Phase II Study of Neoadjuvant Endocrine Therapy With or Without the PI3K Inhibitor Inavolisib Combined with Dual Anti-HER2 Treatment in Early HER2-positive, HR-positive, PIK3CA Mutant Breast Cancer

What this Trial Is About

Researchers are evaluating the potential additional benefits and safety of inavolisib when added to neoadjuvant endocrine therapy for patients with early-stage HER2-positive, HR-positive breast cancer that has a PIK3CA mutation. This phase II study involves patients whose tumors have these specific characteristics and aims to compare the effects of adding inavolisib to a standard treatment regimen. The rationale is to see if inavolisib improves treatment outcomes in this patient group. Participants will be randomly assigned to one of two groups one group will receive neoadjuvant endocrine therapy combined with dual anti-HER2 treatment using a fixed-dose combination of pertuzumab and trastuzumab given subcutaneously every three weeks for six cycles 18 weeks, plus inavolisib taken daily the other group will receive the same endocrine and anti-HER2 therapy without inavolisib. Endocrine therapy may include tamoxifen or an aromatase inhibitor, with or without a GnRH analogue for premenopausal women and men. Treatment continues until surgery, disease progression, unacceptable side effects, or patient withdrawal. After treatment, all patients will undergo surgery or biopsy to assess the complete pathological response. Throughout the study, patients will have physical exams and imaging tests such as sonography, mammography, or MRI to evaluate tumor response. Laboratory tests and cardiac assessments will monitor safety and tolerability. The main outcome measured is the pathologic complete response rate in the breast and lymph nodes approximately 21 weeks after starting treatment. Additional outcomes include safety, response rates, breast conservation rates, and long-term invasive disease-free and overall survival, with follow-up data collected for up to five years. Participation lasts through the treatment period and scheduled assessments.

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