AstraZeneca's PD-L1 Inhibitor Durvalumab Approved in China for Unresectable Stage III NSCLC, Marking a New Era of Immunotherapy

On December 12, AstraZeneca announced that the China National Medical Products Administration (NMPA) has formally approved durvalumab injection (Durvalumab, brand name: Imfinzi), a PD-L1 immune checkpoint inhibitor, for the treatment of patients with unresectable stage III non-small cell lung cancer (NSCLC) who have not experienced disease progression following concurrent chemoradiotherapy with platinum-based chemotherapy. This approval is based on the primary analysis results of progression-free survival (PFS) from the Phase III PACIFIC trial, supported by overall survival (OS) data, with relevant findings published in the New England Journal of Medicine (NEJM).

Results from the PACIFIC clinical trial demonstrated that immunotherapy with durvalumab injection following concurrent chemoradiotherapy reduced the risk of death by nearly 32% in patients with unresectable stage III non-small cell lung cancer (NSCLC). The median progression-free survival (PFS) was 16.8 months, and the 3-year overall survival (OS) rate reached 57%. Durvalumab injection is the first and currently only PD-L1 inhibitor approved in mainland China for the treatment of stage III lung cancer. This approval marks the dawn of a new era of immunotherapy for unresectable stage III NSCLC in China.

Mr. Wang Lei, Executive Vice President of AstraZeneca and President of International Operations and China, stated: “We extend our gratitude to the National Medical Products Administration and relevant authorities for their keen attention to the unmet treatment needs of lung cancer patients and their strong emphasis on facilitating access to innovative therapies. The approval and market launch of durvalumab injection is highly significant, bringing renewed hope to patients with stage III non-small cell lung cancer (NSCLC). It also enables AstraZeneca to better fulfill its commitment of ‘Rooted in China, Serving China,’ benefiting more Chinese lung cancer patients and contributing to the realization of the ‘Healthy China 2030’ goals.”

In the PACIFIC trial, among patients with stage III unresectable non-small cell lung cancer (NSCLC) who did not experience disease progression after platinum-based concurrent chemoradiotherapy, consolidation therapy with durvalumab injection demonstrated statistically and clinically significant improvements in both progression-free survival (PFS) and overall survival (OS) compared with placebo, regardless of PD-L1 expression status. Durvalumab reduced the risk of death by 32% (HR 0.68) and extended median PFS by more than 11 months (median PFS: 16.8 months vs. 5.6 months; HR 0.52).

Professor Wu Yilong, Lifetime Director of Guangdong Provincial People’s Hospital, stated: “The most critical metric for evaluating cancer treatments is whether they enable long-term patient survival and even clinical cure. Stage III lung cancer is a stage with curative potential, and the advent of immunotherapy has offered more patients the opportunity for clinical cure. The PACIFIC trial enrolled patients with unresectable stage III non-small cell lung cancer (NSCLC) who had not progressed after concurrent chemoradiotherapy, comparing the efficacy of consolidation therapy with the PD-L1 inhibitor durvalumab injection versus placebo. The latest reported 3-year survival rate has reached 57%, and the projected 5-year survival rate is expected to exceed 50%. It can be said that durvalumab injection has transformed the treatment paradigm for unresectable stage III NSCLC, representing a revolutionary breakthrough.”

Among patients treated with durvalumab injection, the most common adverse reactions (incidence ≥20%) included cough, fatigue, pneumonitis or radiation pneumonitis, upper respiratory tract infection, dyspnea, and rash. Serious adverse reactions occurred in 29% of patients treated with durvalumab injection, and 15% of patients discontinued treatment due to adverse reactions.

In October 2019, the three-year survival data from the PACIFIC trial were published in the Journal of Thoracic Oncology, with durvalumab injection consistently demonstrating long-term efficacy.1 Professor Wu Yilong stated, “In the NCCN Guidelines, immunotherapy with durvalumab injection following concurrent chemoradiotherapy is listed as the standard of care for stage III lung cancer. Durvalumab injection is currently the only approved immunotherapy indicated for patients with unresectable stage III non-small cell lung cancer (NSCLC) following concurrent chemoradiotherapy. It is hoped that the launch of durvalumab injection in China will bring hope for clinical cure to more Chinese patients with stage III lung cancer.”

Based on the clinical trial data from the PACIFIC study, durvalumab injection has currently been approved in 54 countries and regions worldwide, including the United States, Japan, and Europe, for the treatment of patients with unresectable stage III non-small cell lung cancer (NSCLC) who have potential for clinical cure. The PACIFIC regimen, which involves the use of durvalumab injection following chemoradiotherapy, is globally recognized as the standard of care for unresectable stage III NSCLC.

PACIFIC is a randomized, double-blind, placebo-controlled, international, multicenter Phase III clinical trial designed to evaluate the efficacy of durvalumab injection in patients with unresectable Stage III (locally advanced) non-small cell lung cancer (NSCLC), including both PD-L1-positive and PD-L1-negative populations, who have not progressed following platinum-based concurrent chemoradiotherapy.

This clinical trial was conducted across 235 centers in 26 countries worldwide, enrolling a total of 713 patients. The primary endpoints were progression-free survival (PFS) and overall survival (OS), while the secondary endpoints included landmark analyses of PFS and OS, objective response rate, and duration of response.

Based on the extent of local metastasis and resectability, stage III (locally advanced) non-small cell lung cancer (NSCLC) is typically subdivided into three categories: IIIA, IIIB, and IIIC. Unlike patients with stage IV lung cancer who have already developed distant metastases, those with stage III disease have the potential for clinical cure. The majority of patients with stage III NSCLC are deemed unresectable at the time of diagnosis. Over the past few decades, treatment options for stage III NSCLC have been limited, with concurrent chemoradiotherapy serving as the standard of care, followed by close monitoring of disease progression.

Imfinzi is a human-derived PD-L1 monoclonal antibody that blocks the binding of PD-L1 to PD-1 and CD80, thereby inhibiting tumor immune escape and releasing suppressed immune responses. Imfinzi has been approved in 11 countries and regions worldwide, including the United States, for the treatment of patients with previously treated advanced bladder cancer. As part of new drug development programs, Imfinzi is currently being investigated as a monotherapy or in combination with the CTLA-4 antibody tremelimumab and other novel agents for the treatment of non-small cell lung cancer, small cell lung cancer, bladder cancer, head and neck cancer, liver cancer, cervical cancer, cholangiocarcinoma, and other solid tumors.

AstraZeneca has multiple approved drugs or those in late-stage clinical development, suitable for lung cancer at different stages, treatment phases, and with varying mechanisms of action. We address the unmet treatment needs of patients with EGFR mutation-positive non-small cell lung cancer (NSCLC) through marketed drugs such as gefitinib and osimertinib, ongoing Phase III clinical trials (ADAURA, LAURA, and FLAURA2), and exploratory combination Phase II clinical trials (SAVANNAH and ORCHARD). Approximately 10%-15% of NSCLC patients in Europe and the United States, and about 30%-40% of Asian NSCLC patients, are expected to benefit from these treatments.

Meanwhile, AstraZeneca’s extensive oncology immunotherapy portfolio has also entered late-stage clinical development, targeting patients with lung cancer lacking known genetic mutations, who account for approximately three-quarters of all lung cancer cases. The anti-PD-L1 antibody durvalumab is currently being investigated in studies involving patients with advanced lung cancer (including the Phase III clinical trials POSEIDON, PEARL, and CASPIAN) as well as those with earlier-stage disease with curative intent (including the Phase III clinical trials AEGEAN, ADJUVANT BR.31, PACIFIC-2, PACIFIC-4, PACIFIC-5, and ADRIATIC). These studies evaluate durvalumab as monotherapy or in combination with tremelimumab and/or chemotherapy.

Tumor immunotherapy is a treatment strategy that activates the patient’s immune system to attack tumors. Our portfolio of immunotherapeutic agents is designed to overcome tumor-mediated immunosuppression. For the majority of cancer patients, we believe immunotherapy will offer unprecedented therapeutic opportunities.

For cancer patients with varying types, stages, and treatment histories, we are exploring the use of durvalumab monotherapy or durvalumab in combination with the CTLA-4 antibody tremelimumab, leveraging PD-L1 expression as a predictive biomarker to deliver optimal treatment strategies tailored to different patient populations. Furthermore, our immunotherapy agents, when combined with radiotherapy, chemotherapy, and small-molecule targeted therapies from our company and partners, hold the potential to provide new therapeutic options for a broader range of cancer patients.

AstraZeneca has a long-standing heritage in oncology research. Our rapidly expanding portfolio of novel medicines is transforming patients’ lives and unlocking vast possibilities for the company’s future growth. With at least six new drug approvals between 2014 and 2020, and a robust pipeline enriched by investigational small molecules and biologics, we are committed to establishing oncology as a key growth driver for AstraZeneca. Our research focuses on cancers in four therapeutic areas: lung, ovarian, breast, and hematologic malignancies. In addition to leveraging AstraZeneca’s core capabilities, we actively pursue innovative partnerships and external investments to accelerate our strategy, such as our investment in Acerta Pharma to advance research in hematologic diseases.

By leveraging four major scientific platforms—cancer immunotherapy, tumor driver genes and resistance mechanisms, DNA damage repair, and antibody-drug conjugates—AstraZeneca advocates for the development of personalized combination therapies, aiming to redefine cancer treatment and ultimately conquer cancer in the future.