Roche Secures Six Clinical Trial Approvals in China for TIGIT Inhibitor Tiragolumab and PI3Kα Inhibitor GDC-0077

Latest Public Notice from the Center for Drug Evaluation (CDE) of China’s National Medical Products Administration: Two Innovative Drugs Under Roche Secure Six Clinical Trial Implicit Approvals in China, Namely TIGIT Inhibitor Tiragolumab Injection and PI3Kα Inhibitor GDC-0077. Among them, tiragolumab received four implicit approvals for clinical trials targeting small cell lung cancer, liver cancer, advanced esophageal squamous cell carcinoma, and non-small cell lung cancer indications. The PI3Kα inhibitor obtained two implicit approvals for clinical trials in patients with advanced or metastatic solid tumors, marking its first clinical trial approval in China.

Source: CDE Official Website

1. Tiragolumab Injection: TIGIT Inhibitor

Tiragolumab is a TIGIT immune checkpoint inhibitor under priority development by Roche. TIGIT, which stands for T-cell immunoglobulin and ITIM domain protein, is an immune checkpoint protein expressed in various immune cells, including CD8-positive T cells, CD4-positive T cells, and natural killer (NK) cells. TIGIT serves as a specific negative regulator of the CD226 co-stimulatory receptor, and its expression is significantly associated with T cell exhaustion.

Studies have found that TIGIT is highly expressed in tumor-infiltrating T cells across various cancer types. Furthermore, both PD-1 and TIGIT are expressed in memory T cells with stem-like characteristics, whereas other checkpoint proteins such as LAG-3 and TIM-3 are not expressed in these cells. Therefore, Roche believes that dual targeting of PD-L1 and TIGIT holds promise not only for reversing conventional T cell exhaustion but also for increasing the number of memory T cells with stem-like characteristics, thereby generating more effector T cells and achieving superior tumor-killing efficacy. Currently, Roche is investigating the efficacy of combining tiragolumab with the PD-L1 inhibitor atezolizumab for the treatment of indications including cervical cancer, non-small cell lung cancer, and small cell lung cancer.

In China, tiragolumab has received implied approval for four clinical trials targeting different indications, three of which involve combination therapy with tiragolumab and atezolizumab. The four indications are: ① first-line treatment of extensive-stage small cell lung cancer (ES-SCLC) with tiragolumab in combination with atezolizumab and chemotherapy; ② liver cancer; ③ treatment of unresectable locally advanced esophageal squamous cell carcinoma in patients who have completed definitive concurrent chemoradiotherapy, using tiragolumab in combination with atezolizumab; and ④ treatment of previously untreated, locally advanced, unresectable or metastatic PD-L1-selected non-small cell lung cancer, using tiragolumab in combination with atezolizumab.

Notably, the drug was approved in China just a few days ago for a clinical trial targeting the indication of “combination therapy with atezolizumab for unresectable locally advanced recurrent or metastatic esophageal squamous cell carcinoma.” This means that tiragolumab has received a total of five implied clinical trial approvals in China this week.

2. GDC-0077: PI3Kα Inhibitor

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. Therefore, the PI3K signaling pathway is regarded by researchers as one of the key targets for the development of anticancer therapeutics.

In China, GDC-0077 has received implicit approval for two clinical trials, targeting the indication of "treating patients with unresectable, locally advanced or metastatic solid tumors carrying specific oncogenic alterations or potential predictive biomarkers." Notably, this marks the first time the drug has been approved for clinical use in China.

The ClinicalTrials.gov website shows that GDC-0077 has registered two clinical studies:

One study is a randomized, double-blind, placebo-controlled Phase 3 trial designed to evaluate the efficacy and safety of this product in combination with the CDK4/6 inhibitor palbociclib and the estrogen receptor antagonist fulvestrant in patients with PIK3CA-mutated, hormone receptor-positive, HER2-negative locally advanced or metastatic breast cancer.

Another open-label, dose-escalating Phase 1 study aimed to evaluate 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 to assess the safety, tolerability, and pharmacokinetics of GDC-0077 in combination with endocrine therapy and targeted therapy in patients with locally advanced or metastatic PIK3CA-mutated hormone receptor-positive breast cancer.

Congratulations to Roche on the approval of multiple clinical trial applications for tiragolumab injection and GDC-0077 in China. We hope these studies proceed smoothly and benefit patients at an early date.

References:

[1] Center for Drug Evaluation (CDE), National Medical Products Administration of China. Retrieved Aug 29, 2020, from http://www.cde.org.cn/news.do?method=changePage&pageName=service&frameStr=25

[2]ASCO 20 Roche Analyst Event. Retrieved June 3, 2020, from https://www.roche.com/dam/jcr:f5e7c03b-8c92-4c3d-9279-c966910df429/en/irp20200529.pdf

Original Title: Roche’s TIGIT Inhibitor and PI3Kα Inhibitor Approved for Six Clinical Trials in China, Targeting Multiple Cancers!

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