current ASCO/CAP guidelines. Formalin-fixed, paraffin-embedded (FFPE) breast tissue from core biopsy of target lesion has therefore to be sent to the GBG central pathology laboratory prior to randomization. In patients with multifocal or multicentric breast cancer, all non-target lesions must also be HR+/HER2+, as confirmed by local testing.
• Age ≥ 18 years, female and male.
• ECOG Performance status 0-1.
• Normal cardiac function must be confirmed by ECG and cardiac ultrasound (LVEF or shortening fraction) within 3 months prior to randomization. Results for LVEF must be above 55%.
• Laboratory requirements:
• Hematology
• Absolute neutrophil count (ANC) ≥ 1.5/ nL
• Platelets ≥ 100/ nL and
• Hemoglobin ≥ 10 g/dL (≥ 6.2 mmol/L) Hepatic function
• Total bilirubin \< ULN except for patients with Gilbert's syndrome who may only be included if the total bilirubin is ≤ 3.0 × ULN or direct bilirubin ≤ 1.5 × ULN

You may not qualify if:

• Patients with HER2-negative breast cancer and/or HER2-positive, HR-negative breast cancer.
• Need of immediate neoadjuvant chemotherapy, e.g. inflammatory breast cancer.
• Patients with definitive clinical or radiologic evidence of Stage IV cancer.
• Excisional biopsy or lumpectomy and /or axillary lymph node dissection and/or sentinel lymph node biopsy performed prior to study entry (biopsy of clinical involved LN is warranted).
• Prior chemotherapy or endocrine therapy or radiation therapy prior to study entry with the following exceptions:
• If medically indicated, initiation of endocrine therapy up to 28 days prior to randomization and use of established fertility preservation methods in young patients interested in subsequent pregnancies is allowed.
• Patients with a history of breast cancer are ineligible with the following exceptions:
• Patient has been disease-free for more than 5 years and is at low risk for recurrence (at the investigator's discretion).
• Patients with a history of any treated malignancy are ineligible in case of high risk of recurrence (at the investigator's discretion) and/or ongoing oncological treatment. This also applies to patients who are at high risk that oncological treatment is indicated during study therapy.
• Patients with BMI\>30 can be included at the investigator's discretion.
• Known hypersensitivity reaction to one of the compounds or substances, and/or murine proteins, and/or recombinant human hyaluronidase used in this protocol.
• Patients with an established diagnosis of diabetes mellitus type I or uncontrolled type II based on FPG and HbA1c.
• Patients who are immunocompromised as the result of HIV or receiving immunosuppressive therapies.
• Clinically significant and active liver disease, for example, sclerosing cholangitis, active viral hepatitis B or C infection, or autoimmune hepatic disorders.
• Patients with inflammatory bowel disease, such as Crohn's disease or ulcerative colitis, and active bowel inflammation (e.g., diverticulitis).

Sponsors & Collaborators

• GBG Forschungs GmbH: lead
• Roche Pharma AG: collaborator

Study Sites (29)

KEM Kliniken Essen-Mitte

Essen, North Rhine-Westphalia, 45136, Germany

RECRUITING

Hämatologie-Onkologie im Zentrum MVZ GmbH

Augsburg, 86150, Germany

RECRUITING

DBZ Onkologie

Berlin, 12623, Germany

NOT YET RECRUITING

Praxisklinik Krebsheilkunde für Frauen

Berlin, 13597, Germany

RECRUITING

Onkologische Schwerpunktpraxis Bielefeld

Bielefeld, 33604, Germany

RECRUITING

Department of Breast-Center Holweide - Kliniken der Stadt Köln

Cologne, 51067, Germany

RECRUITING

Städtisches Klinikum Dessau

Dessau, 06847, Germany

NOT YET RECRUITING

University Hospital Carl Gustav Carus

Dresden, 01307, Germany

RECRUITING

Center for Gynecologic Oncology

Düsseldorf, 40235, Germany

RECRUITING

Frauenklinik des Universitätsklinikums Erlangen

Erlangen, 91054, Germany

NOT YET RECRUITING

Klinik für Gynäkologie und Geburtshilfe Agaplesion Markus Krankenhaus

Frankfurt, 60431, Germany

RECRUITING

SRH Wald-Klinikum Gera GmbH

Gera, 07548, Germany

RECRUITING

Mammazentrum HH am Krankenhaus Jerusalem

Hamburg, 20357, Germany

RECRUITING

Klinikum Hanau

Hanau, 63450, Germany

NOT YET RECRUITING

DIAKOVERE Henriettenstift Frauenklinik

Hanover, 30171, Germany

NOT YET RECRUITING

National Center for Tumor Diseases - University Hospital Heidelberg

Heidelberg, 69120, Germany

RECRUITING

Elisabeth Krankenhaus Brustzentrum

Kassel, 34117, Germany

RECRUITING

Praxis für Hämatologie und Onkologie Koblenz and InVo - Institut für Versorgungsforschung in der Onkologie GbR

Koblenz, 56068, Germany

RECRUITING

University Hospital Mannheim

Mannheim, 68167, Germany

NOT YET RECRUITING

University Hospital Gießen and Marburg, Campus Marburg

Marburg, 35043, Germany

NOT YET RECRUITING

Media Vita GmbH (MVZ)

Münster, 48145, Germany

NOT YET RECRUITING

University Hospital Tübingen

Tübingen, 72076, Germany

RECRUITING

Department of Gynecology and Obstetrics - University of Ulm

Ulm, 89075, Germany

NOT YET RECRUITING

GRN Klinik Weinheim

Weinheim, 69469, Germany

NOT YET RECRUITING

Klinikum Worms

Worms, 67550, Germany

NOT YET RECRUITING

Helios Universitätsklinikum Wuppertal

Wuppertal, 42283, Germany

RECRUITING

Università Politecnica delle Marche - Azienda Ospedaliero Universitarià delle Marche

Ancona, Italy

NOT YET RECRUITING

AULSS9 Scaligera - Ospedale Mater Salutis di Legnago

Legnago, 37045, Italy

NOT YET RECRUITING

Istituto Europeo di Oncologica

Milan, 20141, Italy

RECRUITING

MeSH Terms

Interventions

inavolisib

Study Officials

• Mattea Reinisch, PD Dr. med.

  Universitätsmedizin Mannheim, Frauenklinik mit Brustzentrum

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jana Roßney

CONTACT

+49(0)6102 7480; geparpippa@gbg.de

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 9, 2022
• First Posted: March 31, 2022
• Study Start: January 2, 2023
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): January 1, 2027
• Last Updated: February 17, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

DE (26); IT (3)