Genentech Announces Positive OS Results for Itovebi in Advanced HR-Positive Breast Cancer
Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), has announced positive topline results from the Phase III INAVO120 study investigating the combination of Itovebi™ (inavolisib) with palbociclib (Ibrance®) and fulvestrant. This regimen is aimed at treating individuals with PIK3CA-mutated, hormone receptor (HR)-positive, HER2-negative, endocrine-resistant, locally advanced or metastatic breast cancer. These results demonstrate a statistically significant and clinically meaningful overall survival (OS) benefit when the Itovebi-based regimen is compared to palbociclib and fulvestrant alone.
Levi Garraway, M.D., Ph.D., Genentech’s Chief Medical Officer and Head of Global Product Development, stated, “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.”
The OS analysis showed that the Itovebi-based regimen not only delayed disease progression but also improved overall survival for patients with advanced HR-positive, PIK3CA-mutated breast cancer. The positive trend in survival follows the previously reported primary analysis, which demonstrated a 57% reduction in the risk of disease worsening or death when comparing the Itovebi-based regimen to the palbociclib-fulvestrant combination (15.0 months vs. 7.3 months; hazard ratio [HR]=0.43, 95% CI: 0.32-0.59, p<0.001). While OS data were immature at the time of the primary analysis, the results showed a promising trend (stratified HR=0.64, 95% CI: 0.43-0.97, p=0.0338). Importantly, no new safety concerns were observed.
The complete OS results will be presented at an upcoming medical meeting, and they further validate the potential of the Itovebi regimen in improving survival outcomes in this patient population. In October 2024, the U.S. Food and Drug Administration (FDA) approved the Itovebi-based regimen for treating adults with endocrine-resistant, PIK3CA-mutated, HR-positive, HER2-negative, locally advanced or metastatic breast cancer who have experienced recurrence after adjuvant endocrine therapy. This regimen, following approval, is now being reviewed by global health authorities, including the European Medicines Agency (EMA).
The positive results from INAVO120 build on earlier findings published in the New England Journal of Medicine, strengthening the rationale for broader clinical use. The study is one of four ongoing Phase III trials (INAVO120, INAVO121, INAVO122, INAVO123) sponsored by Genentech, each exploring different combinations of Itovebi for PIK3CA-mutated locally advanced or metastatic breast cancer. Genentech is also exploring further studies across various tumor types to expand the therapeutic potential of this targeted therapy.
About the INAVO120 Study
The INAVO120 study (NCT04191499) is a Phase III, randomized, double-blind, placebo-controlled trial designed to assess the efficacy and safety of Itovebi in combination with palbociclib and fulvestrant. The trial included 325 patients with PIK3CA-mutated, HR-positive, HER2-negative, locally advanced or metastatic breast cancer, whose disease had progressed during treatment or within 12 months of completing adjuvant endocrine therapy. These participants had not previously received systemic therapy for metastatic disease.
The primary endpoint of the study was progression-free survival (PFS), defined as the time from randomization to disease progression or death from any cause. Secondary endpoints included overall survival (OS), objective response rate, and clinical benefit rate.
Additionally, Genentech is investigating the combination of Itovebi with other therapies in the treatment of HR-positive/HER2-negative breast cancer:
- INAVO121: Combination of Itovebi with fulvestrant versus alpelisib plus fulvestrant in HR-positive/HER2-negative breast cancer after treatment with cyclin-dependent kinase 4/6 (CDK4/6) inhibitors and endocrine therapy.
- INAVO122: Combination of Itovebi with dual HER2 blockade versus dual HER2 blockade with optional endocrine therapy for HER2-positive disease.
- INAVO123: Combination of Itovebi with CDK4/6 inhibitors and letrozole versus placebo plus CDK4/6 inhibitors and letrozole for first-line treatment in endocrine-sensitive, PIK3CA-mutated HR-positive/HER2-negative breast cancer.
Understanding Hormone Receptor-Positive (HR-Positive) Breast Cancer
Hormone receptor-positive breast cancer is the most common subtype of breast cancer, representing about 70% of all cases. These cancers are characterized by tumor cells that have receptors for hormones such as estrogen or progesterone, which can promote tumor growth. Patients with HR-positive metastatic breast cancer often face the risk of disease progression and significant treatment side effects, highlighting the need for better treatment options. The PI3K pathway, which is frequently disrupted in HR-positive breast cancer, particularly due to mutations in the PIK3CA gene, is an important mechanism of resistance to endocrine therapy and CDK4/6 inhibitors.
What is Itovebi?
Itovebi (inavolisib) is a prescription medication used in combination with palbociclib and fulvestrant to treat adults with HR-positive, HER2-negative breast cancer that is PIK3CA-mutated and has advanced to locally advanced or metastatic stages. This combination is specifically indicated for cases that have recurred following hormone therapy. Before starting treatment, patients undergo testing to ensure they have the appropriate PIK3CA mutation.
Safety Information
Itovebi may cause serious side effects, such as hyperglycemia (high blood sugar), mouth sores, and diarrhea. Patients are closely monitored for blood sugar levels before and during treatment. Other common side effects include decreases in white blood cells, red blood cells, platelets, and changes in electrolytes. Additionally, Itovebi may affect fertility, and its safety during pregnancy and breastfeeding is not established.
Patients should inform their healthcare provider about all medical conditions and medications, including any history of diabetes or kidney problems.
Genentech’s Commitment to Breast Cancer Research
Genentech has been advancing breast cancer research for over three decades, aiming to provide effective treatments for all breast cancer subtypes, including HER2-positive and triple-negative forms. As part of its ongoing efforts, Genentech is identifying new biomarkers and exploring innovative treatments for estrogen receptor-positive breast cancer.
About Genentech
Genentech is a leading biotechnology company that discovers, develops, manufactures, and commercializes medicines for patients with serious medical conditions. Headquartered in South San Francisco, California, Genentech is a member of the Roche Group. For more information, visit www.gene.com.
Note: This article is based on the information provided in Genentech’s release and public medical sources. Please consult a healthcare provider for personal medical advice.
