3D medical rendering of breast cancer: © Giovanni Cancemi- stock.adobe.com

• The FDA has granted a breakthrough therapy designation to 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 the phase 3 INAVO120 trial (NCT04191499).
• In the trial, the inavolisib regimen more than doubled progression-free survival (PFS) in the first-line setting.

Inavolisib, an investigational, oral treatment, has been granted an FDA breakthrough therapy designation in combination with palbociclib and fulvestrant for the treatment of patients with HR-positive, HER2-negative breast cancer with a PIK3CA mutation.¹

The designation is intended to help accelerate the development and regulatory review of agents that treat serious or life-threatening illnesses.

“We are pleased that the FDA granted breakthrough therapy designation for inavolisib in recognition of the substantial clinical benefit observed with this regimen,” said Levi Garraway, MD, PhD, chief medical officer and head of global product development at Roche, in a press release. “This promising inavolisib-based regimen could transform the PI3K inhibitor class, potentially becoming the standard of care for this patient population in the first-line setting.”

The designation is supported by the phase 3 INAVO120 study. In the study, inavolisib plus palbociclib and fulvestrant reduced the risk of disease progression or death by 57% compared with palbociclib and fulvestrant alone, delivering a 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.

These data will be submitted to global health authorities.

The phase 3 INAVO121(NCT05646862) and INAVO122 (NCT05894239) trials are also investigating inavolisib in PIK3CA-mutated locally advanced or metastatic breast cancer.

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 enrollment. 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 enrollment.

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

REFERENCES:

1. FDA grants breakthrough therapy designation to Roche’s inavolisib for advanced hormone receptor-positive, HER2-negative breast cancer with a PIK3CA mutation. New release. Roche. May 21, 2024. Accessed May 21, 2024. https://tinyurl.com/5f3y45sy

2. A study evaluating the efficacy and safety of inavolisib + palbociclib + fulvestrant vs placebo + palbociclib + fulvestrant in patients with PIK3CA-mutant, hormone heceptor-positive, HER2-negative, locally advanced or metastatic breast cancer (INAVO120). ClinicalTrials.gov. Updated April 26, 2024. Accessed May 21, 2024. https://clinicaltrials.gov/study/NCT04191499