Inavolisib Regimen Wins FDA Priority Review for PIK3CA Breast Cancer


Data from the phase 3 INAVO120 trial support the priority review granted by the FDA to inavolisib, palbociclib, and fulvestrant for the treatment of PIK3CA-mutated breast cancer.

3D rendering of tumor in breast tissue: © -

3D rendering of tumor in breast tissue: © -

  • The FDA has granted priority review to the new drug application (NDA) of inavolisib (GDC-0077) plus palbociclib (Ibrance) and fulvestrant for the treatment of hormone receptor (HR)-positive, HER2-negative, PIK3CA-mutated breast cancer.
  • ·The designation is supported by data from the phase 3 INAVO120 trial (NCT04191499).
  • ·The Prescription Drug User Fee Act (PDUFA) target action date is November 27, 2024.

The NDA of inavolisib, an investigational, oral treatment, in combination with palbociclib and fulvestrant for the treatment of patients with HR-positive, HER2-negative breast cancer with a PIK3CA mutation has been granted priority review by the FDA. A PDUFA target action date of November 27, 2024, has been set.1

The priority review designation directs more resources and attention to applications for drugs that would provide significant improvements to the safety or effectiveness of treatments. Roche is also filing submissions with other global health authorities.

The PIK3CA mutation occurs in approximately 40% of HR-positive metastatic breast cancers, highlighting the need for a targeted therapy.

“The addition of inavolisib to standard of care treatment significantly delayed disease progression in the first-line setting and has the potential to extend survival for people with metastatic breast cancers that harbor PIK3CA mutations,” said Levi Garraway, MD, PhD, chief medical officer and head of global product development at Roche, in a press release. “We welcome the FDA’s priority review designation for inavolisib, which underscores the urgency to bring this potential best-in-class treatment option to patients as quickly as possible.”

The priority review is supported by findings from the phase 3 INAVO120 study. In the study, inavolisib plus palbociclib and fulvestrant reduced the risk of disease progression or death by 57% vs palbociclib and fulvestrant alone, delivering a progression-free survival (PFS) of 15.0 months vs 7.3 months, respectively (HR, 0.43; 95% CI, 0.32-0.59; P <.0001). While overall survival (OS) data were not mature at the time of analysis, a positive trend was observed (stratified HR, 0.64; 95% CI, 0.43-0.97; P =.0338), and follow-up for OS will continue.

On May 21, 2024, the FDA granted a breakthrough therapy designation to the regimen in this intent-to-treat population.

About INAVO120

The phase 3, randomized, double-blind, placebo-controlled INAVO120 study enrolled 325 patients with PIK3CA-mutant, HR-positive, HER2 negative, locally advanced or metastatic breast cancer who experienced disease progression during or within 12 months of completing adjuvant endocrine therapy.2

The study’s primary end point is PFS, and secondary end points include objective response rate, best overall response rate, duration of response, clinical benefit rate, time to deterioration (TTD) in pain, TTD in physical function, TTD in role function, TTD in global health status, and incidence of adverse events.

Patients were randomized to receive inavolisib or placebo on days 1 to 28 in combination with palbociclib on days 1 to 21 of a 28-day cycle plus fulvestrant every 4 weeks.

Patients with measurable disease per RECIST v1.1, an ECOG performance status of 0 or 1, a life expectancy of at least 6 months, and adequate hematologic and organ function were eligible for participation. Those with metaplastic breast cancer, history of leptomeningeal disease or carcinomatous meningitis, known or untreated active central nervous system metastases, who received prior systemic therapy for metastatic breast cancer, or who are pregnant or breastfeeding were not eligible for study enrollment.

The study has an anticipated completion date of September 30, 2030.

1. FDA grants priority review to Roche’s inavolisib for advanced hormone receptor-positive, HER2-negative breast cancer with a PIK3CA mutation. News release. Roche. May 29, 2024. Accessed May 29, 2024.
2. A study evaluating the efficacy and safety of inavolisib + palbociclib + fulvestrant vs placebo + palbociclib + fulvestrant in patients with PIK3CA-mutant, hormone receptor-positive, HER2-negative, locally advanced or metastatic breast cancer (INAVO120). Updated April 26, 2024. Accessed May 29, 2024.
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