Roche's PI3Kα Inhibitor Inavolisib Designated for Breakthrough Therapy in China for PIK3CA-Mutant Breast Cancer

▎WuXi AppTec Content Team Report

On March 25, the official website of the Center for Drug Evaluation (CDE) of the China National Medical Products Administration (NMPA) announced that Roche had submitted an application.GDC-0077 (i.e.inavolisib) Proposed for inclusion in the breakthrough therapy category, targeting indications: Combination with palbociclib and endocrine therapy for the treatment ofPIK3CAPatients with mutated, hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative locally advanced or metastatic breast cancer. Publicly available information shows that inavolisib is aSelective inhibitor targeting PI3Kα mutants.Roche recentlyThe 2023 annual report pointed out that the drugExpected to receive regulatory approval in 2024.

Screenshot source:CDE Official Website

Public information shows,PIK3CAGene MutationFound in approximately 40% of HR-positive breast cancers, leading to uncontrolled tumor growth, disease progression, and resistance to endocrine therapy.

Inavolisib is aWith Dual Mechanisms of ActionAn oral therapy with high in vitro PI3Kα inhibitory potency and selectivity, capable of specifically triggering the degradation of PI3Kα protein mutants.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.

In December 2023, Roche announced the combination of inavolisib with the CDK4/6 inhibitor palbociclib and fulvestrant (endocrine therapy),First-line TreatmentPositive Results from Phase 3 Clinical Trial (INAVO120) in Patients with Locally Advanced or Metastatic Breast Cancer.Patients participating in this clinical trialCarryPIK3CAMutation, HR-positive, HER2-negative tumors, and resistance to endocrine therapy。

The test results showed that, compared withPalbociclibCompared with the control group used in combination with fulvestrant,Inavolisib Combination Therapy GroupProgression-Free Survival (PFS) was 15.0 months (7.3 months in the control group), more than doubling the PFS,Reduced the risk of disease progression or death by 57%。This benefit was consistent across different subgroups. Although the overall survival (OS) data are not yet mature, a clear positive trend has been observed. The current data also show clinically meaningful and significant improvements in objective response rate, duration of response, and clinical benefit rate.

▲Clinical Trial Results of Inavolisib for Breast Cancer (Image Source: Reference [2])

According to Roche's recently released 2023 annual report, the company plans to submit these results to regulatory authorities in the hope ofPIK3CAA potential new treatment option for patients with HR+ breast cancer mutations,This is precisely the indication proposed by the CDE to be included in the breakthrough therapy category.Inavolisib is expected to receive regulatory approval in 2024.