Abstract 200TiP
Background
PIK3CA mutations can be found in about 20%-30% of HER2+ BC pts and indicate a lower response to chemotherapy and anti-HER2 therapy, especially in HER2+/HR+ tumours (Loibl S 2014 and 2016). Crosstalk exists between key signalling pathways (ER, HER2 and PI3K) and inhibition of PI3K results in the activation of HER2-pathway (Serra V 2011). The phase III Solar-1 study demonstrated a significant improvement in progression free survival with the addition of alpelisib to fulvestrant in PIK3CA mutant metastatic BC (André F 2019). GeparPiPPa investigates in the neoadjuvant setting the efficacy and safety of inavolisib, an oral pure PI3Kα inhibitor, in addition to endocrine and anti-HER2 therapy in pts with early HER2+/HR+ and PIK3CA mutant BC.
Trial design
GeparPiPPa (NCT 05306041) is a multicentre, open-label, phase II study. Pts are eligible with cT1c – cT3 disease, centrally confirmed HER2+ and HR+-status as well as a PIK3CA tumour mutation (by NGS). A good performance status (ECOG PS 0-1) and adequate organ functions are required. Pts with a body mass index >30, diabetes mellitus type I or uncontrolled type II, and/or a history of BC within the last 5 years are excluded. Primary endpoint is pathological complete response (pCR; ypT0/is ypN0). Secondary endpoints include comparison of other pCR definitions, breast conservation rate, invasive disease-free survival, overall survival, safety, and tolerability. Approximately 170 pts will be randomised in a 1:1 ratio to receive 6 cycles (18 weeks) of tamoxifen or an aromatase inhibitor (1x1/d orally, day 1-21 q3w) +/- gonadotropin-releasing hormone analogue plus pertuzumab/trastuzumab (subcutaneous formulation [1200 (600) mg/600 mg on d1, q3w]) without or with inavolisib (9mg 1x1/d orally, day 1-21 q3w). Stratification will be by nodal status (cN0 vs cN+) and study group (GBG vs IBCSG). After end of therapy, pts will undergo a core biopsy and/or definitive surgery. Further (neo)adjuvant systemic treatment and radiotherapy will be administered at the discretion of the investigator according to standard of care.
Clinical trial identification
EudraCT 2021-002323-38 NCT 05306041.
Editorial acknowledgement
Legal entity responsible for the study
GBG Forschungs GmbH.
Funding
Roche.
Disclosure
S. Loibl: Financial Interests, Institutional, Research Grant, honorarium for Ad Boards, paid to institute: AbbVie, Celgene; Financial Interests, Institutional, Other, honorarium for Ad Boards, paid to institute: Amgen, BMS, Eirgenix, GSK, Lilly, Merck; Financial Interests, Institutional, Research Grant, honorarium for Ad Boards & Lectures, paid to institute: AstraZeneca; Non-Financial Interests, Institutional, Research Grant, honorarium for Ad Board, paid to institute / Medical Writing: Gilead, Novartis, Pfizer, Daiichi Sankyo, Roche; Financial Interests, Institutional, Other, honorarium for Ad Board & Lecture, paid to institute: Pierre Fabre; Non-Financial Interests, Institutional, Other, honorarium for Ad Board, paid to institute / Medical Writing: Seagen; Financial Interests, Institutional, Other, honorarium for Ad Board, paid to institute: Sanofi; Financial Interests, Institutional, Other, Patent for Immunsignature in TNBC, paid to institute: EP14153692.0; Financial Interests, Institutional, Other, Patent for Signature for CDK 4/6 Inhibitor, paid to institute: EP21152186.9; Financial Interests, Institutional, Other, Paten for Predicting response to an Anti-HER2 containing therapy, paid to institute: EP15702464.7; Financial Interests, Institutional, Other, Paten for GeparNuevo, paid to institute: EP19808852.8; Financial Interests, Institutional, Royalties, VM Scope GmbH, paid to institute: Digital Ki67 Evaluator. M. Reinisch: Financial Interests, Personal, Other: AstraZeneca, Daiichi Sankyo, MSD, Roche, Pfizer, Seagen; Non-Financial Interests, Personal, Other, Travel expenses: Novartis; Non-Financial Interests, Personal, Other, Travel Support: Lilly. C. Denkert: Other, Institutional, Research Grant: Myriad, Roche; Financial Interests, Personal and Institutional, Royalties: VmScope digital pathology software; Financial Interests, Personal and Institutional, Advisory Role: MSD Oncology, Daiichi Sankyo, Molecular Health, Merck, Lilly; Financial Interests, Personal and Institutional, Advisory Role, Payment or honoraria for lectures: AstraZeneca; Financial Interests, Personal and Institutional, Advisory Role, Support for attending meetings and/or travel: Roche; Financial Interests, Personal and Institutional, Other, Patents for therapy response: WO2015114146A1 and WO2010076322A1; Financial Interests, Personal and Institutional, Other, Patent for cancer immunotherapy: WO2020109570A1; Financial Interests, Personal, Ownership Interest, cofounder and shareholder until 2016: Sividon Diagnostics. P.A. Fasching: Financial Interests, Personal, Advisory Board: Roche, Novartis, Pfizer, Daiichi Sankyo, Eisai, Merck, Sharp & Dohme, Astrazeneca, Hecal, Lilly, Pierre Fabre, Seagen, Agendia; Financial Interests, Personal, Invited Speaker: Novartis, Daiichi Sankyo, Eisai, Merck, Sharp & Dohme, AstraZeneca, Lilly, Seagen; Financial Interests, Personal, Other, Medical Writing Support: Roche; Financial Interests, Institutional, Invited Speaker: BionTech, Cepheid; Non-Financial Interests, Member: ASCO, Arbeitsgemeinschaft für Gynäkologische Onkologie e.V., Translational Research in Oncology, Deutsche Gesellschaft für Senologie e.v. S. Seiler: Financial Interests, Institutional, Research Grant: Roche; Financial Interests, Personal, Other, Presentations: AbbVie. T. Link: Financial Interests, Personal, Other: Amgen, Roche, Novartis, Lilly, GSK, Tesaro, Myriad, Esai; Non-Financial Interests, Personal, Other: Gilead, Daiichi Sankyo, MSD, Clovis, Pfizer; Non-Financial Interests, Other: Celgene. C. Hanusch: Financial Interests, Personal, Other: Roche, Novartis, AstraZeneca. A. Schneeweiss: Other, Institutional, Research Grant: BMS (Celgene), Roche, AbbVie; Financial Interests, Personal, Other, Travel expenses, Honoraria: BMS (Celgene), Roche; Financial Interests, Personal, Other, Honoraria, Travel expenses: Pfizer; Financial Interests, Personal, Other, Honoraria: AstraZeneca, Novartis, MSD, Tesaro, Lilly, Seagen, Gilead, GSK, Bayer, Amgen, Pierre Fabre. J. Huober: Financial Interests, Personal and Institutional, Research Grant: Lilly, Novartis, Celgene; Financial Interests, Personal, Other, Travel expenses: Roche, Pfizer; Financial Interests, Personal, Other: Gilead, Daiichi, AstraZeneca, Seagen, MSD, AbbVie; Financial Interests, Institutional, Research Grant: Hexal. C. Jackisch: Financial Interests, Personal, Other: Roche, AstraZeneca, Lilly, Novartis. M. Untch: Non-Financial Interests, Personal and Institutional, Other, All fees to the institution/employer: Amgen GmbH; Non-Financial Interests, Personal and Institutional, Other: AstraZeneca, Celgene GmbH, Daiichi Sankyo, Eisai, Lilly Int., MSD Merck, Myriad Genetics, Pfizer GmbH, Roche Pharma AG, Sanofi Aventis Deutschland GmbH, Novartis, Clovis Oncology, Seatlle Genetics, Seagen, GSK, Gilead; Financial Interests, Personal and Institutional, Other: Lilly Deutschland, Pierre Fabre. S. Loi: Financial Interests, Institutional, Research Grant, Research funding to institution, Consulting (paid to institution): Novartis; Non-Financial Interests, Other, Consulting (Non compensated): Seattle Genetics, Novartis, Bristol Meyers Squibb, Merck, AstraZeneca, Eli Lilly, Pfizer, Gilead Therapeutics and Roche-Genentech; Financial Interests, Institutional, Other, Consulting (Non compensated): Aduro Biotech, GlaxoSmithKline, Silverback Therapeutics, G1 Therapeutics, Gilead Therapeutics, Amunix, Tallac Therapeutics; Financial Interests, Institutional, Research Grant, Consulting (paid to institution): Bristol Meyers Squibb, Merck, Puma Biotechnology, Eli Lilly, AstraZeneca, Roche-Genentech, Seattle Genetics; Financial Interests, Institutional, Research Grant: Nektar Therapeutics; Financial Interests, Institutional, Other, Consulting (paid to institution): Pfizer, Daiichi Sankyo. All other authors have declared no conflicts of interest.