Updated INAVO120 Trial Data Show Overall Survival Improvement with Itovebi Combination in Certain Type of Advanced Breast Cancer

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Updated findings from the Phase III INAVO120 trial (NCT04191499) show that the combination of Itovebi (inavolisib) plus Ibrance (palbociclib) and Faslodex (fulvestrant) produced a significant improvement in overall survival (OS) among patients with PIK3CA-mutated, HR-positive, HER2-negative, endocrine-resistant, locally advanced or metastatic breast cancer.^1,2 The statistically significant and clinically meaningful OS improvement achieved the trial’s key secondary endpoint, following earlier data from the trial that found the Itovebi combination significantly improved progression-free survival (PFS), which was the trial’s primary endpoint.

"The INAVO120 overall survival results show that the Itovebi-based regimen not only delayed disease progression, but also helped people with advanced HR-positive, PIK3CA-mutated breast cancer live longer,” Levi Garraway, MD, PhD, Roche chief medical officer, head of Global Product Development, said in a press release. “These findings underscore our ambition to improve survival rates for people with breast cancer. The Itovebi-based regimen has the potential to become the new standard of care for these patients.”¹

Itovebi is a highly potent and selective inhibitor of the alpha isoform of the p110 catalytic subunit of the PI3K complex. The oral targeted therapy has demonstrated best-in-class potential, with a manageable safety profile and durable disease control in this patient population, who often have a poor prognosis and lack effective treatment options. In October 2024, the FDA approved the combination of Itovebi with Ibrance and Faslodex for this indication.³

Trial Design

INAVO120 is a double-blind, randomized trial evaluating first-line Itovebi administered orally at a dose of 9 mg once daily plus Ibrance and Faslodex compared to placebo plus Ibrance and Faslodex in patients with PIK3CA-mutated, HR–positive, HER2–negative locally advanced or metastatic breast cancer with disease that relapsed during or within 12 months after completing adjuvant endocrine therapy. The trial’s primary endpoint was investigator-assessed PFS, with secondary endpoints including OS, objective response rate, clinical benefit rate, response duration, and patient-reported outcomes.

Eligibility criteria included being premenopausal, perimenopausal, or postmenopausal with PIK3CA-mutated, hormone receptor–positive, HER2-negative locally advanced or metastatic breast cancer. Other criteria included having a fasting glucose level of under 126 mg per deciliter, glycated hemoglobin level under 6.0%, and measurable disease as per Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1.

A total of 325 patients in 28 countries were randomly assigned in a 1:1 ratio to either the Itovebi cohort (n = 161) or the placebo cohort (n = 164). Data released in October 2024 and published in The New England Journal of Medicine (NEJM) found patients administered the Itovebi combination achieved a median PFS of 15.0 months (95% confidence interval [CI], 11.3 to 20.5) compared to 7.3 months (95% CI, 5.6 to 9.3) in the placebo group (hazard ratio for disease progression or death, 0.43; 95% CI, 0.32 to 0.59; P<0.001). An objective response was shown in 58.4% of patients in the Itovebi combination group compared to 25.0% of patients in the placebo group.⁴

Full OS results will be presented at an upcoming medical meeting, according to Roche. No new safety signals were reported in the updated findings.

There are currently four Phase III clinical trials analyzing various Itovebi combinations in the treatment of PIK3CA-mutated locally advanced or metastatic breast cancer: INAVO120, INAVO121, INAVO122, INAVO123.

“The landmark survival analysis showed that the probability of death by 6 months was 10.1% in the placebo group and 2.7% in the inavolisib group, which emphasizes the importance of administering inavolisib plus palbociclib–fulvestrant to this patient population as a first-line therapy,” the study authors wrote in NEJM. “Our trial showed that inavolisib can be combined with a CDK4/6 inhibitor and endocrine therapy at the full dose of each drug with an acceptable safety level and side-effect profile.”⁴

References

1. Roche’s Itovebi demonstrated statistically significant and clinically meaningful overall survival benefit in a certain type of HR-positive advanced breast cancer. News release. Roche. January 27, 2025. Accessed January 28, 2025. https://www.roche.com/media/releases/med-cor-2025-01-28

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). ClinicalTrials.gov. Updated October 9, 2024. Accessed January 28, 2025. https://clinicaltrials.gov/study/NCT04191499

3. FDA Approves Genentech’s Itovebi, a Targeted Treatment for Advanced Hormone Receptor-Positive, HER2-Negative Breast Cancer With a PIK3CA Mutation. Genentech. October 10, 2024. Accessed January 28, 2025. https://www.gene.com/media/press-releases/15039/2024-10-10/fda-approves-genentechs-itovebi-a-target

4. Turner N., et al. Inavolisib-Based Therapy in PIK3CA-Mutated Advanced Breast Cancer. Published October 30, 2024. N Engl J Med 2024;391:1584-1596. DOI: 10.1056/NEJMoa2404625. VOL. 391 NO. 17.