Promising New Combo Therapy Nears Approval for Advanced Breast Cancer

Introduction to Inavolisib

Inavolisib, also known as GDC-0077, is a novel drug currently under priority review by the FDA for its potential use in treating advanced hormone receptor-positive, HER2-negative breast cancer. The drug has shown promising results, particularly when combined with other treatments, and is targeted at patients with PIK3CA mutations whose cancer has recurred or progressed after initial therapies.

Clinical Trial Insights: INAVO120

The FDA’s decision is backed by data from the phase 3 INAVO120 trial. This significant study evaluated the efficacy of inavolisib combined with palbociclib (Ibrance) and fulvestrant (Faslodex) against a control group receiving only palbociclib and fulvestrant. Results showed a remarkable 57% reduction in the risk of disease progression or death for patients in the inavolisib cohort.

The median progression-free survival (PFS) for patients on inavolisib was 15 months, more than double the 7.3 months observed in the control group. Although overall survival (OS) data was still maturing at the time of analysis, early results indicated a favorable trend for the inavolisib group.

Implications of FDA Priority Review

If approved, inavolisib would become a critical addition to the arsenal of treatments available for this specific subset of breast cancer patients. The FDA has set a target action date of November 27, 2024, highlighting the urgency and importance of delivering this potential treatment option to patients promptly.

The breakthrough therapy designation granted to inavolisib in May 2024 further underscores the significance of this combination therapy. It aims to rapidly advance drugs that show substantial improvement over existing options for serious diseases.

Design and Execution of INAVO120

The INAVO120 trial was meticulously designed as a randomized, double-blind, placebo-controlled study. It involved 325 patients who were carefully selected based on specific criteria, including the presence of PIK3CA mutations and the progression of the disease within 12 months of completing adjuvant endocrine therapy.

Participants were split into two groups: one received oral inavolisib, while the other was given a placebo, in addition to standard treatment with palbociclib and fulvestrant. The primary endpoint was PFS, with secondary endpoints being overall survival, objective response rate, and clinical benefit rate.

Detailed Inclusion and Exclusion Criteria

Key inclusion criteria for the study were measurable disease per RECIST 1.1 criteria, an ECOG performance status of 0 or 1, and a life expectancy of more than six months. This ensured that participants were in relatively good health aside from their cancer diagnosis.

Exclusion criteria included a history of certain other cancers, untreated or active central nervous system metastases, and prior treatment with PI3K, AKT, or mTOR inhibitors. This helped create a more homogeneous study group and reduced potential confounding factors.

Future Prospects and Global Impact

With such promising results, the data from INAVO120 is set to support further regulatory submissions beyond the FDA, including to the European Medicines Agency. A successful approval process could mark a significant breakthrough in advanced breast cancer treatments worldwide.

Inavolisib, if approved, will not only offer a new treatment option but could set a precedent for the development and approval of other combination therapies aimed at specific genetic mutations in cancer patients.

Expert Opinions and Statements

Dr. Levi Garraway, Chief Medical Officer at Genentech, emphasized the transformative potential of inavolisib. He noted that adding inavolisib to standard treatments significantly delayed disease progression, showing potential for extending survival in patients with PIK3CA mutations.

This expert feedback highlights the high level of optimism in the medical community regarding inavolisib’s potential benefits.

Conclusion

The FDA’s priority review of inavolisib combined with palbociclib and fulvestrant marks a significant step towards offering a new, effective treatment for advanced hormone receptor-positive, HER2-negative breast cancer. The promising results from the INAVO120 trial have paved the way for potential approval, providing hope to many affected patients.