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.
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.
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.
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).
Parallel
Inavolisib
Drugdaily application of 9 mg (may be decreased to 6 mg and to 3 mg)
PHESGO
Drugfixed-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)
Endocrine therapy
DrugEndocrine therapy per physician´s choice with either tamoxifen 20mg or an aromatase inhibitor +/- GnRH analogue for premenopausal women and men
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.
Rates of ypT0 ypN0; ypT0 ypN0/+; ypT0/is ypN0/+; ypT(any) ypN0
ypT0 ypN0 is defined as no microscopic evidence of residual invasive or non-invasive viable tumor cells in all resected specimens of the breast and axilla; ypT0 ypN0/+ is defined as no microscopic evidence of residual invasive or non-invasive viable tumor cells in all resected specimens of the breast; ypT0/Tis ypN0/+ is defined as no microscopic evidence of residual invasive viable tumor cells in all resected specimens of the breast
pCR rates per arm separately for the stratified subpopulations
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.
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
Clinical (c) and imaging (i) response will be assessed every 2nd cycle and before surgery by physical examination and imaging tests. Sonography is the preferred examination. The response categories of the breast are: * Complete response (CR): complete disappearance of all tumor signs in the breast * Partial response (PR): reduction in the product of the two largest perpendicular diameters of the primary tumor size by 50% or more * Stable disease (NC): no significant change in tumor size during treatment which means an estimated reduction of the tumor area by less than 50%, or an estimated increase in the size of the tumor area lesions of less than 25% * Progressive disease (PD): development of new, previously undetected lesions, or an estimated increase in the size of pre-existing lesions by 25% or more after at least two cycles of therapy
Percentage of patients receiving additional neoadjuvant chemotherapy after residual disease was confirmed by core biopsy at the end of study treatment
In case of ycT0 and no tumor residuals in the biopsy, it is recommended to undergo surgery. 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.
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GBG Forschungs GmbH
Lead sponsor
Roche Pharma AG
Collaborator
