Roche's Atezolizumab Nears Approval in China for First-Line Treatment of NSCLC

By Jia Yi

On April 20, the NMPA website showed that the review status of the new indication application for atezolizumab (application number: JXSS2000033) has changed to "under approval," and it may be approved in the near future. This indication is for monotherapy as first-line treatment for patients with metastatic non-small cell lung cancer (NSCLC) who are PD-L1 positive and EGFR/ALK negative.

Atezolizumab is an anti-PD-L1 monoclonal antibody developed by Genentech, a member of the Roche Group. By blocking the interaction between PD-L1 and its receptors PD-1 and B7-1 (also known as CD80), this drug reverses immunosuppression in the tumor microenvironment and T-cell exhaustion, thereby promoting the activation, proliferation, and cytotoxic effects of tumor-specific T cells, ultimately leading to the elimination of tumor cells.

Atezolizumab was first approved in China in February 2020, with the indication of combination with chemotherapy for the first-line treatment of extensive-stage small cell lung cancer (SCLC); in October of the same year, it was also approved in combination with bevacizumab for the first-line treatment of advanced unresectable hepatocellular carcinoma. The current marketing application for first-line treatment of non-small cell lung cancer is the third marketing application for this drug, submitted in September 2020 and officially included in the priority review and approval process in early October.

The Insight database shows that there are currently 36 clinical trials of atezolizumab underway in China, with 23 of them already in Phase III. The indications under investigation cover various types of cancer. In addition to the three indications already approved or submitted for approval in China, the FDA has previously approved T-drug (atezolizumab) for multiple indications including bladder cancer and triple-negative breast cancer.

Source: Insight Database (http://db.dxy.cn/v5/)

The FDA approval of atezolizumab for the first-line treatment of non-small cell lung cancer (NSCLC) was based on the results of the IMpower110 study (ClinicalTrials.gov identifier: NCT02409342). IMpower110 is a randomized, open-label, Phase III clinical trial designed to evaluate the efficacy and safety of atezolizumab as first-line therapy in patients with advanced NSCLC, compared with chemotherapy (cisplatin or carboplatin plus pemetrexed or gemcitabine). The study enrolled a total of 572 treatment-naïve patients without ALK or EGFR gene mutations.

Data presented at the 2019 European Society for Medical Oncology (ESMO) Congress showed that, in patients with high PD-L1 expression, atezolizumab demonstrated a median overall survival (OS) of 20.2 months versus 13.1 months in the chemotherapy group (HR=0.59, 95% CI: 0.40–0.89, p=0.0106), representing a 41% reduction in the risk of death. Updated progression-free survival (PFS), objective response rate (ORR), and duration of response (DoR) data were presented at the 2020 World Conference on Lung Cancer (WCLC): among patients with high PD-L1 expression, the median PFS was 8.2 months for atezolizumab versus 5.0 months for chemotherapy (HR=0.59, 95% CI: 0.43–0.81); the ORRs were 40.2% versus 28.6%, respectively; and the median DoRs were 38.9 months versus 8.3 months, respectively.

High PD-L1 expression is defined as: PD-L1 expression in tumor cells ≥50%, or PD-L1 expression in tumor-infiltrating immune cells ≥10%, or wild-type.

As the only PD-L1 inhibitor currently approved by the FDA as first-line monotherapy for patients with PD-L1-high non-small cell lung cancer (NSCLC), atezolizumab is expected to provide a new treatment option with greater survival benefits for eligible patients in China following its approval for the NSCLC indication in the country.