▎WuXiEdited by Kant Content Team

Roche announced today that the U.S. FDA has accepted its New Drug Application (NDA) for the investigational, potentially "best-in-class" oral small molecule inavolisib in combination with the CDK4/6 inhibitor Ibrance (palbociclib) and fulvestrant, granting it Priority Review status for the treatment of tumors withPIK3CAMutations, hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative locally advanced or metastatic breast cancer in adult patients who experience recurrence within 12 months after completing adjuvant endocrine therapy. The FDA is expected to complete the review by November 27, 2024.

Regulatory Applications for Inavolisib Combination TherapyMainly based on the positive results of the INAVO120 Phase 3 clinical trial.This trial is a randomized, double-blind, placebo-controlled study designed to evaluate inavolisib in combination with Ibrance and fulvestrant compared to placebo plus Ibrance and fulvestrant in the treatment.PIK3CAEfficacy and safety in patients with mutant, HR-positive, HER2-negative locally advanced or metastatic breast cancer, who experienced disease progression during treatment or within 12 months after completing adjuvant endocrine therapy, and have not received systemic therapy for treating metastatic tumors.The study enrolled 325 patients, with the primary endpoint being investigator-assessed progression-free survival (PFS), defined as the time from randomization to disease progression or death from any cause.Secondary endpoints include overall survival, objective response rate, and clinical benefit rate.

▲Trial results of Inavolisib for breast cancer treatment (Image source: Reference [2])

The analysis shows,Compared with the control group (PFS=7.3 months), the inavolisib combination therapy (PFS=15.0 months) reduced the risk of disease progression or death by 57% (HR=0.43, 95% CI: 0.32-0.59, p<0.0001).The overall survival data is not yet mature, but a significant positive trend has been observed (stratified HR=0.64, 95% CI: 0.43-0.97, p=0.0338).Follow-up for overall survival will continue until the next analysis. Data from the INAVO120 trial are also being submitted to other global regulatory authorities, including the European Medicines Agency (EMA).

Inavolisib combination therapy was well tolerated, with adverse events consistent with the known safety profile from previous studies, and no new safety signals were observed.

Inavolisib is an oral therapy with high in vitro potency and selectivity for PI3Kα inhibition, capable of specifically triggering the degradation of mutant PI3Kα proteins.Through this unique dual mechanism of action, inavolisib may provide a new treatment option for HR-positive/HER2-negative,PIK3CAPatients with advanced breast cancer mutations provide well-tolerated, durable disease control and potentially improved outcomes. Approximately 40% of HR-positive breast cancer patients carryPIK3CAGene mutation, which may lead to uncontrolled tumor growth, disease progression, and resistance to endocrine therapy.

References:

[1] FDA grants Priority Review to Roche’s inavolisib for advanced hormone receptor-positive, HER2-negative breast cancer with a PIK3CA mutation. Retrieved May 29, 2024 from https://www.roche.com/media/releases/med-cor-2024-05-29

[2] Rche Reporting，Retrieved May 29, 2024 from https://assets.roche.com/f/176343/x/ac48d3ba3b/irp240201-a.pdf

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