This is a multicenter, prospective, randomized, open-label, parallel-group, phase II study to evaluate the potential incremental efficacy and safety of
inavolisib in the neoadjuvant treatment of early-stage HER2-positive, HR-positive, PIK3CA mutant breast cancer.
170 patients with confirmed eligibility criteria and PIK3CA mutant breast cancer will be randomized in a 1:1 ratio to receive: 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) • with inavolisib (6 cycles) or • without inavolisib. Endocrine therapy consists of either tamoxifen 20mg or an aromatase inhibitor +/- GnRH analogue. In both study arms, treatment will be given until surgery/core-biopsy, disease progression, unacceptable toxicity, or withdrawal of consent of the patient. All patients will undergo surgery or biopsy after completing study therapy to
assess pCR rate. In case of ycT0 and no tumor residuals in the biopsy, it is recommended to undergo surgery; in case of tumor residuals in the biopsy
further neoadjuvant treatment may be given (the patient will be considered no pCR for the study regardless of the response to the further neoadjuvant
treatment). Pseudonymized histology and surgery reports will be collected. Further neoadjuvant or adjuvant treatment including chemotherapy, radiotherapy, endocrine therapy and HER2-therapy will be administered at the discretion of the investigator and according to standard of care. Information on those additional adjuvant treatments will be captured within a registry.
The study investigates the potential efficacy and safety of inavolisib in the neoadjuvant treatment of HER2-positive, HR-positive, PIK3CA-mutated breast cancer.
170 patients with confirmed inclusion criteria and PIK3CA-mutated breast cancer will receive neoadjuvant endocrine therapy in combination with dual anti-HER2 blockade consisting of a ready-to-use fixed-dose combination of pertuzumab and trastuzumab as a subcutaneous (PH-FDC SC) formulation q3w for 6 cycles (18 weeks), randomized 1:1 with or without inavolisib.
Endocrine therapy consists of either tamoxifen 20mg or an aromatase inhibitor +/- GnRH analogue for premenopausal women and men.
To assess the pCR rate, all patients will undergo surgery or biopsy after completion of study therapy. In case of ypT0 and no residual tumor in the biopsy, surgery is recommended; if residual tumor in the biopsy is present, further neoadjuvant treatment may be performed.
