Roche's PI3Kα Inhibitor GDC-0077 Receives CDE Approval for Clinical Trial Application in China

The Center for Drug Evaluation (CDE) of China’s National Medical Products Administration (NMPA) has recently announced that GDC-0077, an investigational Class 1 novel drug and a PI3Kα-specific inhibitor developed by Roche, has had its clinical trial application accepted in China. This marks the first time this product has been submitted for clinical trials in China. Globally, it is currently undergoing Phase 3 clinical trials for the treatment of patients with HR-positive, HER2-negative breast cancer. Notably, most PI3K inhibitors under development in China are still in Phase 1 or Phase 2 clinical stages, and no products targeting this pathway have yet been approved for marketing.

GDC-0077 is a PI3Kα-specific inhibitor. It exhibits greater selectivity for PI3Kα and induces the degradation of mutant PI3Kα, thereby producing more potent and durable inhibitory effects. Studies have shown that hyperactivation of the PI3K signaling pathway is significantly correlated with tumor progression, increased tumor microvessel density, and enhanced chemotaxis and invasiveness of cancer cells. Consequently, the PI3K signaling pathway is regarded by researchers as one of the key targets for the development of anticancer therapeutics.

On the ClinicalTrials.gov website, two clinical studies have been registered for GDC-0077. One is a randomized, double-blind, placebo-controlled Phase 3 study evaluating the efficacy and safety of GDC-0077 in combination with the CDK4/6 inhibitor palbociclib and the estrogen receptor antagonist fulvestrant in patients with PIK3CA-mutated, hormone receptor-positive (HR+), HER2-negative locally advanced or metastatic breast cancer. The other is an open-label, dose-escalation Phase 1 study assessing the safety, tolerability, and pharmacokinetics of GDC-0077 as a monotherapy in patients with locally advanced or metastatic PIK3CA-mutated solid tumors, as well as its safety and pharmacokinetics when combined with endocrine and targeted therapies in patients with locally advanced or metastatic PIK3CA-mutated, hormone receptor-positive breast cancer.

According to an early drug development investor event hosted by Genentech, a member of the Roche Group, this February, GDC-0077 demonstrated promising activity in a Phase 2 clinical trial when used in combination with CDK4/6 inhibitors and endocrine therapy for patients with HR-positive, HER2-negative metastatic breast cancer, achieving an overall response rate (ORR) of 52%. Currently, GDC-0077 is undergoing Phase 3 clinical trials for the treatment of patients with HR-positive, HER2-negative breast cancer.

According to statistics, four PI3K inhibitors have been approved for marketing worldwide: Gilead’s idelalisib, Bayer’s copanlisib, Verastem’s duvelisib, and Novartis’ alpelisib (BYL719). However, most PI3K inhibitors under development in China are still in Phase I or Phase II clinical trials, remaining some distance from regulatory approval. Companies pursuing this target include Innovent Biologics, Hutchison China MediTech, Chia Tai Tianqing, and Arno Therapeutics.

This marks the acceptance of GDC-0077’s clinical trial application in China, representing another recent advancement in Roche’s new drug development efforts in the country following the TIGIT inhibitor tiragolumab. We look forward to the smooth progress of this product in subsequent clinical development, so that it may benefit more patients at an early date.

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