Study of Inavolisib with Trastuzumab and Pertuzumab as Maintenance Therapy in Patients with HER2‑Positive PIK3CA‑Mutated Locally Advanced or Metastatic Breast Cancer

The primary objective of this study is to evaluate the efficacy of inavolisib in combination with Phesgo compared to placebo plus Phesgo as maintenance therapy, based on investigator-assessed progression-free survival (PFS) in patients with HER2-positive, PIK3CA-mutated, locally advanced or metastatic breast cancer. Secondary objectives include the assessment of overall survival (OS), objective response rate (ORR), duration of response (DOR), clinical benefit rate (CBR), and progression-free survival 2 (PFS2). Additionally, the study aims to evaluate health-related quality of life (HRQoL) and functional scores using the EORTC QLQ-C30, monitor safety, and characterize the pharmacokinetics of inavolisib.

This study involves a total of 163 participants diagnosed with HER2-positive, PIK3CA-mutated, locally advanced or metastatic breast cancer. The study population includes both male and female patients within the age ranges corresponding to codes 3 and 4. Eligible individuals must have histologically or cytologically confirmed adenocarcinoma that is not amenable to curative resection. Participants are required to have a disease-free interval of at least 6 months following the completion of adjuvant or neoadjuvant systemic non-hormonal treatment. Key clinical requirements include an Eastern Cooperative Oncology Group Performance Status of 0 or 1 and a left ventricular ejection fraction of at least 50%. Additionally, subjects must demonstrate adequate hematologic and organ function. For the maintenance therapy phase, participants must have completed 4 to 8 cycles of induction therapy and achieved a partial response, complete response, stable disease, or non-CR/non-PD status according to RECIST v1.1.

This Phase III, multicenter, randomized, double-blind, placebo-controlled study evaluates the efficacy and safety of inavolisib in combination with Phesgo versus placebo in combination with Phesgo as maintenance therapy. The research targets individuals with HER2-positive, PIK3CA-mutated, locally advanced or metastatic breast cancer. The methodology involves an initial induction therapy phase consisting of 4 to 8 cycles, followed by randomization to receive either the investigational combination or a placebo. The primary endpoint is investigator-assessed progression-free survival. Secondary objectives include evaluating overall survival, objective response rate, and duration of response, alongside monitoring the incidence of adverse events. Study recruitment is estimated to occur between July 2023 and December 2028.

Inavolisib is an experimental medication administered as a 9 mg film-coated tablet via the oral route.

Phesgo is an experimental treatment consisting of trastuzumab and pertuzumab, provided as a solution for injection for subcutaneous injection at a dose of 1800 mg.

An inavolisib placebo is utilized in the study as a comparator for the experimental medication.

Background therapies may include anhydrous docetaxel, paclitaxel albumin-bound, or paclitaxel administered via intravenous injection, as well as tamoxifen, anastrozole, letrozole, or exemestane administered by the oral route, and goserelin acetate.

The efficacy of the investigational therapy will be evaluated using several parameters. The primary endpoint is investigator assessed progression-free survival (PFS). Secondary endpoints include overall survival (OS), objective response rate (ORR), duration of response (DOR), and clinical benefit rate (CBR). Additionally, PFS 2 will be assessed. The study will measure changes in health-related quality of life (HRQoL) and functional status, specifically through the use of the EORTC QLQ-C30 scales, including the GHS/QoL and functional scales for role and physical domains. Other parameters include changes from baseline in targeted clinical laboratory test results and the plasma concentration of inavolisib at specified timepoints.